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| Association of polymorphisms of zinc metalloproteinases with clinical response to stem cell therapy.
July 14, 2010 at 6:23 AM
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| | Association of polymorphisms of zinc metalloproteinases with clinical response to stem cell therapy. Herz. 2010 Jul 14; Authors: Panovsky R, Vasku A, Meluzin J, Kaminek M, Mayer J, Janousek S, Kincl V, Groch L, Navratil M AIM: The purpose of this study was to assess the associations of polymorphisms in two metalloproteinase genes-metalloproteinase-2 (MMP-2) and angiotensin converting enzyme (ACE)-with clinical response to autologous transplantation of mononuclear bone marrow cells (MBMC) in patients with acute myocardial infarction. METHODS: The double centre study included 48 patients with a first acute myocardial infarction treated with primary coronary angioplasty, stent implantation and transplantation of MBMC. According to the changes in perfusion defect size, left ventricle ejection fraction, end-systolic volume and peak systolic velocity of the infracted wall (dSaMI) after cell therapy, the patients were retrospectively divided into group A (responders) and group B (non-responders). Genomic DNA was isolated from peripheral leukocytes by a standard technique using proteinase K. Three MMP-2 promoter (-1575G/A, -1306C/T and -790T/G) as well as I/D ACE gene polymorphisms were detected by PCR methods with restriction analyses (when necessary) according to standard protocols. RESULTS: Of the 48 patients who received MBMC transplantation, 17 responded to the therapy. There were no significant differences in the prevalence of matrix metalloproteinase-2 triple genotype GGCCTT between responder/non-responder groups (71% versus 61%, p=0.375). Similarly, no differences in either genotype distribution or allelic frequencies of I/D ACE polymorphism between responders and non-responders to the cell therapy were observed (p=0.933). Compared to patients with ACE genotype ID or DD, the patients with ACE II genotype significantly improved in regional systolic LV function of the infarcted wall after implantations of MBMC (dSaMI - 0.4 versus 1.4 cm/s, p=0.037). CONCLUSION: In our study, the ACE genotype II was associated with improvement of regional systolic LV function of the infarcted wall after implantations of MBMC. The detected polymorphism in matrix metalloproteinase-2 gene was not associated with clinical response to cell therapy. PMID: 20625691 [PubMed - as supplied by publisher] | | |
| [Surgical intramyocardial stem cell therapy for chronic ischemic heart failure.]
July 14, 2010 at 6:23 AM
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| | [Surgical intramyocardial stem cell therapy for chronic ischemic heart failure.] Herz. 2010 Jul 14; Authors: Kaminski A, Donndorf P, Klopsch C, Steinhoff G Chronic ischemic heart disease patients are already being treated worldwide with bone marrow stem cells both in the context of clinical studies and in therapy trials. By combining this therapy with established revascularization procedures such as bypass surgery, a high level of patient safety can be achieved. To date, no stem cell-related cardiac complications following intramyocardial injection of bone marrow-derived stem cells during CABG (coronary artery bypass graft) surgery have been reported. The functional advantage conferred by surgical bone marrow stem cell therapy is a 7.2% increase in LVEF (left ventricular ejection fraction) compared to controls. Randomized placebo-controlled trials, like the German trial PERFECT, are needed to obtain a more evidence-based assessment of this therapy. PMID: 20625690 [PubMed - as supplied by publisher] | | |
| CD34+ cell mobilization and upregulation of myocardial cytokines in a rabbit model of myocardial ischemia.
