| |  | | | | | We just completed performing emergency maintenance on Feed My Inbox. All emails were delayed during this time. We appreciate your patience and are so sorry for any inconvenience this may have caused. | | | | | | | | | | | | |  | |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | Here is a brief look at the letters of interest submitted to the board of the $3 billion California stem cell agency by two men in pursuit of a six-year appointment as its new chairman. First the item on Jonathan Thomas, then Frank Litvack. CIRM directors begin evaluating the men on Monday.
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Bond financier Jonathan Thomas says he would liquidate his holdings in Advanced Cell Technology of | | | | | | | | | | | | | | | | | | | | | | | | | Activin/Nodal Signalling Controls Divergent Transcriptional Networks in Human Embryonic Stem Cells and in Endoderm Progenitors. Stem Cells. 2011 May 31; Authors: Brown S, Teo A, Pauklin S, Hannan N, Cho CH, Lim B, Vardy L, Dunn RN, Trotter MW, Pedersen R, Vallier L Activin/Nodal signalling is necessary to maintain pluripotency of human Embryonic Stem Cells (hESCs) and to induce their differentiation towards endoderm. However, the mechanisms by which Activin/Nodal signalling achieves these opposite functions remain unclear. To unravel these mechanisms, we examined the transcriptional network controlled in hESCs by Smad2 and Smad3 which represent the direct effectors of Activin/Nodal signalling. These analyses reveal that Smad2/3 participate in the control of the core transcriptional network characterising pluripotency which includes Oct-4, Nanog, FoxD3, Dppa4, Tert, Myc and UTF-1. In addition, similar experiments performed on endoderm cells confirm that a broad part of the transcriptional network directing differentiation is downstream of Smad2/3. Therefore, Activin/Nodal signalling appears to control divergent transcriptional networks in hESCs and in endoderm. Importantly, we observed an overlap between the transcriptional network downstream of Nanog and Smad2/3 in hESCs while functional studies showed that both factors cooperate to control the expression of pluripotency genes. Therefore, the effect of Activin/Nodal signalling on pluripotency and differentiation could be dictated by tissue specific Smad2/3 partners such as Nanog, explaining the mechanisms by which signalling pathways can orchestrate divergent cell fate decisions. PMID: 21630377 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Cutting edge on research of cartilage metabolism. Transcriptional Regulation of Osteoarthritis.] Clin Calcium. 2011;21(6):853-859 Authors: Saito T, Kawaguchi H Osteoarthritis (OA) is one of the most common skeletal disorders characterized by cartilage degradation ; however, little was known about the underlying molecular mechanism. Several experimental OA models in mice by producing instability in the knee joints have been developed, and many molecules and signals have been shown to be involved with OA progression through in vivo analyses using mouse OA models. Recently we identified hypoxia-inducible factor-2α (HIF2A) as an extensive regulator of the endochondal ossification process. We have shown that HIF2A, which is induced by the NF-κB signal, controls OA progression by inducing various target molecules. PMID: 21628800 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Chemical control of FGF-2 release for promoting calvarial healing with adipose stem cells. J Biol Chem. 2011 Apr 1;286(13):11307-13 Authors: Kwan MD, Sellmyer MA, Quarto N, Ho AM, Wandless TJ, Longaker MT Chemical control of protein secretion using a small molecule approach provides a powerful tool to optimize tissue engineering strategies by regulating the spatial and temporal dimensions that are exposed to a specific protein. We placed fibroblast growth factor 2 (FGF-2) under conditional control of a small molecule and demonstrated greater than 50-fold regulation of FGF-2 release as well as tunability, reversibility, and functionality in vitro. We then applied conditional control of FGF-2 secretion to a cell-based, skeletal tissue engineering construct consisting of adipose stem cells (ASCs) on a biomimetic scaffold to promote bone formation in a murine critical-sized calvarial defect model. ASCs are an easily harvested and abundant source of postnatal multipotent cells and have previously been demonstrated to regenerate bone in critical-sized defects. These results suggest that chemically controlled FGF-2 secretion can significantly increase bone formation by ASCs in vivo. This study represents a novel approach toward refining protein delivery for tissue engineering applications. PMID: 21262969 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Engineering Biomaterial Systems to Enhance Viral Vector Gene Delivery. Mol Ther. 2011 May 31; Authors: Jang JH, Schaffer DV, Shea LD Integrating viral gene delivery with engineered biomaterials is a promising strategy to overcome a number of challenges associated with virus-mediated gene delivery, including inefficient delivery to specific cell types, limited tropism, spread of vectors to distant sites, and immune responses. Viral vectors can be combined with biomaterials either through encapsulation within the material or immobilization onto a material surface. Subsequent biomaterial-based delivery can increase the vector's residence time within the target site, thereby potentially providing localized delivery, enhancing transduction, and extending the duration of gene expression. Alternatively, physical or chemical modification of viral vectors with biomaterials can be employed to modulate the tropism of viruses or reduce inflammatory and immune responses, both of which may benefit transduction. This review describes strategies to promote viral gene delivery technologies using biomaterials, potentially providing opportunities for numerous applications of gene therapy to inherited or acquired disorders, infectious disease, and regenerative medicine. PMID: 21629221 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stem cells: clinical trials results the end of the beginning or the beginning of the end? Cardiovasc Hematol Disord Drug Targets. 2010 Sep 1;10(3):186-201 Authors: Behfar A, Crespo-Diaz R, Nelson TJ, Terzic A, Gersh BJ With increasing focus on the advance towards curative solutions, it is hard not to be excited by the potential of stem cell-based therapy. Application of the stem cell paradigm to cardiovascular medicine has fostered the evolution of novel approaches aimed at reversing injury caused by ischemic and non-ischemic cardiomyopathy. The feasibility and safety of stem cell use has been established in over 3,000 patients with either recent myocardial infarction or chronic organ failure. Nonetheless, the efficacy of stem cell therapy continues to remain in question. Initial clinical trials have focused on evaluation of multiple adult stem cell phenotypes in their unaltered, naíve state as a "first generation" resource for repair. Though significant strides in perfecting delivery of these biologics to the diseased heart have been achieved, the benefits with regard to myocardial functional recovery have been modest at best. One approach towards optimizing outcome may lie upon preemptive guidance of stem cells down the pathway of myocyte regeneration. As seen with pharmacotherapeutics in the last century, successful translation of "second generation" biotherapeutics in the 21(st) century will require close integration of a community of practice and science to ensure broad application of this emerging technology in the treatment of heart disease. PMID: 20678060 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Tissue engineering-based cartilage repair with mesenchymal stem cells in a porcine model. J Orthop Res. 2011 May 31; Authors: Chang CH, Kuo TF, Lin FH, Wang JH, Hsu YM, Huang HT, Loo ST, Fang HW, Liu HC, Wang WC This in vivo pilot study explored the use of mesenchymal stem cell (MSC) containing tissue engineering constructs in repair of osteochondral defects. Osteochondral defects were created in the medial condyles of both knees of 16 miniature pigs. One joint received a cell/collagen tissue engineering construct with or without pretreatment with transforming growth factor β (TGF-β) and the other joint from the same pig received no treatment or the gel scaffold only. Six months after surgery, in knees with no treatment, all defects showed contracted craters; in those treated with the gel scaffold alone, six showed a smooth gross surface, one a hypertrophic surface, and one a contracted crater; in those with undifferentiated MSCs, five defects had smooth, fully repaired surfaces or partially repaired surfaces, and one defect poor repair; in those with TGF-β-induced differentiated MSCs, seven defects had smooth, fully repaired surfaces or partially repaired surfaces, and three defects showed poor repair. In Pineda score grading, the group with undifferentiated MSC, but not the group with TGF-β-induced differentiated MSCs, had significantly lower subchondral, cell morphology, and total scores than the groups with no or gel-only treatment. The compressive stiffness was larger in cartilage without surgical treatment than the treated area within each group. In conclusion, this preliminary pilot study suggests that using undifferentiated MSCs might be a better approach than using TGF-β-induced differentiated MSCs for in vivo tissue engineered treatment of osteochondral defects. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. PMID: 21630328 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Minimally invasive management of dental caries: Contemporary teaching of posterior resin-based composite placement in U.S. and Canadian dental schools. J Am Dent Assoc. 2011 Jun;142(6):612-20 Authors: Lynch CD, Frazier KB, McConnell RJ, Blum IR, Wilson NH Resin-based composites are an increasingly popular material for restoring posterior teeth, permitting minimally invasive cavity preparations and esthetic restorations. The authors investigated current teaching of the placement of posterior resin-based composites in U.S. and Canadian dental schools. PMID: 21628682 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Cutting edge on research of cartilage metabolism. Transcriptional Regulation of Osteoarthritis.] Clin Calcium. 2011;21(6):853-859 Authors: Saito T, Kawaguchi H Osteoarthritis (OA) is one of the most common skeletal disorders characterized by cartilage degradation ; however, little was known about the underlying molecular mechanism. Several experimental OA models in mice by producing instability in the knee joints have been developed, and many molecules and signals have been shown to be involved with OA progression through in vivo analyses using mouse OA models. Recently we identified hypoxia-inducible factor-2α (HIF2A) as an extensive regulator of the endochondal ossification process. We have shown that HIF2A, which is induced by the NF-κB signal, controls OA progression by inducing various target molecules. PMID: 21628800 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cellular adhesion on collagen: a simple method to select human basal keratinocytes which preserves their high growth capacity. Eur J Dermatol. 2011 May 1;21(1):12-20 Authors: Fortunel NO, Chadli L, Bourreau E, Cadio E, Vaigot P, Marie M, Deshayes N, Rathman-Josserand M, Leclaire J, Martin MT The regenerative capacity of human interfollicular epidermis is closely linked to the potential of immature keratinocytes present within its basal layer. The availability of selection methods and culture systems allowing precise assessment of basal keratinocyte characteristics is critical for increasing our knowledge of this cellular compartment. This report presents a multi-parametric comparative study of basal keratinocytes selected according to two different principles: 1) high adhesion capacity on a type-I collagen-coated substrate [Adh(+++)], 2) high cell-surface expression of α6-integrin [Itg-α6 (high)]. Importantly, analysis performed at the single-cell level revealed similar primary clone-forming efficiency values of 45.5% ± 6.7% [Itg-α6(high)] and 43.7% ± 7.4% [Adh(+++)], which were markedly higher than those previously reported. In addition, both methods selected keratinocytes exhibiting an extensive long-term growth potential exceeding 100 cell doublings and the capacity for generating a pluristratified epidermis. Our study also included a global transcriptome comparison. Genome-wide profiling indicated a strong similarity between [Adh(+++)] and [Itg-α6(high)] keratinocytes, and revealed a common basal-associated transcriptional signature. In summary, cross-analysis of [Adh(+++)] and [Itg-α6(high)] keratinocyte characteristics showed that these criteria identified highly equivalent cellular populations, both characterized by unexpectedly high growth capacities. These results may have broad impacts in the tissue engineering and cell therapy fields. PMID: 21628125 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Spatial control of gene expression within a scaffold by localized inducer release. Biomaterials. 2011 Apr;32(11):3062-71 Authors: Baraniak PR, Nelson DM, Leeson CE, Katakam AK, Friz JL, Cress DE, Hong Y, Guan J, Wagner WR Gene expression can be controlled in genetically modified cells by employing an inducer/promoter system where presence of the inducer molecule regulates the timing and level of gene expression. By applying the principles of controlled release, it should be possible to control gene expression on a biomaterial surface by the presence or absence of inducer release from the underlying material matrix, thus avoiding alternative techniques that rely upon uptake of relatively labile DNA from material surfaces. To evaluate this concept, a modified ecdysone-responsive gene expression system was transfected into B16 murine cells and the ability of an inducer ligand, which was released from elastomeric poly(ester urethane) urea (PEUU), to initiate gene expression was studied. The synthetic inducer ligand was first loaded into PEUU to demonstrate extended release of the bioactive molecule at various loading densities over a one year period in vitro. Patterning films of PEUU variably-loaded with inducer resulted in spatially controlled cell expression of the gene product (green fluorescent protein, GFP). In porous scaffolds made from PEUU by salt leaching, where the central region was exclusively loaded with inducer, cells expressed GFP predominately in the loaded central regions whereas expression was minimal in outer regions where ligand was omitted. This scaffold system may ultimately provide a means to precisely control progenitor cell commitment in a spatially-defined manner in vivo for soft tissue repair and regeneration. PMID: 21269687 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Bone Regeneration: Current Concepts and Future Directions. BMC Med. 2011 May 31;9(1):66 Authors: Dimitriou R, Jones E, McGonagle D, Giannoudis PV ABSTRACT: Bone regeneration is a complex well-orchestrated physiological process of bone formation seeing during normal fracture healing or continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities; or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or "insufficient" bone regeneration process, including the "gold standard" autologous bone graft, free fibula vascularised graft, allograft implantation, the use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved "local" strategies in terms of tissue engineering and gene therapy, or even "systemic" enhancement of bone repair are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone grafts substitutes with bio-mechanical properties as identical to normal bone as possible, to accelerate the overall regeneration process or even to address systemic conditions, such as skeletal disorders and osteoporosis. PMID: 21627784 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cellular and extracellular programming of cell fate through engineered intracrine-, paracrine-, and endocrine-like mechanisms. Biomaterials. 2011 Apr;32(11):3053-61 Authors: Sarkar D, Ankrum JA, Teo GS, Carman CV, Karp JM A cell's fate is tightly controlled by its microenvironment. Key factors contributing to this microenvironment include physical contacts with the extracellular matrix and neighboring cells, in addition to soluble factors produced locally or distally. Alterations to these cues can drive homeostatic processes, such as tissue regeneration/wound healing, or may lead to pathologic tissue dysfunction. In vitro models of cell and tissue microenvironments are desirable for enhanced understanding of the biology and ultimately for improved treatment. However, mechanisms to exert specific control over cellular microenvironments remains a significant challenge. Genetic modification has been used but is limited to products that can be manufactured by cells and release kinetics of therapeutics cannot easily be controlled. Herein we describe a non-genetic approach to engineer cells with an intracellular depot of phenotype altering agent/s that can be used for altering cell fate via intracrine-, paracrine-, and endocrine-like mechanisms. Specifically, we show that human mesenchymal stem cells (MSCs) can be engineered with poly lactide-co-glycolic acid (PLGA) particles containing dexamethasone, which acts on cytoplasmic receptors. The controlled release properties of these particles allowed for sustained intracellular and extracellular delivery of agent to promote differentiation of particle-carrying cells, as well as neighboring cells and distant cells that do not contain particles. PMID: 21262537 