|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | The California stem cell agency is about ready to jump into the publishing business.
The $3 billion, taxpayer-financed enterprise on Monday received three responses to its proposal to spend $600,000 over the next three years to start a new, online stem cell research journal. The enterprises seeking the seed money are AlphaMed Press of Durham, N.C., the International Society for Stem Cell | | | | | | | | | | | | | | | | | | | | | | | | | (31)P and (13)C solid-state NMR spectroscopy to study collagen synthesis and biomineralization in polymer-based bone implants. NMR Biomed. 2011 Jan 12; Authors: Weber F, Böhme J, Scheidt HA, Gründer W, Rammelt S, Hacker M, Schulz-Siegmund M, Huster D A combination of solid-state NMR spectroscopy and MRI was used to evaluate the formation of extracellular matrix in poly(D,L-lactide-co-glycolide) (PLGA) bone implants. Porous PLGA scaffolds were implanted into rat tibiae and analysed after 2, 4 or 8 weeks. MRI clearly delineated the implants within the cancellous bone. Differences in the trabecular structure of the implanted material and native bone were demonstrated. In addition, implants were analyzed by solid-state NMR spectroscopy under magic angle spinning. (13)C NMR spectra showed the unambiguous signature of collagen formed in the scaffolds, but also the characteristic signals of the PLGA matrix, indicating that resorption was not complete after 8 weeks. Furthermore, (31)P NMR spectroscopy detected the inorganic component of the matrix, which is composed of bioapatite. (31)P NMR spectra were quantified and this analysis revealed that the amount of inorganic extracellular matrix formed de novo was significantly lower than in native bone. This demonstrates that solid-state NMR spectroscopy, in particular in combination with MRI, can provide useful information on the composition and structure of the extracellular matrix, and serve as a tool to evaluate the quality of tissue engineering strategies. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21226078 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Controlling the porosity of fibrous scaffolds by modulating the fiber diameter and packing density. J Biomed Mater Res A. 2011 Jan 10; Authors: Soliman S, Sant S, Nichol JW, Khabiry M, Traversa E, Khademhosseini A Porosity has been shown to be a key determinant of the success of tissue engineered scaffolds. A high degree of porosity and an appropriate pore size are necessary to provide adequate space for cell spreading and migration as well as to allow for proper exchange of nutrients and waste between the scaffold and the surrounding environment. Electrospun scaffolds offer an attractive approach for mimicking the natural extracellular matrix (ECM) for tissue engineering applications. The efficacy of electrospinning is likely to depend on the interaction between cells and the geometric features and physicochemical composition of the scaffold. A major problem in electrospinning is the tendency of fibers to accumulate densely, resulting in poor porosity and small pore size. The porosity and pore sizes in the electrospun scaffolds are mainly dependent on the fiber diameter and their packing density. Here we report a method of modulating porosity in three dimensional (3D) scaffolds by simultaneously tuning the fiber diameter and the fiber packing density. Nonwoven poly(ε-caprolactone) mats were formed by electrospinning under various conditions to generate sparse or highly dense micro- and nanofibrous scaffolds and characterized for their physicochemical and biological properties. We found that microfibers with low packing density resulted in improved cell viability, proliferation and infiltration compared to tightly packed scaffolds. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: , 2011. PMID: 21225711 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Diffusion of biologically relevant molecules through gel-like tissue scaffolds. Biotechnol Prog. 2010 Oct 13; Authors: Roberts SJ, Tomlins PE, Faruqui N, Robinson JA Encapsulation of living cells into gel-like matrices that are capable of maintaining their viability over an extended time period is starting to play a major role in medicine in applications such as, cell-based sensors, cellular therapy, and tissue engineering. The permeability of nutrients and waste products through these matrices is critical to their performance. In this article, we report a methodology for selecting scaffolds with different permeabilities and surface area/volume ratios that can be used to house a 3D cell aggregate. Such a system can be modeled if the consumption or production rates for metabolites and waste products, respectively and the diffusion coefficients of these solutes in culture medium and the encapsulating gel matrix are