July 14, 2010 at 6:23 AM
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| | CD34+ cell mobilization and upregulation of myocardial cytokines in a rabbit model of myocardial ischemia. Int J Cardiol. 2010 Jul 10; Authors: Zhao Q, Sun C, Xu X, Zhou J, Wu Y, Tian Y, Yuan Z, Liu Z BACKGROUND: Studies have suggested that myocardial infarction may induce bone marrow stem cell mobilization and homing to the infarcted area, contributing to myocardial repair and tissue regeneration. Despite some encouraging results using stem cell therapy for myocardial regeneration in humans and animals, the mechanisms behind this activity remain unclear. In this study, we investigate stem cell mobilization and homing in ischemic myocardium, and investigate the involvement of cytokines TNFalpha and VEGF in this process. METHODS AND RESULTS: Myocardial ischemia models were created by partial ligation of the left anterior descending coronary artery in Japanese white male rabbits. Immunohistochemistry analysis of ischemic myocardium showed the presence of VEGF and TNFalpha along with homing of CD34 positive (CD34+) cells to the region in the 7days following surgery. During the same period, an increase in percentage of CD34+ cells in peripheral blood and in VEGF and TNFalpha mRNA expression in ischemic tissue was observed in animals that underwent partial LAD ligation. Terminal dUTP nick end-labeling (TUNEL) showed that cell apoptosis in the ischemic myocardium decreased between days 7 and 28 following surgery. None of these changes were observed in animals that underwent sham operation. CONCLUSIONS: In the early stages of myocardial ischemia, bone marrow stem cells are mobilized and home to ischemic myocardium with a concomitant increase in expression of cytokines VEGF and TNFalpha. Furthermore, cell apoptosis occurs in the ischemic myocardium, possibly due to the activity of TNFalpha which is thought to induce cardiomyocyte apoptosis. PMID: 20624659 [PubMed - as supplied by publisher] | | |
| Stem cell therapies to treat muscular dystrophy: progress to date.
July 14, 2010 at 6:23 AM
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| | Stem cell therapies to treat muscular dystrophy: progress to date. BioDrugs. 2010 Aug 1;24(4):237-47 Authors: Meregalli M, Farini A, Parolini D, Maciotta S, Torrente Y Muscular dystrophies are heritable, heterogeneous neuromuscular disorders and include Duchenne and Becker muscular dystrophies (DMD and BMD, respectively). DMD patients exhibit progressive muscle weakness and atrophy followed by exhaustion of muscular regenerative capacity, fibrosis, and eventually disruption of the muscle tissue architecture. In-frame mutations in the dystrophin gene lead to expression of a partially functional protein, resulting in the milder BMD. No effective therapies are available at present. Cell-based therapies have been attempted in an effort to promote muscle regeneration, with the hope that the host cells would repopulate the muscle and improve muscle function and pathology. Injection of adult myoblasts has led to the development of new muscle fibers, but several limitations have been identified, such as poor cell survival and limited migratory ability. As an alternative to myoblasts, stem cells were considered preferable for therapeutic applications because of their capacity for self-renewal and differentiation potential. In recent years, encouraging results have been obtained with adult stem cells to treat human diseases such as leukemia, Parkinson's disease, stroke, and muscular dystrophies. Embryonic stem cells (ESCs) can be derived from mammalian embryos in the blastocyst stage, and because they can differentiate into a wide range of specialized cells, they hold potential for use in treating almost all human diseases. Several ongoing studies focus on this possibility, evaluating differentiation of specific cell lines from human ESCs (hESCs) as well as the potential tumorigenicity of hESCs. The most important limitation with using hESCs is that it requires destruction of human blastocysts or embryos. Conversely, adult stem cells have been identified in various tissues, where they serve to maintain, generate, and replace terminally differentiated cells within their specific tissue as the need arises for cell turnover or from tissue injury. Moreover, these cells can participate in regeneration of more than just their specific tissue type. Here we describe multiple types of muscle- and fetal-derived myogenic stem cells, their characterization, and their possible use in treating muscular dystrophies such as DMD and BMD. We also emphasize that the most promising possibility for the management and therapy of DMD and BMD is a combination of different approaches, such as gene and stem cell therapy. PMID: 20623990 [PubMed - in process] | | |
| Adipose tissue-derived progenitors for engineering osteogenic and vasculogenic grafts.