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Adipose tissue-derived stem cells display a proangiogenic phenotype on 3D scaffolds. J Biomed Mater Res A. 2011 May 31; Authors: Neofytou EA, Chang E, Patlola B, Joubert LM, Rajadas J, Gambhir SS, Cheng Z, Robbins RC, Beygui RE Ischemic heart disease is the leading cause of death worldwide. Recent studies suggest that adipose tissue-derived stem cells (ASCs) can be used as a potential source for cardiovascular tissue engineering due to their ability to differentiate along the cardiovascular lineage and to adopt a proangiogenic phenotype. To understand better ASCs' biology, we used a novel 3D culture device. ASCs' and b.END-3 endothelial cell proliferation, migration, and vessel morphogenesis were significantly enhanced compared to 2D culturing techniques. ASCs were isolated from inguinal fat pads of 6-week-old GFP+/BLI+ mice. Early passage ASCs cells (P3-P4), PKH26-labeled murine b.END-3 cells or a co-culture of ASCs and b.END-3 cells were seeded at a density of 1 × 10(5) on three different surface configurations: (a) a 2D surface of tissue culture plastic, (b) Matrigel, and (c) a highly porous 3D scaffold fabricated from inert polystyrene. VEGF expression, cell proliferation, and tubulization, were assessed using optical microscopy, fluorescence microscopy, 3D confocal microscopy, and SEM imaging (n = 6). Increased VEGF levels were seen in conditioned media harvested from co-cultures of ASCs and b.END-3 on either Matrigel or a 3D matrix. Fluorescence, confocal, SEM, bioluminescence revealed improved cell, proliferation, and tubule formation for cells seeded on the 3D polystyrene matrix. Collectively, these data demonstrate that co-culturing ASCs with endothelial cells in a 3D matrix environment enable us to generate prevascularized tissue-engineered constructs. This can potentially help us to surpass the tissue thickness limitations faced by the tissue engineering community today. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2011. PMID: 21630430 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | 4'-Hydroxycinnamaldehyde from Alpinia galanga (Linn.) Induces Human Leukemic Cell Apoptosis via Mitochondrial and Endoplasmic Reticulum Stress Pathways. Asian Pac J Cancer Prev. 2011;12(3):593-8 Authors: Banjerdpongchai R, Punyati P, Nakrob A, Pompimon W, Kongtawelert P Rhizomes of Alpinia galanga (Linn.) or 'Kha' in Thai are used in food and as folk medicine in South and Southeast Asia. The aims of this study were to identify the mechanism of cell death of human leukemic HL-60 and U937 cells induced by 4'-hydroxycinnamaldehyde (4'-HCA) isolated from A. galanga. 4'-HCA was cytotoxic to both cell lines in a dose-dependent manner (p<0.05) as demonstrated by MTT assay. Apoptosis induced by 4'-HCA was demonstrated by a variety of methods: visualization of propidium iodide (PI)-stained cells under fluorescence microscope, detection of subdiploid cells by PI-staining and flow cytometry, and assay of active caspase-3 using a specific fluorogenic substrate. 4'-HCA-treated cells (10 and 50 ?g/ml for 4 h) showed significant increase in reactive oxygen species production and decreased mitochondrial transmembrane potential as detected by dichlorohydrofluorescein diacetate and 3,3'-dihexyloxacarbocyanine iodide respectively, together with flow cytometry. The apoptotic death involved cytochrome c release, increase in Bax level and concomitant decreases in levels of Bcl-2 and Bcl-xL (using Western blotting), and elevation in cytosolic and mitochondrial Ca2+ contents (using compartment-specific fluorescent Ca2+ dyes). These results indicate that 4'-HCA induces apoptosis of human leukemic cell through a combination of mitochondrial and ER stress pathways. PMID: 21627350 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Surface modification with peptide for enhancing chondrocyte adhesion and cartilage regeneration in porous scaffolds. Colloids Surf B Biointerfaces. 2011 May 1;84(1):63-70 Authors: Kuo YC, Wang CC The present study presents the regeneration of cartilage in hybrid scaffolds comprising polyethylene oxide (PEO) and chitosan with surface CDPGYIGSR. This surface peptide was grafted via crosslinking onto the scaffolds. The pores in the scaffolds were interconnected and uniformly distributed with an average diameter about 200-250 μm. A high weight percentage of PEO in the matrix yielded a rugged topography of the pore surfaces. The adhesion of bovine knee chondrocytes (BKCs) in the peptide-grafted scaffolds was more efficient than that in the peptide-free scaffolds. In addition, the constructs with surface peptide could stimulate chondrogenesis with enhanced quantities of BKCs, glycosaminoglycans (GAGs), and collagen over cultivation. The histological staining of the proliferated BKCs and secreted GAGs indicated that the surface peptide favored the production of neocartilage in the constructs. Moreover, the immunochemical staining against type II collagen demonstrated the maintenance of phenotypic chondeocytes on the peptide-grafted surfaces. The peptide-grafted PEO/chitosan scaffolds can be applied to the treatment for injured cartilage in preclinical trials. PMID: 21227663 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | An injectable vehicle for nucleus pulposus cell-based therapy. Biomaterials. 2011 Apr;32(11):2862-70 Authors: Collin EC, Grad S, Zeugolis DI, Vinatier CS, Clouet JR, Guicheux JJ, Weiss P, Alini M, Pandit AS An injectable hydrogel, acting as a reservoir for cell delivery and mimicking the native environment, offers promise for nucleus pulposus (NP) repair and regeneration. Herein, the potential of a stabilised type II collagen hydrogel using poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-StarPEG) cross-linker, enriched with hyaluronic acid (HA) was investigated. The optimally stabilised type II collagen hydrogel was determined by assessing free amine groups, resistance to enzymatic degradation, gel point. The potential toxicity of the cross-linker was initially assessed against adipose-derived stem cells (ADSCs). After addition of HA (molar ratio type II collagen:HA 9:0, 9:1, 9:4.5, 9:9) within the hydrogel, the behaviour of the encapsulated NP cells was evaluated using cell proliferation assay, gene expression analysis, cell distribution and cell morphology. A significant decrease (p < 0.05) in the free amine groups of collagen was observed, confirming successful cross-linking. Gelation was independent of the concentration of 4S-StarPEG (8 min at 37 °C). The 1 mm cross-linked hydrogel yielded the most stable after enzymatic degradation (p < 0.05). No toxicity of the 4S-StarPEG was noted for the ADSCs. NP cell viability was high regardless of the concentration of HA (>80%). A cell proliferation was not seen after 14 days in its presence. At a gene expression level, HA did not influence NP cells phenotype after seven days in culture. After seven days in culture, the type I collagen mRNA expression was maintained (p > 0.05). The optimally stabilised and functionalised type II collagen/HA hydrogel system developed in this study shows promise as an injectable reservoir system for intervertebral disc regeneration. PMID: 21276612 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Synergistic effects of the dual release of stromal cell-derived factor-1 and bone morphogenetic protein-2 from hydrogels on bone regeneration. Biomaterials. 2011 Apr;32(11):2797-811 Authors: Ratanavaraporn J, Furuya H, Kohara H, Tabata Y The objective of this study is to evaluate the activity of gelatin hydrogels incorporating combined stromal cell-derived factor-1 (SDF-1) and bone morphogenetic protein-2 (BMP-2) on the in vivo bone regeneration at an ulna critical-sized defect and subcutaneous site of rats, and compared with that of those incorporating either SDF-1 or BMP-2. The similar release profile of SDF-1 and BMP-2 from the hydrogels was observed with or without the combination of BMP-2 and SDF-1, respectively. An enhanced bone regeneration by the hydrogels incorporating combined SDF-1 and BMP-2 was observed. In addition, the implantation of hydrogels incorporating combined SDF-1 and BMP-2 enhanced the expression level of CXC chemokine cell-surface receptor-4 (Cxcr4), Runt-related factor-2 (Runx2), and Osteocalcin genes. The experiments with green fluorescent protein (GFP)-positive Chimeric mice revealed that the recruitment of bone marrow-derived cells was promoted and a vascular-like structure together with strong accumulation of CD31- and CD34-positive cells was observed at the site of hydrogels incorporating combined SDF-1 and BMP-2 implanted. In addition, a large fraction of CD29- and CD44-positive non-hematopoietic cells was detected. It is concluded that the combined release of SDF-1 and BMP-2 enhanced the recruitment of osteogenic cells and angiogenesis, resulting