known. A transient finite volume mass diffusion model, based on Fick's law, is derived where the consumption of a solute by the cells is modeled through a source term. The results show that the "performance" of cell-doped gel is critically dependent on the rate at which cells consume key molecules e.g., glucose. Pragmatically, the model also provides insight as to how many cells a given gel geometry and structure can support. The approach used applies to any porous structure where mass transport occurs through diffusion. © 2011 Crown Copyright Biotechnol. Prog.,, 2011. PMID: 21225696 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Application of conductive polymers, scaffolds and electrical stimulation for nerve tissue engineering. J Tissue Eng Regen Med. 2011 Jan 10; Authors: Ghasemi-Mobarakeh L, Prabhakaran MP, Morshed M, Nasr-Esfahani MH, Baharvand H, Kiani S, Al-Deyab SS, Ramakrishna S Among the numerous attempts to integrate tissue engineering concepts into strategies to repair nearly all parts of the body, neuronal repair stands out. This is partially due to the complexity of the nervous anatomical system, its functioning and the inefficiency of conventional repair approaches, which are based on single components of either biomaterials or cells alone. Electrical stimulation has been shown to enhance the nerve regeneration process and this consequently makes the use of electrically conductive polymers very attractive for the construction of scaffolds for nerve tissue engineering. In this review, by taking into consideration the electrical properties of nerve cells and the effect of electrical stimulation on nerve cells, we discuss the most commonly utilized conductive polymers, polypyrrole (PPy) and polyaniline (PANI), along with their design and modifications, thus making them suitable scaffolds for nerve tissue engineering. Other electrospun, composite, conductive scaffolds, such as PANI/gelatin and PPy/poly(ε-caprolactone), with or without electrical stimulation, are also discussed. Different procedures of electrical stimulation which have been used in tissue engineering, with examples on their specific applications in tissue engineering, are also discussed. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21225613 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Controlled gelation and degradation rates of injectable hyaluronic acid-based hydrogels through a double crosslinking strategy. J Tissue Eng Regen Med. 2011 Jan 10; Authors: Tan H, Li H, Rubin JP, Marra KG Various biodegradable hydrogels have been employed as injectable scaffolds for tissue engineering and drug delivery. We report a double-crosslinking strategy of biocompatible and biodegradable hydrogels derived from aminated and oxidized hyaluronic acid (HA) with genipin (GP), a compound naturally derived from the gardenia fruit. Fast gelation is attributed to the Schiff-base reaction between amino and aldehyde groups of polysaccharide derivatives, and the subsequent crosslinking with GP results in ideal biodegradability and mechanical properties. The gelation time, morphology, equilibrium swelling, compressive modulus and degradation of double-crosslinked hydrogels were examined. The double crosslinked hydrogels were examined in vivo via subcutaneous injection into a mouse model. Histological results indicated favourable biocompatility, as revealed by an absence of neutrophils and macrophages. These studies demonstrate that double-crosslinked HA hydrogels are potentially useful as injectable, biodegradable hydrogels in tissue-engineering applications. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21225597 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Chondrocytes and bone marrow-derived mesenchymal stem cells undergoing chondrogenesis in agarose hydrogels of solid and channelled architectures respond differentially to dynamic culture conditions. J Tissue Eng Regen Med. 2011 Jan 10; Authors: Sheehy EJ, Buckley CT, Kelly DJ The objective of this study was to investigate how a combination of different scaffold architectures and rotational culture would influence the functional properties of thick cartilaginous tissues engineered using either chondrocytes or bone marrow-derived mesenchymal stem cells (BM-MSCs). Expanded porcine chondrocytes and BM-MSCs were suspended in 2% agarose and cast in custom-designed moulds to produce either regular solid or channelled construct cylinders. The study consisted of three seperate experimental arms. First, chondrocyte and BM-MSC constructs were cultured in free swelling conditions for 9 weeks. Second, constructs were subjected to rotational culture for a period of 3 weeks. Finally, BM-MSC-seeded constructs were subjected to delayed rotational culture, in which constructs were first cultured for 3 weeks in free swelling conditions, followed