July 14, 2010 at 6:21 AM
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| | Adipose tissue-derived progenitors for engineering osteogenic and vasculogenic grafts. J Cell Physiol. 2010 Jul 12; Authors: Scherberich A, Müller AM, Schäfer DJ, Banfi A, Martin I The current need for bone grafts in orthopedic and reconstructive surgery cannot be satisfied by autologous tissue transplant due to its limited availability and significant associated morbidity. Tissue engineering approaches could supply sufficient amounts of bone substitutes by exploiting the ability to harvest autologous osteogenic progenitors associated with suitable porous materials. However, the generation of clinically relevant-sized constructs is critically hampered by limited vascularization, with consequent engraftment and survival only of a thin outer shell, upon in vivo implantation. To overcome this limitation, different non-mutually exclusive approaches have recently been developed to promote or accelerate graft vascularization, from angiogenic growth factor gene delivery to surgical pre-vascularisation of the construct before implantation. A simple, promising strategy involves the co-culture of vasculogenic cells to form an intrinsic vascular network inside the graft in vitro, which can rapidly anastomose with the host blood vessels in vivo. Recent data have shown that adipose tissue-derived stromal vascular fraction (SVF) may provide an efficient, convenient and autologous source for both osteogenic and endothelial cells. When SVF progenitors were cultured in appropriate bioreactor systems and ectopically implanted, a functional vascular network connected to the host was formed concomitantly to bone formation. Future studies should aim at demonstrating that this approach effectively supports survival of scaled up cell-based bone grafts at an orthotopic site. The procedure should also be adapted to become compatible with an intra-operative timeline and complemented with the definition of suitable potency markers, to facilitate its development into a simplified, reproducible and cost-effective clinical treatment. J. Cell. Physiol. (c) 2010 Wiley-Liss, Inc. PMID: 20626000 [PubMed - as supplied by publisher] | | |
| 2010 Nicolas Andry Award: Multipotent Adult Stem Cells from Adipose Tissue for Musculoskeletal Tissue Engineering.
July 14, 2010 at 6:21 AM
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| | 2010 Nicolas Andry Award: Multipotent Adult Stem Cells from Adipose Tissue for Musculoskeletal Tissue Engineering. Clin Orthop Relat Res. 2010 Jul 13; Authors: Guilak F, Estes BT, Diekman BO, Moutos FT, Gimble JM BACKGROUND: Cell-based therapies such as tissue engineering provide promising therapeutic possibilities to enhance the repair or regeneration of damaged or diseased tissues but are dependent on the availability and controlled manipulation of appropriate cell sources. QUESTIONS/PURPOSES: The goal of this study was to test the hypothesis that adult subcutaneous fat contains stem cells with multilineage potential and to determine the influence of specific soluble mediators and biomaterial scaffolds on their differentiation into musculoskeletal phenotypes. METHODS: We reviewed recent studies showing the stem-like characteristics and multipotency of adipose-derived stem cells (ASCs), and their potential application in cell-based therapies in orthopaedics. RESULTS: Under controlled conditions, ASCs show phenotypic characteristics of various cell types, including chondrocytes, osteoblasts, adipocytes, neuronal cells, or muscle cells. In particular, the chondrogenic differentiation of ASCs can be induced by low oxygen tension, growth factors such as bone morphogenetic protein-6 (BMP-6), or biomaterial scaffolds consisting of native tissue matrices derived from cartilage. Finally, focus is given to the development of a functional biomaterial scaffold that can provide ASC-based constructs with mechanical properties similar to native cartilage. CONCLUSIONS: Adipose tissue contains an abundant source of multipotent progenitor cells. These cells show cell surface marker profiles and differentiation characteristics that are similar to but distinct from other adult stem cells, such as bone marrow mesenchymal stem cells (MSCs). CLINICAL RELEVANCE: The availability of an easily accessible and reproducible cell source may greatly facilitate the development of new cell-based therapies for regenerative medicine applications in the musculoskeletal system. PMID: 20625952 [PubMed - as supplied by publisher] | | |
| Thermoresponsive poly(N-vinylcaprolactam) cryogels: synthesis and its biophysical evaluation for tissue engineering applications.