in the synergistic effect on bone regeneration. PMID: 21257197 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Effect of In-Vitro Passaging on the Stem Cell-related Properties of Tendon-Derived Stem Cells (TDSCs) - Implication in Tissue Engineering. Stem Cells Dev. 2011 Jun 1; Authors: Tan Q, Lui PP, Rui YF This study aimed to compare clonogenicity, proliferation, stem cell-related marker expression, senescence, and differentiation potential of rat patellar tendon-derived stem cells (TDSCs) at early (P5), mid (P10) and late (P20, P30) passages. The clonogenicity of the cells was assessed by colony-forming assay while their proliferative potential was assessed by BrdU assay. The surface expression of CD90 and CD73 was assessed by flow cytometry. The cellular senescence was assessed by -galactosidase activity. The adipogenic, chondrogenic and osteogenic differentiation potentials of TDSCs were assessed by standard assays after induction. The mRNA expression of tendon-related markers, Scx and Tnmd, were measured by qRT-PCR. Both the colony numbers and proliferative potential of TDSCs increased with passaging. Concomitantly, there was significant up-regulation of -galactosidase activity with TDSC passaging. The sub-culture of TDSCs downregulated the expression of CD90 and CD73. Lipid droplets were formed in the early and mid passages of TDSCs upon adipogenic induction, but were absent in the late passages. The expression of PPAR2 and C/EBP in TDSCs after adipogenic induction decreased with passaging. Chondrogenesis, proteoglycan deposition, collagen type II protein expression, Col2A1 and Acan mRNA expression were less in pellets formed with later passages of TDSCs after chondrogenic induction. The expression of Scx and Tnmd was lower in the late, compared to early and mid, passages of TDSCs. However, matrix mineralization, Alp and Bglap mRNA expression after osteogenic induction increased with TDSC passaging. Researchers and clinicians should consider the changes of stem cell-related properties of TDSCs when multiplying them in-vitro for tissue engineering. PMID: 21627568 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bladder augmentation using tissue-engineered autologous oral mucosal epithelial cell sheets grafted on demucosalized gastric flaps. Transplantation. 2011 Apr 15;91(7):700-6 Authors: Watanabe E, Yamato M, Shiroyanagi Y, Tanabe K, Okano T At present, autologous intestinal segments are often used for bladder reconstruction. However, the gastrointestinal mucosa often causes various complications. PMID: 21301400 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Three-dimensional honeycomb-patterned chitosan/poly(L-lactic acid) scaffolds with improved mechanical and cell compatibility. J Biomed Mater Res A. 2011 May 31; Authors: Zhao M, Li L, Li X, Zhou C, Li B Micro-size patterned surfaces trigger specific biological responses such as the promotion of cell growth, cell migration, cell differentiation, and ECM production. The aim of this work was to elaborate three-dimensional scaffolds with honeycomb patterned surfaces and large open pores, and to study the influence of surface patterning on cell behavior. In this study, we used water droplets as porogen material to prepare a novel type of chitosan sponge with large open pores on its surface. The sponges obtained were then immersed into 6 wt % Poly(L-lactic acid) chloroform solution to obtain honeycomb patterned composite porous scaffolds. The morphology and mechanical properties were characterized with SEM and compression testing. The fibroblast behaviors in scaffolds were analyzed with SEM, VG, PAS, live-dead staining, and flow cytometer. Results showed that these composite scaffolds possessed better mechanical properties and hierarchical porous structure than pure chitosan sponges. Cell culture revealed that the honeycomb patterned surface had positive influences on fibroblast behaviors, wherein the cell adhesion, proliferation, ECM secretion and viability were improved dramatically. Such a hierarchical composite scaffold would be a suitable candidate for tissue engineering purposes. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2011. PMID: 21630436 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Microscale Technologies and Modular Approaches for Tissue Engineering: Moving toward the Fabrication of Complex Functional Structures. ACS Nano. 2011 May 31; Authors: Gauvin R, Khademhosseini A Micro- and nanoscale technologies have emerged as powerful tools in the fabrication of engineered tissues and organs. Here we focus on the application of these techniques to improve engineered tissue architecture and function using modular and directed self-assembly and highlight the emergence of this new class of materials for biomedical applications. PMID: 21627163 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Differences in valvular and vascular cell responses to strain in osteogenic media. Biomaterials. 2011 Apr;32(11):2885-93 Authors: Ferdous Z, Jo H, Nerem RM Calcification is the primary cause of failure of bioprosthetic and tissue-engineered vascular and valvular grafts. We used tissue-engineered collagen gels containing human aortic smooth muscle cells (HASMC) and human aortic valvular interstitial cells (HAVIC) as a model to investigate cell-mediated differences in early markers of calcification. The HASMCs and HAVICs were isolated from non-sclerotic human tissues. After 21 days of culture in either regular or osteogenic media with or without 10% cyclic strain at 1 Hz, the collagen gels were assessed for DNA content, collagen I, matrix metalloproteinase (MMP)-2 and glycosaminoglycan (GAG) content. The collagen gels containing HASMCs contained significantly greater amounts of collagen I and GAG compared to HAVICs. Although strain increased MMP-2 activity for both cell types, this trend was significant (p ≤ 0.05) only for HAVICs. Cultured gels were also assessed for osteogenic markers calcium content, alkaline phosphatase (ALP), and Runx2 and were present at greater amounts in gels containing HASMCs than HAVICs. Calcium content, Runx2 expression, and ALP activity were also modulated by mechanical strain. The results indicate that cell-mediated differences exist between the vascular and valvular calcification processes. Further investigation is necessary for improved understanding and to detect biomarkers for early detection or prevention of these diseases. PMID: 21284997 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Characterization of a cartilage-like engineered biomass using a self-aggregating suspension culture model: Molecular composition using FT-IRIS. J Orthop Res. 2011 May 31; Authors: Kim M, Kraft JJ, Volk AC, Pugarelli J, Pleshko N, Dodge GR Maintenance of chondrocyte phenotype and robust expression and organization of macromolecular components with suitable cartilaginous properties is an ultimate goal in cartilage tissue engineering. We used a self-aggregating suspension culture (SASC) method to produce an engineered cartilage, "cartilage tissue analog" (CTA). With an objective of understanding the stability of phenotype of the CTA over long periods, we cultured chondrocytes up to 4 years and analyzed the matrix. Both early (eCTAs) (6 months) and aged (aCTAs) (4 years) showed type II collagen throughout with higher concentrations near the edge. Using Fourier transform-infrared imaging spectroscopy (FT-IRIS), proteoglycan/collagen ratio of eCTA was 2.8 times greater than native cartilage at 1 week, but the ratio was balanced to native level (p = 0.017) by 36 weeks. Surprisingly, aCTAs maintained the hyaline characteristics, but there was evidence of calcification within the tissue with a distinct range of intensities. Mineral/matrix ratio of those aCTA with "intensive" calcification was significantly higher (p = 0.017) than the "partial," but when compared to native bone the ratio of "intensive" aCTAs was 2.4 times lower. In this study we utilized the imaging approach of FT-IRIS and have shown that a biomaterial formed is compositionally closely related to natural cartilage for long periods in culture. We show that this culture platform can maintain a CTA for extended periods of time (4 years) and under those conditions signs of mineralization can be found. This method of cartilage tissue engineering is a promising method to generate cartilaginous biomaterial and may have potential to be utilized in both cartilage and boney repairs. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. PMID: 21630329 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Chemical control of FGF-2 release for promoting calvarial healing with adipose stem cells. J Biol Chem. 2011 Apr 1;286(13):11307-13 Authors: Kwan MD, Sellmyer MA, Quarto N, Ho AM, Wandless TJ, Longaker MT Chemical control of protein secretion using a small molecule approach provides a powerful tool to optimize tissue engineering strategies by regulating the spatial and temporal dimensions that are exposed to a specific protein. We placed fibroblast growth factor 2 (FGF-2) under conditional control of a small molecule and demonstrated greater than 50-fold regulation of FGF-2 release as well as tunability, reversibility, and functionality in vitro. We then applied conditional control of FGF-2 secretion to a cell-based, skeletal tissue engineering construct consisting of adipose stem cells (ASCs) on a biomimetic scaffold to promote bone formation in a murine critical-sized calvarial defect model. ASCs are an easily harvested and abundant source of postnatal multipotent cells and have previously been demonstrated to regenerate bone in critical-sized defects. These results suggest that chemically controlled FGF-2 secretion can significantly increase bone formation by ASCs in vivo. This study represents a novel approach toward refining protein delivery for tissue engineering applications. PMID: 21262969 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | The vice chair of the CIRM Legislative Subcommittee, Francisco Prieto, has offered a brief comment on the subject of patent reform, a matter that will come before the panel on Monday.