by an additional 3 weeks in rotating culture conditions. Constructs were supplemented with TGFβ3 during the first 3 weeks of all experiments. The introduction of channels alone had little effect on the spatial patterns of tissue accumulation in either chondrocyte- or BM-MSC-seeded constructs. The two cell types responded differentially to rotational culture, resulting in the formation of a more homogeneous tissue in chondrocyte-seeded constructs, but significantly inhibiting chondrogenesis of BM-MSCs. This inhibition of chondrogenesis in response to dynamic culture conditions was not observed if BM-MSC-seeded constructs were first maintained in free swelling conditions for 3 weeks prior to rotation. The results of this study demonstrate that bioreactor culture conditions that are beneficial for chondrocyte-based cartilage tissue engineering may be suboptimal for BM-MSCs. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21225596 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Towards in vitro vascularisation of collagen-GAG scaffolds. Eur Cell Mater. 2011;21:15-30 Authors: Duffy GP, McFadden TM, Byrne EM, Gill SL, Farrell E, O'Brien FJ Collagen-glycosaminoglycan scaffolds that have been used clinically for skin regeneration have also shown significant promise for other applications in tissue engineering. However, regeneration of thicker tissues with the aid of implanted biomaterials is likely to depend on, or be accelerated by, the ability to establish rapid vascularisation of the implant. The present study aims to establish a nascent vascular network in vitro within a CG scaffold as a first step towards that goal. Mesenchymal stem cells (MSCs) were chosen as primary vasculogenic candidate cells and a culture medium that promoted maximal network formation on Matrigel by these cells was selected. MSCs seeded in the CG scaffold formed networks of cord-like structures after one to two weeks in the presence of the vasculogenic medium; similar structures were formed by aortic endothelial cells (ECs) cultured for comparison. Gene expression analysis suggested that the MSCs began to adopt an endothelial phenotype, with RNA for PECAM and VCAM rising while that for alpha-smooth muscle actin fell. However there was no increase in Tie-2 and vWF expression. Addition of smooth muscle cells (SMCs) as a potential perivascular stabilising component did not have a noticeable effect on MSC-derived networks, although it enhanced EC-derived structures. PMID: 21225592 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Photocontrol of cell adhesion on amino-bearing surfaces by reversible conjugation of poly(ethylene glycol) via a photocleavable linker. Phys Chem Chem Phys. 2011 Jan 11; Authors: Kaneko S, Nakayama H, Yoshino Y, Fushimi D, Yamaguchi K, Horiike Y, Nakanishi J Dynamic control of cell adhesion on substrates is a useful technology in tissue engineering and basic biology. This paper describes a method for the control of cell adhesion on amino-bearing surfaces by reversible conjugation of an anti-fouling polymer, poly(ethylene glycol) (PEG), via a newly developed photocleavable linker, 1-(5-methoxy-2-nitro-4-prop-2-ynyloxyphenyl)ethyl N-succinimidyl carbonate (1). This molecule has alkyne and succinimidyl carbonate at each end, which are connected by photocleavable 2-nitrobenzyl ester. Under this molecular design, the molecule crosslinked azides and amines, whose linkage cleaved upon application of near-UV light. By using aminosilanised glass and silicon as model substrates, we studied their reversible surface modification with PEG-azide (M(w) = 5000) based on contact angle measurements, ellipsometry, and AFM morphological observations. Protein adsorption and cell adhesion dramatically changed by PEGylation and the following irradiation, which can be used for cellular patterning. Also, the capability of the substrate to change cell adhesiveness by photoirradiation during cell cultivation was demonstrated by inducing cell migration. We believe this method will be useful for dynamic patterning of cells on protein-based scaffolds. PMID: 21225032 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Functional Aliphatic Polyesters for Biomedical and Pharmaceutical Applications. J Control Release. 