July 14, 2010 at 6:21 AM
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| | Thermoresponsive poly(N-vinylcaprolactam) cryogels: synthesis and its biophysical evaluation for tissue engineering applications. J Mater Sci Mater Med. 2010 Jul 13; Authors: Srivastava A, Kumar A The thermoresponsive poly(N-vinylcaprolactam) (PVCl) based cryogel network were synthesized and characterized with respect to physical and biological properties. The PVCl cryogel crosslinked with polyethylene glycol-diacrylate (PEGda) was synthesized in 1% dimethyl sulfoxide containing aqueous medium at -12 degrees C for 12-14 h. The cryogel synthesized in this manner were highly spongy in nature and can absorb water in its porous network. These polymeric cryogel networks have good physical morphology as confirmed by scanning electron microscopy. The estimated porosity of these cryogels was 90% as demonstrated by various methods based on absorption of water and cyclohexane. The median pore diameter and surface area was 30 mum and 2.0253 m(2)/g, respectively as confirmed by analysis on mercury porosimeter. These materials can interact with biological system without any cytotoxic effects. Change in temperature influenced the adsorption of fetal bovine serum (FBS) on PVCl scaffold which showed maximum protein adsorption at 37 degrees C, as compared to that at 25 degrees C. Furthermore, the fibroblast cell adhesion studies showed the potential of these PVCl based cryogels as tissue engineering scaffolds. PMID: 20625836 [PubMed - as supplied by publisher] | | |
| Cell Compatibility of Fibrin Sealants:In Vitro Study with Cells Involved in Soft Tissue Repair.
July 14, 2010 at 6:21 AM
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| | Cell Compatibility of Fibrin Sealants:In Vitro Study with Cells Involved in Soft Tissue Repair. J Biomater Appl. 2010 Jul 12; Authors: Macasev D, Diorio JP, Gugerell A, Goppelt A, Gulle H, Bittner M Fibrin sealants can be used to support tissue regeneration or as vehicles for delivery of cells in tissue engineering. Differences in the composition of fibrin sealants, however, could determine the success of such applications. The results presented in this article show clear differences between Fibrin sealant A (FS A) clots and Fibrin sealant B (FS B) clots with respect to their compatibility with primary human cells involved in soft tissue repair. FS A clots, which are characterized by a physiological coarse fibrin structure, promoted attachment, spreading, and proliferation of keratinocytes, fibroblasts, and endothelial cells. In contrast, FS B clots displaying a fine to medium clot structure failed to support spreading of all three cell types. Adhesion of keratinocytes was decreased on FS B clots compared to FS A clots after 3 h incubation, whereas number of attached fibroblasts and endothelial cells was initially comparable between the two fibrin sealants. However, all three cell types proliferated on FS A clots but no sustained proliferation was detected on FS B clots. We further demonstrate that the observed differences between FS A and B clots are partly based upon 1 M sodium chloride extractable constituents, like thrombin, and partly on nonextractable constituents or the fibrin structure. In conclusion, our in vitro results demonstrate that FS A clots serve as a provisional matrix that encourages adhesion and growth of keratinocytes, fibroblasts, and endothelial cells. Therefore, FS A seems to be well suited for applications in tissue engineering. PMID: 20624847 [PubMed - as supplied by publisher] | | |
| Osteoclast and Osteoblast Activities on Carbonate Apatite Plates in Cell Cultures.