Prieto, a Sacramento physician, said in an email last night to the California Stem Cell Report,
"I'm not sure we'll take a position, but we do want to be informed, and have a pretty serious interest. The outcome | | | | | | | | | | | | | | | | | | | | | | | | Shades of Tony Podesta. The other shoe is dropping at the $3 billion California stem cell agency.
This time it comes in the form of open-ended approval for the chairman of the agency to hire federal lobbyists. No details are yet available on the CIRM web site. But on June 9, the directors' Finance Committee will convene for 30 minutes to act on the proposal.
All that is known about the | | | | | | | | | | | | | | | | | | | | | | | | The foray by the California stem cell agency into the tricky and arcane world of patent reform triggered a note today from the acting director of the San Diego Consortium for Regenerative Medicine, Xuejun H. Parsons.
She pointed out that the San Diego Regenerative Medicine Institute has a short piece on its web site about the patentability of human embryonic stem cells. CIRM was created by | | | | | | | | | | | | | | | | | | | | | | | | | Acute kidney injury and its management. Contrib Nephrol. 2011;171:218-25 Authors: Chuasuwan A, Kellum JA Acute kidney injury (AKI) is a life-threatening disorder, but one which is potentially reversible. This syndrome is a frequent and serious complication of hospitalized patients. When severe enough to require renal replacement therapy, hospital mortality approaches 60% and recovery among survivors may be as poor as 50%. Moreover, recent evidence using uniform definitions and classifications have revealed that even less severe forms of AKI are associated with reduced survival and other long-term adverse consequences, including progression of chronic kidney disease. Promising new biomarkers are becoming available and new strategies for prevention of AKI in specific situations are being developed. Advanced treatment options, including adsorptive therapy, the renal tubular assist device and stem cell therapy, are also on the horizon. Increasing knowledge in this field is beginning to fill in the missing jigsaw puzzle pieces and a more coherent picture is emerging. Challenges in management of AKI to reduce mortality are sill daunting, however, and more research is urgently needed. The combination of education, risk stratification, prevention, early detection, prompt therapeutic intervention, quality of supportive care, and innovative therapies offer the promise of improving outcomes in patients afflicted with this serious condition. PMID: 21625115 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | The tumor necrosis factor type 2 receptor plays a protective role in tumor necrosis factor-α-induced bone resorption lacunae on mouse calvariae. J Bone Miner Metab. 2011 Jun 1; Authors: Nagano K, Alles N, Mian AH, Shimoda A, Morimoto N, Tamura Y, Shimokawa H, Akiyoshi K, Ohya K, Aoki K Tumor necrosis factor (TNF)-α exerts its biological function via TNF type 1 and type 2 receptors (TNFR1 and TNFR2). We have previously reported that bone resorption induced by lipopolysaccharide (LPS) in TNFR2-deficient mice is accelerated compared to that in wild-type (WT) mice. Although these results suggested that TNFR2 might have a protective role in bone resorption, we could not exclude the possibility that TNFR2 has no role in bone resorption. To clarify the role of TNFR2, we developed a TNF-α-induced bone resorption model using cholesterol-bearing pullulan nanogel as a TNF-α carrier to minimize the influence of inflammatory cytokines other than TNF-α. Injections of human TNF-α (hTNF), an agonist of mouse TNFR1, stimulated bone resorption lacunae on the calvariae in WT mice, but mouse TNF-α (mTNF), an agonist of both mouse TNFR1 and TNFR2, could not. To eliminate the possibility that the TNFR1 agonistic effects of hTNF were stronger than those of mTNF, we used the same model in TNFR2-deficient mice. Injection of mTNF resulted in clear bone resorption lacunae to the same extent observed after using hTNF in the TNFR2-deficient mice. Histomorphometric analysis of osteoclast number supported the observed changes in bone resorption lacunae. These data suggest that TNFR2 has a protective role in TNF-α-induced bone resorption. PMID: 21626455 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A multiscale mechanobiological modelling framework using agent-based models and finite element analysis: application to vascular tissue engineering. Biomech Model Mechanobiol. 2011 May 31; Authors: Zahedmanesh H, Lally C Computational models of mechanobiological systems have been widely used to provide insight into these systems and also to predict their behaviour. In this context, vascular tissue engineering benefits from further attention given the challenges involved in developing functional low calibre vascular grafts with long-term patency. In this study, a novel multiscale mechanobiological modelling framework is presented, which takes advantage of lattice-free agent-based models coupled with the finite element method to investigate the dynamics of VSMC growth in vascular tissue engineering scaffolds. The results illustrate the ability of the mechanobiological modelling approach to capture complex multiscale mechanobiological phenomena. Specifically, the framework enabled the study of the influence of scaffold compliance and loading regime in regulating the growth of VSMCs in vascular scaffolds and their role in development of intimal hyperplasia (IH). The model demonstrates that low scaffold compliance compared to host arteries leads to increased luminal ingrowth and IH development. In addition, culture of a tissue-engineered blood vessel under a pulsatile luminal pressure reduced luminal ingrowth and enhanced collagen synthesis within the scaffold compared to non-pulsatile culture. The mechanobiological framework presented provides a robust platform for testing hypotheses in vascular tissue engineering and lends itself to use as an optimisation design tool. PMID: 21626394 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Modulation of immunological properties of allogeneic mesenchymal stem cells by collagen scaffolds in cartilage tissue engineering. J Biomed Mater Res A. 2011 May 27; Authors: Yuan T, Li K, Guo L, Fan H, Zhang X Influence of the structures of some collagen scaffolds on immunological properties of the seeded allogeneic mesenchymal stem cells (MSCs) was studied in this article. Hydrogels, sponge, and membrane were prepared from type-I collagen. These scaffolds were seeded with neonatal rabbit MSCs and cultured for different periods. Changes of the immunological properties associated with different scaffolds were analyzed and compared. It was found that the expression of major histocompatibility complex (MHC) class I and II molecules on MSCs increased gradually in all scaffolds, but the least increment was recorded in hydrogels. Mixed lymphocyte reactions (MLR) showed that the MSC-hydrogel constructs invoked considerably low allogeneic lymphocytes proliferation. Even in presence of interferon-γ (IFN-γ), the hydrogels with higher concentration gave comparatively lower increment of MHC-II expression and allogeneic lymphocytes proliferation. These results suggest that different scaffold structures may provide different microenvironments and extents of isolation from the host immune system for the seed cells, thereby affecting their immunological properties. Therefore, scaffold structures may modulate the immunological properties of tissue-engineered cartilage with allogeneic cells. Hydrogels, especially which were prepared from higher collagen concentrations, were found to be a promising scaffold structure, from the perspective of avoiding severe immune rejection. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011. PMID: 21626664 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The potential of amniotic fluid stem cells for cellular therapy and tissue engineering. Expert Opin Biol Ther. 2011 May 31; Authors: Klemmt PA, Vafaizadeh V, Groner B Introduction: Foetal cells present in amniotic fluid (AF) have been used for many years to perform prenatal genetic screening. Recent reports suggested that these cells might have additional benefits. AF contains, in addition to committed and differentiated cells, a subpopulation with stem cell characteristics. AF-derived stem cells (AFS) have functions found in mesenchymal stem cells, but in addition, exhibit a potent expansion capacity and plasticity. AFS are able to undergo multi-lineage differentiation and produce progeny indicative of all three germ layers. Areas covered: The experimental approaches available to isolate AFS and their potential for tissue engineering, the repair of organs through cell replacement and tissue regeneration. Expert opinion: The deployment of AFS for tissue regeneration offers advantages over the use of embryonic or adult stem cells: i) AF represents a convenient and non-contested source for obtaining stem cells; ii) their derivation is relatively simple and rapid; iii) no feeder layers are required for their cultivation; iv) they display no spontaneous differentiation in culture; and v) their stem cell phenotype is not affected by long-term storage. The application of AFS for tissue replacement therapies in vivo is at a very early stage, but existing studies indicate great potential for clinical use. PMID: 21623704 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A Novel Insight to the Functional Role of Stathmin 1 in IgE-Mediated Activation of RBL-2H3 Cells. Iran J Allergy Asthma Immunol. 2011 Jun;10(2):73-80 Authors: Sadroddiny E, J G Moir A, A Helm B IgE-mediated cell signaling, induced by cross-linking of high affinity receptor for IgE (FcεRI) in the presence of antigen (Ag), is a well known mechanism described for mast cell activation in allergy and hypersensitivity reactions, which induces a spectrum of cellular responses such as secretion and up-regulation of cell surface FcεRI. Although for several years IgE binding to FcεRI was considered to be a passive sensitization process, the outcomes of several recent studies have revealed a variety of different cellular responses to IgE binding compared to IgE plus Antigen binding. The present study applied a functional proteomics-based approach to investigate mast cell signaling events and provided new insights to FcεRI-mediated cell signaling in RBL-2H3.1 cells, and may point to the activation of alternative signaling pathways in response to IgE or IgE plus Ag. Comparative analysis by 2-D PAGE of RBL cells activated with IgE plus Ag for three and four hours compared to non-activated cells was followed by mass spectrometric protein identification and provided evidence for the induction of Stathmin 1 (STMN1) gene expression in response to IgE plus Ag activation.Complementary SDS-PAGE analysis showed a distinct up-regulation of STMN1 induction in response to challenge with IgE plus Ag compared to sensitization with IgE only. Phosphoproteomics analysis gave evidence for significant increase at phosphorylation of STMN1 on ser16 after 1min, though a slight rise at 5 min, and on ser38 after 1 and 5min sensitization with IgE and a similar result was observed for 1min IgE plus Ag-activation. IgE plus Ag-activation was also found to induce the phosphorylation of ser38 to a greater extent than sensitization with IgE. In contrast, IgE alone was more effective than IgE plus Ag at inducing phosphorylation of ser16. Collectively this study provides further insights into the role of stathmin 1 in FcRI-mediated activation of cells of mast cell lineage and might shed light on the diverse response of these cells to IgE or IgE plus Ag. PMID: 21625015 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Biomechanical study on decellularized laryngeal scaffold in dogs.] Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2011 Apr;46(4):331-335 Authors: Xu L, Cui PC, Chen ZF, Ma RN OBJECTIVE: To evaluate the biomechanical characteristics of the decellularized laryngeal scaffold. METHODS: Ten Chinese adult dogs were randomly divided into two groups: perfusion group (n = 5) and control group (n = 5). The acellular larynx scaffold was obtained from dogs through cranial thyroid arteries perfusion with detergents. Comparative examinations were performed by the macroscopic view, histological view (hematoxylin and eosin stain, Alcian blue stain and Masson stain), scanning electron microscope (SEM) and biomechanical properties between perfusion group and control group. RESULTS: Macroscopic view showed that the decellularized laryngeal scaffold appeared pale asphyxia. HE stain indicated that there were little acellular traces of muscle and mucosa. Alcian blue stain, Masson stain and scanning electron microscope (SEM) suggested that there were no obvious changes about lycosaminoglycan and collagen. The compressive modulus of thyroid cartilage was (1.06 ± 0.07) MPa (x(-) ± s) in experimental groups and (1.15 ± 0.11) MPa in control group, showing no significant difference (t = 1.424, P > 0.05), neither in compressive modulus of annular cartilage (1.68 ± 0.11) MPa in experimental groups and (1.67 ± 0.09) MPa in control group (t = 0.185, P > 0.05). The tensile strength of thyroid cartilage between experimental (5.74 ± 0.88) MPa and control groups (6.18 ± 1.33) MPa did not have the statistical significance (t = 0.627, P > 0.05). CONCLUSION: These results indicate that perfusion method can construct a perfect biomechanical acellular larynx scaffold which could be a better selection for laryngeal reconstruction with tissue engineering method. PMID: 21624255 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Compositional control of poly(ethylene glycol) hydrogel modulus independent of mesh size. J Biomed Mater Res A. 2011 May 27; Authors: Browning MB, Wilems T, Hahn M, Cosgriff-Hernandez E Poly(ethylene glycol) (PEG) hydrogels are of great interest in tissue engineering because of their established biocompatibility, high permeability, and tunable material properties. However, rational design of PEG hydrogel scaffold properties has been inhibited by the interdependence of key material properties such as modulus and mesh size. This study examined the effect of an acrylated 4-arm PEG cross-linker on gel modulus and mesh size as a means of inducing local increases in cross-link density to decouple these two parameters. It was determined that adding the 4-arm PEG cross-linker to PEG hydrogels resulted in statistically significant increases in both tensile and compressive modulus while having minimal effects on overall gel mesh size. The incorporation of the 4-arm PEG cross-linker also broadened the range of achievable mechanical properties. This study provides the methodology to independently tune PEG hydrogel modulus and mesh size, which may be utilized in future investigations of the individual and combined effects of PEG hydrogel modulus and mesh size on cell behavior and viability. It also presents a more finely tunable hydrogel scaffold with utility in a broad range of tissue engineering applications. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011. PMID: 21626658 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Tendon tissue engineering: Progress, challenges, and translation to the clinic. J Musculoskelet Neuronal Interact. 2011 Jun;11(2):163-73 Authors: Shearn JT, Kinneberg KR, Dyment NA, Galloway MT, Kenter K, Wylie C, Butler DL The tissue engineering field has made great strides in understanding how different aspects of tissue engineered constructs (TECs) and the culture process affect final tendon repair. However, there remain significant challenges in developing strategies that will lead to a clinically effective and commercially successful product. In an effort to increase repair quality, a better understanding of normal development, and how it differs from adult tendon healing, may provide strategies to improve tissue engineering. As tendon tissue engineering continues to improve, the field needs to employ more clinically relevant models of tendon injury such as degenerative tendons. We need to translate successes to larger animal models to begin exploring the clinical implications of our treatments. By advancing the models used to validate our TECs, we can help convince our toughest customer, the surgeon, that our products will be clinically efficacious. As we address these challenges in musculoskeletal tissue engineering, the field still needs to address the commercialization of products developed in the laboratory. TEC commercialization faces numerous challenges because each injury and patient is unique. This review aims to provide tissue engineers with a summary of important issues related to engineering tendon repairs and potential strategies for producing clinically successful products. PMID: 21625053 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Melt-derived bioactive glass scaffolds produced by a gel-cast foaming technique. Acta Biomater. 