2011 Jan 8; Authors: Seyednejad H, Ghassemi AH, van Nostrum CF, Vermonden T, Hennink WE Functional aliphatic polyesters are biodegradable polymers with many possibilities to tune physico-chemical characteristics such as hydrophilicity and degradation rate as compared to traditional polyesters (e.g. PLLA, PLGA and PCL), making the materials suitable for drug delivery or as scaffolds for tissue engineering. Lately, a large number of polyesters have been synthesized by homopolymerization of functionalized monomers or co-polymerization with other monomers mainly via ring-opening polymerization (ROP) of cyclic esters. This review presents the recent trends in the synthesis of these materials and their application for protein delivery and tissue engineering. PMID: 21223989 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Mechanism of ginsenoside Rg1 in the delayed senescence of hematopoietic stem cell.] Zhonghua Yi Xue Za Zhi. 2010 Dec;90(48):3421-3425 Authors: Zhou Y, Yang B, Jiang R, Yao X, Wang YP OBJECTIVE: To investigate the underlying mechanism of ginsenoside Rg1 in the regulation of hematopoietic stem cell (HSC) senescence so as to provide the theoretic and experimental foundations for searching the methods of how to delay its senescence. METHODS: Sca-1(+)HSC was isolated by magnetic cell sorting (MACS) and divided into control, aged, Rg1, Rg1 treatment aged and Rg1 delayed aged groups. The cellular changes were observed by senescence-associated β-galactosidase (SA-β-Gal) staining. And cell cycle assay and culture of mixed hematopoietic progenitor cell were used to investigate the effect of ginsenoside Rg1 to delay Sca-1(+)HSC senescence. The expressions of p16(INK4a), p19(Arf), p53 and p21(Cip1/Waf1) mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). The expressions of p16(INK4a), p21(Cip1/Waf1), cyclinD1, cyclinE, CDK2 and CDK4 protein were examined by Western blot. RESULTS: In the Rg1 treatment and delayed aged groups, the percentage of positive SA-β-Gal-expressing cells was lower than that of the aged group [30.1% ± 2.4%, 21.5% ± 2.8% vs 69.5% ± 5.0%]; the number of cells in G(1) phase was lower than that of the aged group [81.4% ± 1.2%, 78.2% ± 1.4% vs 87.5% ± 4.0%]; but the number of colony for the mixed hematopoietic progenitor was higher than that of the aged group [(8.0 ± 2.2)/10(4) Sca-1(+)HSC, (9.2 ± 1.8)/10(4) Sca-1(+)HSC vs (3.0 ± 1.6)/10(4) Sca-1(+)HSC]. As compared with the aged group, the expressions of p16(INK4a), p19(Arf), p53, p21(Cip1/Waf1)mRNA and p16(INK4a), p21(Cip1/Waf1), cyclinD1 protein were down-regulated (all P < 0.01) while the expressions of CDK4, CDK2 and cyclinE protein up-regulated in Rg1 treatment aged and Rg1 delayed aged groups (all P < 0.01). The changes of the Rg1 delayed aged group were significantly marked than those of the Rg1 treatment aged group. CONCLUSIONS: Rg1 can effectively delay the t-BHP-induced senescence of HSCs. Both p16(INK4a)-Rb and p19(Arf)-p53-p21(Cip/Waf1) may play an important role in the signaling pathway. PMID: 21223818 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Salivary gland progenitor cell biology provides a rationale for therapeutic salivary gland regeneration. Oral Dis. 2011 Jan 11; Authors: Lombaert I, Knox S, Hoffman M Oral Diseases (2011) An irreversible loss of salivary gland function often occurs in humans after removal of salivary tumors, after therapeutic radiation of head and neck tumors, as a result of Sjögren's syndrome and in genetic syndromes affecting gland development. The permanent loss of gland function impairs the oral health of these patients and broadly affects their quality of life. The regeneration of functional salivary gland tissue is thus an important therapeutic goal for the field of regenerative medicine and will likely involve stem/progenitor cell biology and/or tissue engineering approaches. Recent reports demonstrate how both innervation of the salivary gland epithelium and certain growth factors influence progenitor cell growth during mouse salivary gland development. These advances in our understanding suggest that developmental mechanisms of mouse salivary gland development may provide a paradigm for postnatal regeneration of both mice and human salivary glands. Herein, we will discuss the developmental mechanisms that influence progenitor cell biology and the implications for salivary gland regeneration. PMID: 21223454 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal Stromal Cells: Past, Present, and Future. Vet Surg. 2011 Jan 11; Authors: Spencer ND, Gimble JM, Lopez MJ Adult mesenchymal stromal cells are plastic-adherent cells that are self-renewing and have the capacity to differentiate into various tissue specific lineages. Stromal cells were initially discovered over 100 years ago and substantial insight into stromal cell identification, isolation, characterization, and differentiation has been made, including efforts to elucidate the factors involved in stromal cell differentiation. Stromal cells have immune privilege and thus are attractive candidates for tissue engineering and regenerative medicine applications. Positive results from a number of recent investigations support the use of adult mesenchymal stromal cells for clinical application. This review article provides a brief overview of past, present, and future stromal cell technology. PMID: 21223314 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Tissue