July 14, 2010 at 6:21 AM
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| | Osteoclast and Osteoblast Activities on Carbonate Apatite Plates in Cell Cultures. J Biomater Appl. 2010 Jul 12; Authors: Kanayama K, Sriarj W, Shimokawa H, Ohya K, Doi Y, Shibutani T Previous studies have demonstrated that carbonate apatite (CA) is superior to hydroxyapatite (HA) and beta-tricalciumphosphate (beta-TCP) with regard to osteoclastic resorption, but evidence on osteoclast and osteoblast response remains controversial. In the present study, the expression of bone related mRNA is examined on CA, HA, beta-TCP, and titanium plates. ICR mouse osteoblast cells are cocultured with ICR mouse bone marrow cells. Crude osteoclast-like cell-rich suspensions are then seeded onto plates and cultured for 48 h. Total RNA is extracted and mRNA expression is examined by real-time RT-PCR. Amounts of vacuolar-type ATPase, cathepsin K, and TRAP mRNA are significantly greater on CA than on the other plates. The amount of osteoprotegerin mRNA is significantly greater on CA than on the other plates. RANKL mRNA expression, which is generally regarded as an osteoblast maker, varies with material, but shows no significant differences between CA and the other plates. The formation and activity of osteoclasts is greater with CA than with the other plates. Thus, CA is superior to beta-TCP as a bioresorbable bone substitute for tissue engineering. PMID: 20624844 [PubMed - as supplied by publisher] | | |
| Platelet-rich fibrin modulates the expression of extracellular signal-regulated protein kinase and osteoprotegerin in human osteoblasts.
July 14, 2010 at 6:21 AM
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| | Platelet-rich fibrin modulates the expression of extracellular signal-regulated protein kinase and osteoprotegerin in human osteoblasts. J Biomed Mater Res A. 2010 Jul 8; Authors: Chang IC, Tsai CH, Chang YC Platelet-rich fibrin (PRF) by Choukroun's technique is produced in a totally natural manner, without using anticoagulant during blood harvest nor bovine thrombin and calcium chloride for platelet activation and fibrin polymerization. When delicately pressed between two gauzes, the PRF clot becomes a strong membrane with high potential in clinical application and tissue engineering. In this study, blood collection was carried out from healthy volunteers. Osteoblast cell line U2OS was used to evaluate the cell proliferation resulting from PRF by using colorimetric assay. Western blot was employed to evaluate the expression of phosphorylated extracellular signal-regulated protein kinase (p-ERK), receptor activator of nuclear factor-kappa B ligand (RANKL), and osteoprotegerin (OPG) in U2OS cells. PRF was found to increase osteoblast proliferation during 5 day incubation period (p < 0.05). PRF was found to increase ERK phosphorylation in U2OS cells (p < 0.05). OPG was significantly elevated by the stimulation with PRF (p < 0.05). However, there was no significant change in RANKL expression (p > 0.05). Taken together, PRF can stimulate osteoblasts proliferation. The activation of p-ERK and OPG expression by PRF suggests a potential role for new bone formation. The application of PRF may provide the benefit for the bone regeneration. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20623670 [PubMed - as supplied by publisher] | | |
| Induced pluripotent stem cells: A new era for hepatology.
July 14, 2010 at 6:21 AM
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| | Induced pluripotent stem cells: A new era for hepatology. J Hepatol. 2010 Jun 22; Authors: Asgari S, Pournasr B, Salekdeh GH, Ghodsizadeh A, Ott M, Baharvand H Stem cell transplantation has been proposed as an attractive alternative approach to restore liver mass and function. Recent progress has been reported on the generation of induced pluripotent stem (iPS) cells from somatic cells. Human-iPS cells can be differentiated towards the hepatic lineage which presents possibilities for improving research on diseases, drug development, tissue engineering, the development of bio-artificial livers, and a foundation for producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. This focused review will discuss how human iPS cell advances are likely to have an impact on hepatology. PMID: 20621379 [PubMed - as supplied by publisher] | | |
| Human Adipose Tissue-Derived Adult Stem Cells Can Lead to Multiorgan Engraftment.