2011 Apr;7(4):1807-16 Authors: Wu ZY, Hill RG, Yue S, Nightingale D, Lee PD, Jones JR Porous melt-derived bioactive glass scaffolds with interconnected pore networks suitable for bone regeneration were produced without the glass crystallizing. ICIE 16 (49.46% SiO(2), 36.27% CaO, 6.6% Na(2)O, 1.07% P(2)O(5) and 6.6% K(2)O, in mol.%) was used as it is a composition designed not to crystallize during sintering. Glass powder was made into porous scaffolds by using the gel-cast foaming technique. All variables in the process were investigated systematically to devise an optimal process. Interconnect size was quantified using mercury porosimetry and X-ray microtomography (μCT). The reagents, their relative quantities and thermal processing protocols were all critical to obtain a successful scaffold. Particularly important were particle size (a modal size of 8 μm was optimal); water and catalyst content; initiator vitality and content; as well as the thermal processing protocol. Once an optimal process was chosen, the scaffolds were tested in simulated body fluid (SBF) solution. Amorphous calcium phosphate formed in 8h and crystallized hydroxycarbonate apatite (HCA) formed in 3 days. The compressive strength was approximately 2 MPa for a mean interconnect size of 140 μm between the pores with a mean diameter of 379 μm, which is thought to be a suitable porous network for vascularized bone regeneration. This material has the potential to bond to bone more rapidly and stimulate more bone growth than current porous artificial bone grafts. PMID: 21130188 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Comparison of bacterial adhesion and cellular proliferation on newly developed three-dimensional scaffolds manufactured by rapid prototyping technology. J Biomed Mater Res A. 2011 May 27; Authors: Al-Ahmad A, Schubert C, Carvalho C, Thoman Y, Wittmer A, Metzger M, Hellwig E, Swieszkowski W, Wiedmann-Al-Ahmad M Scaffolds used in the field of tissue engineering should facilitate the adherence, spreading, and ingrowth of cells as well as prevent microbial adherence. For the first time, this study simultaneously deals with microbial and tissue cell adhesion to rapid prototyping-produced 3D-scaffolds. The cell growth of human osteosarcoma cells (CAL-72) over a time period of 3-11 days were examined on three scaffolds (PLGA, PLLA, PLLA-TCP) and compared to the adhesion of salivary microorganisms and representative germs of the oral flora (Porphyromonas gingivalis, Prevotella nigrescens, Candida albicans, Enterococcus faecalis, Streptococcus mutans, and Streptococcus sanguinis). Scanning electron microscopy (SEM), cell proliferation measurements, and determination of the colony forming units (CFU) were performed. The cell proliferation rates on PLLA and PLLA-TCP after 3, 7, and 11 days of cultivation were higher than on PLGA. On day 3 the proliferation rates on PLLA and PLLA-TCP, and on day 5 on PLLA-TCP, proved to be significantly higher compared to that of the control (culture plate). The strain which showed the most CFUs on all of the investigated scaffolds was P. gingivalis, followed by E. faecalis. No significant CFU differences were determined examining P. gingivalis among the biomaterials. In contrast, E. faecalis was significantly more adherent to PLGA and PLLA compared to PLLA-TCP. The lowest CFU values were seen with C. albicans and P. nigrescens. Salivary born aerobic and anaerobic microorganisms adhered significantly more to PLGA compared to PLLA-TCP. These results supported by SEM point out the high potential of PLLA-TCP in the field of tissue engineering. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011. PMID: 21626662 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Expanded polytetrafluoroethylene as a substrate for retinal pigment epithelial cell growth and transplantation in age-related macular degeneration. Br J Ophthalmol. 2011 Apr;95(4):569-73 Authors: Krishna Y, Sheridan C, Kent D, Kearns V, Grierson I, Williams R Retinal pigment epithelial (RPE) transplantation presents a potential treatment for age-related macular degeneration (AMD). A suitable transplant membrane that can support an intact functioning RPE monolayer is required. Expanded polytetrafluoroethylene (ePTFE) possesses the physical properties required for a transplanting device; however, cells do not attach and spread on ePTFE. This study investigated the ability of surface-modified ePTFE to optimise the growth and function of healthy RPE monolayers. PMID: 21317216 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Endogenous tissue engineering: PTH therapy for skeletal repair. Cell Tissue Res. 2011 May 31; Authors: Takahata M, Awad HA, O'Keefe RJ, Bukata SV, Schwarz EM Based on its proven anabolic effects on bone in osteoporosis patients, recombinant parathyroid hormone (PTH(1-34)) has been evaluated as a potential therapy for skeletal repair. In animals, the effect of PTH(1-34) has been investigated in various skeletal repair models such as fractures, allografting, spinal arthrodesis and distraction osteogenesis. These studies have demonstrated that intermittent PTH(1-34) treatment enhances and accelerates the skeletal repair process via a number of mechanisms, which include effects on mesenchymal stem cells, angiogenesis, chondrogenesis, bone formation and resorption. Furthermore, PTH(1-34) has been shown to enhance bone repair in challenged animal models of aging, inflammatory arthritis and glucocorticoid-induced bone loss. This pre-clinical success has led to off-label clinical use and a number of case reports documenting PTH(1-34) treatment of delayed-unions and non-unions have been published. Although a recently completed phase 2 clinical trial of PTH(1-34) treatment of patients with radius fracture has failed to achieve its primary outcome, largely because of effective healing in the placebo group, several secondary outcomes are statistically significant, highlighting important issues concerning the appropriate patient population for PTH(1-34) therapy in skeletal repair. Here, we review our current knowledge of the effects of PTH(1-34) therapy for bone healing, enumerate several critical unresolved issues (e.g., appropriate dosing regimen and indications) and discuss the long-term potential of this drug as an adjuvant for endogenous tissue engineering. PMID: 21626290 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Pulp tissue from primary teeth: new source of stem cells. J Appl Oral Sci. 2011 Jun;19(3):189-94 Authors: Telles PD, Machado MA, Sakai VT, Nör JE SHED (stem cells from human exfoliated deciduous teeth) represent a population of postnatal stem cells capable of extensive proliferation and multipotential differentiation. Primary teeth may be an ideal source of postnatal stem cells to regenerate tooth structures and bone, and possibly to treat neural tissue injury or degenerative diseases. SHED are highly proliferative cells derived from an accessible tissue source, and therefore hold potential for providing enough cells for clinical applications. In this review, we describe the current knowledge about dental pulp stem cells and discuss tissue engineering approaches that use SHED to replace irreversibly inflamed or necrotic pulps with a healthy and functionally competent tissue that is capable of forming new dentin. PMID: 21625731 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Toward a strategic plan for pulp healing: from repair to regeneration. Clin Oral Investig. 2011 Feb;15(1):1-2 Authors: Goldberg M, Schmalz G PMID: 21234623 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | [Cardiac stem cells]. Kardiol Pol. 2010 Oct;68(10):1163-7 Authors: Jadczyk T, Wojakowski W PMID: 20967718 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Assessment of growth factor treatment on fibrochondrocyte and chondrocyte co-cultures for TMJ fibrocartilage engineering. Acta Biomater. 