Engineering for Post-Myocardial Infarction Ventricular Remodeling. Mini Rev Med Chem. 2011 Jan 11; Authors: Kolettis TM, Vilaeti A, Dimos K, Tsitou N, Agathopoulos S Myocardial tissue engineering involves the design of biomaterial scaffolds, aiming at regenerating necrotic myocardium after myocardial infarction. Biomaterials provide mechanical support to the infarct area and they can be used as vehicles for sustained and controlled local administration of cells and growth factors. Although promising results have been reported in experimental studies, many issues need to be addressed before human use. PMID: 21222573 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Biophysics and dynamics of natural and engineered stem cell microenvironments. Wiley Interdiscip Rev Syst Biol Med. 2010 Jan-Feb;2(1):49-64 Authors: Keung AJ, Healy KE, Kumar S, Schaffer DV Stem cells are defined by their ability to self-renew and to differentiate into one or more mature lineages, and they reside within natural niches in many types of adult and embryonic tissues that present them with complex signals to regulate these two hallmark properties. The diverse nature of these in vivo microenvironments raises important questions about the microenvironmental cues regulating stem cell plasticity, and the stem cell field has built a strong foundation of knowledge on the biochemical identities and regulatory effects of the soluble, cellular, and extracellular matrix factors surrounding stem cells through the isolation and culture of stem cells in vitro within microenvironments that, in effect, emulate the properties of the natural niche. Recent work, however, has expanded the field's perspective to include biophysical and dynamic characteristics of the microenvironment. These include biomechanical characteristics such as elastic modulus, shear force, and cyclic strain; architectural properties such as geometry, topography, and dimensionality; and dynamic structures and ligand profiles. We will review how these microenvironmental characteristics have been shown to regulate stem cell fate and discuss future research directions that may help expand our current understanding of stem cell biology and aid its application to regenerative medicine. PMID: 20836010 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Surgical ventricular restoration with a cell- and cytokine-seeded biodegradable scaffold. Biomaterials. 2010 Oct;31(30):7684-94 Authors: Miyagi Y, Zeng F, Huang XP, Foltz WD, Wu J, Mihic A, Yau TM, Weisel RD, Li RK Late after a myocardial infarction (MI), surgical ventricular restoration (SVR) can reduce left ventricular volumes, but an enhanced cardiac patch may be required to restore function. We developed a new, biodegradable patch (modified gelfoam, MGF) consisting of a spongy inner core (gelfoam) to encourage cell engraftment and an outer coating (poly epsilon-caprolactone) to provide sufficient strength to permit ventricular repair. Two weeks after coronary ligation in rats, SVR was performed using one of the following: gelfoam, MGF, MGF patches with hydrogel alone, or with hydrogel and cytokines (stem cell factor, stromal cell-derived factor-1alpha), bone marrow mesenchymal stem cells, or both. Cardiac function and morphology were evaluated by echocardiography, conduction catheterization, magnetic resonance imaging, and histology. Animals whose hearts were repaired with untreated gelfoam died of ventricular rupture. The MGF groups had significantly improved myocardial systolic function vs. MI controls. Enhancement with cytokines and/or cells promoted more alpha-smooth muscle actin-positive cells, more capillaries, greater wall thickness, a more ellipsoid shape, greater fractional shortening, and better-preserved systolic elastance than MGF alone. This combination of the new, reinforced, biodegradable biomaterial and cytokine/cell treatment created a viable tissue after SVR and produced better functional outcomes than un-reinforced gelfoam or MGF alone. PMID: 20659765 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | [Signal pathways in breast cancer stem cells and the targeted stem cell therapy.] Zhonghua Zhong Liu Za Zhi. 2010 Dec;32(12):881-885 Authors: Ma Y, Wang HX PMID: 21223793 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Comparison of mesenchymal stromal cells from young healthy donors and patients with severe chronic coronary artery disease. Scand J Clin Lab Invest. 