July 14, 2010 at 6:21 AM
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| | Human Adipose Tissue-Derived Adult Stem Cells Can Lead to Multiorgan Engraftment. Transplant Proc. 2010 Jun;42(5):1849-1856 Authors: Fang B, Li Y, Song Y, Li N, Cao Y, Wei X, Lin Q, Zhao RC Recent studies have demonstrated the existence of a population of adipose tissue-derived adult stem cells that can undergo multilineage differentiation in vitro; however, it is unclear whether these cells maintain their multilineage differentiation in vivo. The objective of the present study was to examine the in vivo characteristics and behavior of a potential population of human adipose tissue-derived adult stem cells. Herein, we demonstrate that human adipose tissue-derived adult stem cells differentiate into the epithelium of the gastrointestinal tract, liver, and bronchi, and an endothelial lineage after transplantation into irradiated nonobese mice with diabetes or severe combined immunodeficiency. These findings may contribute to clinical tissue repair after injury. PMID: 20620536 [PubMed - as supplied by publisher] | | |
| Differential distribution of structural components and hydration in aortic and pulmonary heart valve conduits: Impact of detergent-based cell removal.
July 14, 2010 at 6:21 AM
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| | Differential distribution of structural components and hydration in aortic and pulmonary heart valve conduits: Impact of detergent-based cell removal. Acta Biomater. 2010 Jul 7; Authors: Naso F, Gandaglia A, Formato M, Cigliano A, Lepedda AJ, Gerosa G, Spina M Evaluation of the physiological performance of biological scaffolds for tissue-engineering applications has been mostly based on biophysical and morphological methods, with limited attention to the quantitative contribution of main structural components to native and/or treated valve assemblies. In the present study, quantization was addressed to porcine leaflet, sinus and adjacent wall of aortic and pulmonary valved conduits before and after detergent-based cell removal. Collagen, elastin, glycosaminoglycan, lipid and water contents were expressed in terms of relative concentration and volume fraction in order to assess their effective contribution to the native tissue and to changes following decellularization procedures. Main findings were recognition of unexpectedly large water and underestimated collagen content; differential distribution of elastin between the sectors and of glycosaminoglycan along the conduits; and pulmonary scaffold destabilization upon cell removal, not found in the aortic case. Simultaneous investigation allowed consistent comparison between native and decellularized tissues and added analytical knowledge crucial for designing realistic constitutive models. We have provided a quantitative structural foundation for earlier biomechanical findings in pulmonary leaflets and the basis for validation of theoretical assumptions still lacking support of experimental evidence in both conduits. Future insights into distribution of load-bearing components in human conduits are likely to provide indications important to the optimization of surgical positioning of valvular grafts. PMID: 20620247 [PubMed - as supplied by publisher] | | |
| Predicting bulk mechanical properties of cellularized collagen gels using multiphoton microscopy.
July 14, 2010 at 6:21 AM
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| | Predicting bulk mechanical properties of cellularized collagen gels using multiphoton microscopy. Acta Biomater. 2010 Jul 7; Authors: Raub C, Putnam A, Tromberg B, George SC Cellularized collagen gels are a common model in tissue engineering, but the relationship between the microstructure and bulk mechanical properties is only partially understood. Multiphoton microscopy (MPM) is an ideal non-invasive tool to examine collagen microstructure, cellularity and crosslink content in these gels. In order to identify robust image parameters that characterize microstructural determinants of the bulk elastic modulus, we performed serial MPM and mechanical tests on acellular and cellularized (normal human lung fibroblasts) collagen hydrogels, before and after glutaraldehyde crosslinking. Following gel contraction over sixteen days, cellularized collagen gel content approached that of native connective tissues ( approximately 200 mg/ml). Young's modulus (E) measurements from acellular collagen gels (range 0.5-12 kPa) exhibited a power-law concentration dependence (range 3-9 mg/ml) with exponents from 2.1-2.2, similar to other semiflexible biopolymer networks such as fibrin and actin. In contrast, cellularized collagen gel stiffness (range 0.5-27 kPa) produced concentration-dependent exponents of 0.7 uncrosslinked and 1.1 crosslinked (range approximately 5-200 mg/ml). The variation in E of cellularized collagen hydrogels can be explained by a power-law dependence on robust image parameters: either the second harmonic generation (SHG) and two-photon fluorescence (TPF) (matrix component) skewness (R(2) = 0.75, exponents of -1.0 and -0.6, respectively); or alternately the SHG and TPF (matrix component) speckle contrast (R(2) = 0.83, exponents of -0.7 and -1.8, respectively). Image parameters based on the cellular component of TPF signal did not improve the fits. The concentration dependence of E suggests enhanced stress relaxation in cellularized versus acellular gels. SHG and TPF image skewness and speckle contrast from cellularized collagen gels can predict E by capturing mechanically relevant information on collagen fiber, cell and crosslink density. PMID: 20620246 [PubMed - as supplied by publisher] | | |
| Virtual topological optimisation of scaffolds for rapid prototyping.