2011 Apr;7(4):1710-8 Authors: Kalpakci KN, Kim EJ, Athanasiou KA Treatments for patients suffering from severe temporomandibular joint (TMJ) dysfunction are limited, motivating the development of strategies for tissue regeneration. In this study, co-cultures of fibrochondrocytes (FCs) and articular chondrocytes (ACs) were seeded in agarose wells, and supplemented with growth factors, to engineer tissue with biomechanical properties and extracellular matrix composition similar to native TMJ fibrocartilage. In the first phase, growth factors were applied alone and in combination, in the presence or absence of serum, while in the second phase, the best overall treatment was applied at intermittent dosing. Continuous treatment of AC/FC co-cultures with TGF-β1 in serum-free medium resulted in constructs with glycosaminoglycan/wet weight ratios (12.2%), instantaneous compressive moduli (790 kPa), relaxed compressive moduli (120 kPa) and Young's moduli (1.87 MPa) that overlap with native TMJ disc values. Among co-culture groups, TGF-β1 treatment increased collagen deposition ∼20%, compressive stiffness ∼130% and Young's modulus ∼170% relative to controls without growth factor. Serum supplementation, though generally detrimental to functional properties, was identified as a powerful mediator of FC construct morphology. Finally, both intermittent and continuous TGF-β1 treatment showed positive effects, though continuous treatment resulted in greater enhancement of construct functional properties. This work proposes a strategy for regeneration of TMJ fibrocartilage and its future application will be realized through translation of these findings to clinically viable cell sources. PMID: 21185408 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex. Br J Dermatol. 2011 May 28; Authors: García M, Santiago JL, Terrón A, Hernández-Martín A, Vicente A, Fortuny C, De Lucas R, López JC, Cuadrado-Corrales N, Holguín A, Illera N, Duarte B, Sánchez-Jimeno C, Llames S, García E, Ayuso C, Martínez-Santamaría L, Castiglia D, De Luca N, Torrelo A, Mechan D, Baty D, Zambruno G, Escámez MJ, Del Río M Background: Basal epidermolysis bullosa simplex (EBS) is a group of blistering genodermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14. Recessive mutations represent about 5% of all EBS mutations, being common and specific in populations with high consanguinity, where affected patients show severe phenotypes. Objective: Accomplish the first mutational analysis in EBS patients of Spanish origin and delineate a comprehensive genotype-phenotype correlation. Patients/Methods: 21 EBS families were analyzed. Immunofluorescence mapping at dermo-epidermal junction level was performed on patient skin biopsies. Mutation screening of the entire coding sequences of KRT5 and KRT14 in genomic DNA was assessed by PCR and direct sequencing. Results: KRT5 or KRT14 causative mutations were identified in 18 of the 21 EBS families. 14 different mutations were disclosed, of which 12 were dominant missense mutations and two truncating recessive mutations. Five of the 14 mutations were novel including three dominant in KRT5 (p.V186E, p.T321P and p.A428T) and two recessive in KRT14 (p.K116X and p.K250RfsX8). The two EBS patients carrying homozygous recessive mutations were affected by severe phenotypes and belong to consanguineous families. All 5 families with EBS Dowling-Meara subtype (EBS-DM), carried recurrent mutations affecting the highly conserved ends of the alpha-helical rod domain of K5 and K14. The seven mutations associated to localized EBS subtype (EBS-loc) were widely distributed along KRT5 and KRT14 genes. Two families with mottled pigmentation (EBS-MP) carried the P25L mutation in KRT5, commonly associated with this subtype. Conclusions: This study further confirms the genotype-phenotype correlation established for EBS in other ethnic groups, being the first in a Mediterranean country (excluding Israel). This study adds two novel recessive mutations to the world record so far including a total of 14 mutations. As in previous reports, recessive mutations resulted in lack of keratin K14, giving rise to a generalized and severe presentation. PMID: 21623745 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effect of Boron on Osteogenic Differentiation of Human Bone Marrow Stromal Cells. Biol Trace Elem Res. 2011 May 31; Authors: Ying X, Cheng S, Wang W, Lin Z, Chen Q, Zhang W, Kou D, Shen Y, Cheng X, Rompis FA, Peng L, Zhu Lu C Bone marrow stromal cells (BMSCs) have been well established as an ideal source of cell-based therapy for bone tissue engineering applications. Boron (B) is a notable trace element in humans; so far, the effects of boron on the osteogenic differentiation of BMSCs have not been reported. The aim of this study was to evaluate the effects of boron (0, 1, 10,100, and 1,000 ng/ml) on osteogenic differentiation of human BMSCs. In this study, BMSCs proliferation was analyzed by cell counting kit-8 (CCK8) assay, and cell osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, Von Kossa staining, and real-time PCR. The results indicated that the proliferation of BMSCs was no different from the control group when added with B at the concentration of 1, 10, and 100 ng/ml respectively (P > 0.05); in contrast, 1,000 ng/ml B inhibited the proliferation of BMSCs at days 4, 7, and 14 (P < 0.05). By ALP staining, we discovered that BMSCs treated with 10 and 100 ng/ml B presented a higher ALP activity compared with control (P < 0.05). By real-time PCR, we detected the messenger RNA expression of ALP, osteocalcin, collagen type I, and bone morphogenetic proteins 7 were also increased in 10 and 100 ng/ml B treatment groups (P < 0.05). The calcium depositions were increased in 1 and 10 ng/ml B treatment groups (P < 0.05). Taken all together, it was the first time to report that B could increase osteogenic effect by stimulating osteogenic differentiation-related marker gene synthesis during the proliferation and differentiation phase in human BMSCs and could be a promising approach for enhancing osteogenic capacity of cell-based construction in bone tissue engineering. PMID: 21625915 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Fibrillar films obtained from sodium soap fibers and polyelectrolyte multilayers. J Biomed Mater Res A. 2011 May 27; Authors: Zawko SA, Schmidt CE An objective of tissue engineering is to create synthetic polymer scaffolds with a fibrillar microstructure similar to the extracellular matrix. Here, we present a novel method for creating polymer fibers using the layer-by-layer method and sacrificial templates composed of sodium soap fibers. Soap fibers were prepared from neutralized fatty acids using a sodium chloride crystal dissolution method. Polyelectrolyte multilayers (PEMs) of polystyrene sulfonate and polyallylamine hydrochloride were deposited onto the soap fibers, crosslinked with glutaraldehyde, and then the soap fibers were leached with warm water and ethanol. The morphology of the resulting PEM structures was a dense network of fibers surrounded by a nonfibrillar matrix. Microscopy revealed that the PEM fibers were solid structures, presumably composed of polyelectrolytes complexed with residual fatty acids. These fibrillar PEM films were found to support the attachment of human dermal fibroblasts. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011. PMID: 21626660 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A novel strontium-doped calcium polyphosphate/erythromycin/poly(vinyl alcohol) composite for bone tissue engineering. J Biomed Mater Res A. 2011 May 27; Authors: Song W, Ren W, Wan C, Esquivel AO, Shi T, Blasier R, Markel DC It is our goal to develop bactericidal bone scaffolds with osteointegration potential. In this study, poly(vinyl alcohol) (PVA) coating (7%) was applied to an erythromycin (EM)-impregnated strontium-doped calcium polyphosphate (SCPP) scaffold using a simple slurry dipping method. MicroCT analysis showed that PVA coating reduced the average pore size and the percentage of pore interconnectivity to some extent. Compressive strength tests confirmed that the PVA coating significantly increased material elasticity and slightly enhanced the scaffold mechanical strength. It was also confirmed that the PVA coatings allowed a sustained EM release that is controlled by diffusion through the intact PVA hydrogel layer, irrespective of the drug solubility. PVA coating did not inhibit the EM bioactivity when the scaffolds were immersed in simulated body fluid for up to 4 weeks. EM released from SCPP-EM-PVA composite scaffolds maintained its capability of bacterial growth (S. aureus) inhibition. PVA coating is biocompatible and nontoxic to MC3T3 preosteoblast cells. Furthermore, we found that SCPP-EM-PVA composite scaffolds and their eluants remarkably inhibited RANKL-induced osteoclastogenesis in a murine RAW 264.7 macrophage cell line. Thus, this unique multifunctional bioactive composite scaffold has the potential to provide controlled delivery of relevant drugs for bone tissue engineering. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011. PMID: 21626667 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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