2011 Jan 11; Authors: Friis T, Haack-Sørensen M, Hansen SK, Hansen L, Bindslev L, Kastrup J Abstract Background: It has been questioned whether bone marrow-derived mesenchymal stromal cells (MSCs) from patients with ischemic heart disease are suitable for use in regenerative stem cell therapy. We compared MSCs from patients with chronic coronary artery disease (CAD) and MSCs from young healthy donors with respect to phenotype, proliferation and endothelial differentiation capacity. Methods: MSCs from 16 young healthy donors and 15 elderly CAD patients were isolated, expanded by ex-vivo cultivation for two cell passages and characterized by flow cytometry, real time PCR and angiogenesis assay. Results: MSCs from healthy donors and CAD patients expressed the same surface markers and had similar proliferation capacity. In both groups VEGF-stimulation significantly increased the expression of the endothelial genes thrombospondin 1, Tie-2 and von Willebrand Factor and induced the capacity to form ring structures on extracellular matrix. Discussion: MSCs from young healthy donors and CAD patients proliferate equally well, express the same surface markers and increase in endothelial gene expression and ring structure formation capacity in the angiogenesis assay upon VEGF-stimulation. MSCs from CAD patients do not seem to be inferior to MSCs from young healthy donors thus indicating that autologous MSCs may be suitable for cell therapy in CAD patients. PMID: 21222501 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Osteogenic potential of rat stromal cells derived from periodontal ligament. J Tissue Eng Regen Med. 2011 Jan 12; Authors: Kato T, Hattori K, Deguchi T, Katsube Y, Matsumoto T, Ohgushi H, Numabe Y Various mesenchymal stromal cells (MSCs) have been applied to regenerative medicine. MSCs derived from periodontal tissue could also be a useful cell source for alveolar bone regeneration. However, only a few attempts of direct comparisons have been made between MSCs from periodontal tissues and those from other somatic tissues. The purpose of this study was to clarify the osteogenic characteristics of mesenchymal stromal cells derived from bone marrow (BMSCs), adipose tissue (ASCs) and periodontal ligament (PDLSCs). BMSCs, ASCs and PDLSCs were isolated from Fisher 344 rats. After 1 week of primary culture, stromal cells were subjected to cell surface analysis and osteogenic differentiation. The cells were subcultured for 2 weeks with and without osteogenic supplements (OS), followed by biochemical and histological analyses. With regard to cell surface antigens, all MSCs were positive for CD29 and CD90 and negative for CD45. With regard to osteogenic differentiation, BMSCs with OS had the highest ALP activity, calcium uptake and osteocalcin content. Without OS, PDLSCs had the highest levels of these bone differentiation markers. RT-PCR analysis and histological analysis showed similar trends. These results indicate that PDLSCs are an ideal candidate for alveolar bone regeneration. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21226080 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Characterization of the laminin gene family and evolution in zebrafish. Dev Dyn. 2011 Jan 11; Authors: Sztal T, Berger S, Currie PD, Hall TE Laminins are essential components of all basement membranes and are fundamental to tissue development and homeostasis. Humans possess at least 16 different heterotrimeric laminin complexes formed through different combinations of alpha, beta, and gamma chains. Individual chains appear to exhibit unique expression patterns, leading to the notion that overlap between expression domains governs the constitution of complexes found within particular tissues. However, the spatial and temporal expression of laminin genes has not been comprehensively analyzed in any vertebrate model to date. Here, we describe the tissue-specific expression patterns of all laminin genes in the zebrafish, throughout embryonic development and into the "post-juvenile" period, which is representative of the adult body form. In addition, we present phylogenetic and microsynteny analyses, which demonstrate that the majority of our zebrafish sequences are orthologous to human laminin genes. Together, these data represent a fundamental resource for the study of vertebrate laminins. Developmental Dynamics, 2011. © 2011 Wiley-Liss, Inc. PMID: 21226064 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Functional mesenchymal stem cell niches in the adult knee joint synovium in vivo. Arthritis Rheum. 