July 14, 2010 at 6:21 AM
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| | Virtual topological optimisation of scaffolds for rapid prototyping. Med Eng Phys. 2010 Jul 8; Authors: Almeida HD, da Silva Bártolo PJ Advanced additive techniques are now being developed to fabricate scaffolds with controlled architecture for tissue engineering. These techniques combine computer-aided design (CAD) with computer-aided manufacturing (CAM) tools to produce three-dimensional structures layer by layer in a multitude of materials. Actual prediction of the effective mechanical properties of scaffolds produced by additive technologies, is very important for tissue engineering applications. A novel computer based technique for scaffold design is topological optimisation. Topological optimisation is a form of "shape" optimisation, usually referred to as "layout" optimisation. The goal of topological optimisation is to find the best use of material for a body that is subjected to either a single load or a multiple load distribution. This paper proposes a topological optimisation scheme in order to obtain the ideal topological architectures of scaffolds, maximising its mechanical behaviour. PMID: 20620093 [PubMed - as supplied by publisher] | | |
| Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells.
July 14, 2010 at 6:21 AM
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| | Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells. Biomaterials. 2010 Sep;31(27):6968-6980 Authors: Toh WS, Lee EH, Guo XM, Chan JK, Yeow CH, Choo AB, Cao T Human embryonic stem cells (hESCs) have the potential to offer a virtually unlimited source of chondrogenic cells for use in cartilage repair and regeneration. We have recently shown that expandable chondrogenic cells can be derived from hESCs under selective growth factor-responsive conditions. In this study, we explore the potential of these hESC-derived chondrogenic cells to produce an extracellular matrix (ECM)-enriched cartilaginous tissue construct when cultured in hyaluronic acid (HA)-based hydrogel, and further investigated the long-term reparative ability of the resulting hESC-derived chondrogenic cell-engineered cartilage (HCCEC) in an osteochondral defect model. We hypothesized that HCCEC can provide a functional template capable of undergoing orderly remodeling during the repair of critical-sized osteochondral defects (1.5 mm in diameter, 1 mm depth into the subchondral bone) in a rat model. In the process of repair, we observed an orderly spatial-temporal remodeling of HCCEC over 12 weeks into osteochondral tissue, with characteristic architectural features including a hyaline-like neocartilage layer with good surface regularity and complete integration with the adjacent host cartilage and a regenerated subchondral bone. By 12 weeks, the HCCEC-regenerated osteochondral tissue resembled closely that of age-matched unoperated native control, while only fibrous tissue filled in the control defects which left empty or treated with hydrogel alone. Here we demonstrate that transplanted hESC-derived chondrogenic cells maintain long-term viability with no evidence of tumorigenicity, providing a safe, highly-efficient and practical strategy of applying hESCs for cartilage tissue engineering. PMID: 20619789 [PubMed - as supplied by publisher] | | |
| Fabrication of Functional Cardiac, Skeletal, and Smooth Muscle Pumps In Vitro.
July 14, 2010 at 6:21 AM
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| | Fabrication of Functional Cardiac, Skeletal, and Smooth Muscle Pumps In Vitro. Artif Organs. 2010 Jul 4; Authors: Evers R, Khait L, Birla RK Abstract Cardiovascular disease is one of the leading causes of death in the United States, and new treatments need to be developed in order to provide novel therapies. Tissue engineering aims to develop biologic substitutes that restore tissue function. The purpose of the current study was to construct cell-based pumps, which can be viewed as biologic left ventricular assist devices. The pumps were fabricated by culturing cardiac, skeletal, and smooth muscle cells within a fibrin gel and then each 3-D tissue construct was wrapped around a decellularized rodent aorta. We described the methodology for pump fabrication along with functional performance metric, determined by the intra-luminal pressure. In addition, histologic evaluation showed a concentric organization of components, with the muscle cells positioned on the outermost surface, followed by the fibrin gel and the decellularized aorta formed the innermost layer. Though early in development, cell-based muscle pumps have tremendous potential to be used for basic and applied research, and with further development, can be used clinically as cell-based left ventricular assist devices. PMID: 20618224 [PubMed - as supplied by publisher] | | |
| Fabricating tissue engineering scaffolds for simultaneous cell growth and drug delivery.
July 14, 2010 at 6:21 AM
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| | Fabricating tissue engineering scaffolds for simultaneous cell growth and drug delivery. Curr Pharm Des. 2010;16(21):2388-94 Authors: Chen W, Tabata Y, Tong YW The formulation and fabrication methods for several types of tissue engineering scaffolds with drug delivery capabilities are presented in this review. Tissue engineered constructs are temporary substitutes developed to treat damaged or lost tissue. One key component of such constructs is scaffolds that are often developed to mimic the extra cellular matrix (ECM). As natural ECM contains biomolecules to support proper growth and function of cells, inclusion of these biomolecular cues have been shown to be necessary for proper cell growth and function in tissue engineering. Thus, an effective tissue engineering scaffold should provide such biomolecular cues. This can be achieved through drug delivery in scaffolds. Studies have shown that drug delivery systems are necessary to protect drugs, and provide sustained drug release that is often needed for effective therapy. The tissue engineering features of 4 scaffold types are described, including films, hydrogels, fibers, and microspheres/nanospheres. Fabrication techniques and drug encapsulation methods for these scaffolds are reviewed in addition to some observations arising from the use of these techniques and methods. PMID: 20618159 [PubMed - in process] | | |
| EFFECT OF PI3K, ERK1/2 AND P38 MAPK INHIBITION ON OSTEOGENIC DIFFERENTIATION OF MUSCLE-DERIVED STEM CELLS.
July 14, 2010 at 6:21 AM
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| | EFFECT OF PI3K, ERK1/2 AND P38 MAPK INHIBITION ON OSTEOGENIC DIFFERENTIATION OF MUSCLE-DERIVED STEM CELLS. Tissue Eng Part A. 2010 Jul 9; Authors: Payne KA, Meszaros LB, Phillippi JA, Huard J Skeletal muscle-derived stem cells (MDSCs) can undergo osteogenesis when treated with bone morphogenetic proteins (BMPs), making them a potential cell source for bone tissue engineering. The signaling pathways that regulate BMP4-induced osteogenesis in MDSCs are not well understood, although they may provide a means to better regulate differentiation during bone regeneration. The objective of this study was to characterize the signaling pathways involved in the BMP4-induced osteogenesis of MDSCs. Cells were treated with BMP4 and specific inhibitors to the ERK1/2, p38 MAPK and PI3K pathways (PD98059, SB203580 and Ly294002, respectively). Cellular proliferation, expression of osteoblast-related genes, alkaline phosphatase (ALP) activity, and tissue mineralization were measured to determine the role of each pathway in the osteogenic differentiation of MDSCs. Inhibition of the ERK1/2 pathway increased ALP activity and mineralization, while inhibition of the p38 MAPK pathway decreased osteogenesis, suggesting opposing roles of these pathways in the BMP4-induced osteogenesis of MDSCs. Inhibition of the PI3K pathway significantly increased mineralization by MDSCs. These findings highlight the involvement of the ERK1/2, p38 MAPK and PI3K pathways in opposing capacities in MDSC differentiation and warrant further investigation, as it may identify novel therapeutic targets for the development of stem cell-based therapies for bone tissue engineering. PMID: 20617875 [PubMed - as supplied by publisher] | | | | 
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