2011 Jan 11; Authors: Kurth TB, Dell'accio F, Crouch V, Augello A, Sharpe PT, De Bari C OBJECTIVE:: We previously reported that human synovium contains cells that, after culture-expansion, display properties of mesenchymal stem cells (MSCs). The objective of this study was to identify MSCs in the native synovium in vivo. METHODS:: To identify stem cells in the synovium in vivo, a double nucleoside-analogue cell-labelling scheme was used in a mouse model of joint surface injury. To label slow-cycling cells, mice received IdU for 30 days followed by a 40-day wash-out period. To label cells that proliferate after injury, mice underwent knee surgery to produce an articular cartilage defect and received CldU for 4 days starting at multiple time-points after surgery. Non-operated and sham-operated joints served as controls. Knee joint paraffin sections were analyzed by double and triple immunostaining to detect nucleoside analogues, conventional MSC markers, and chondrocyte-lineage markers. RESULTS:: Long-term retaining, slow-cycling IdU-positive cells were detected in the synovium. At 4 and 8 days after injury, there was marked proliferation of IdU-positive cells, which co-stained for CldU. IdU-positive cells were non-haematopoietic, non-endothelial stromal cells, distinct from pericytes, and stained positive for MSC markers. MSCs were phenotypically heterogeneous and located in topographically distinct niches in the lining layer and the subsynovial tissue. At 12 days after injury, double-nucleoside labelled cells within synovium were embedded in cartilage-specific metachromatic extracellular matrix and co-stained positive for the chondrocyte-lineage markers Sox9 and collagen type 2. CONCLUSION:: Our findings provide first evidence of existence of resident MSCs in the knee joint synovium, which undergo proliferation and chondrogenic differentiation following injury in vivo. PMID: 21226037 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Proteomics of human embryonic stem cells. Proteomics. 2010 Dec 15; Authors: Hughes CS, Nuhn AA, Postovit LM, Lajoie GA Human embryonic stem cells (hESCs) offer exciting potential in regenerative medicine for the treatment of a host of diseases including cancer, Alzheimer's and Parkinson's disease. They also provide insight into human development and disease and can be used as models for drug discovery and toxicity analyses. The key properties of hESCs that make them so promising for medical use are that they have the ability to self-renew indefinitely in culture and they are pluripotent, which means that they can differentiate into any of more than 200 human cell types. Since proteins are the effectors of cellular processes, it is important to investigate hESC expression at the protein level as well as at the transcript level. In addition, post-translational modifications, such as phosphorylation, may influence the activity of pivotal proteins in hESCs, and this information can only be determined by studying the proteome. In this review, we summarize the results obtained from several proteomics analyses of hESCs that have been reported in the last few years. PMID: 21225999 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatology. 2010 Nov 12; Authors: Baptista PM, Siddiqui MM, Lozier G, Rodriguez SR, Atala A, Soker S A major roadblock to successful organ bioengineering is the need for a functional vascular network within the engineered tissue. Here, we describe the fabrication of three-dimensional, naturally derived scaffolds with an intact vascular tree. Livers from different species were perfused with detergent to selectively remove the cellular components of the tissue while preserving the extracellular matrix components and the intact vascular network. The decellularized vascular network was able to withstand fluid flow that entered through a central inlet vessel, branched into an extensive capillary bed, and coalesced into a single outlet vessel. The vascular network was used to reseed the scaffolds with human fetal liver and endothelial cells. These cells engrafted in their putative native locations within the decellularized organ and displayed typical endothelial, hepatic, and biliary epithelial markers, thus creating a liver-like tissue in vitro. Conclusion: These results represent a significant advancement in the bioengineering of whole organs. This technology may provide the necessary tools to produce the first fully functional bioengineered livers for organ transplantation and drug discovery. (HEPATOLOGY 2011;). PMID: 21225647 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Possible mechanisms of retinal function recovery with the use of cell therapy with bone marrow-derived stem cells. Arq Bras Oftalmol. 2010 Oct;73(5):474-9 Authors: Siqueira RC, Voltarelli JC, Messias AM, Jorge R Bone marrow has been proposed as a potential source of stem cells for regenerative medicine. In the eye, degeneration of neural cells in the retina is a hallmark of such widespread ocular diseases as age-related macular degeneration (AMD) and retinitis pigmentosa. Bone marrow is an ideal tissue for studying stem cells mainly because of its accessibility. Furthermore, there are a number of well-defined mouse models and cell surface markers that allow effective study of hematopoiesis in healthy and injured mice. Because of these characteristics and the experience of bone marrow transplantation in the treatment of hematological disease such as leukemia, bone marrow-derived stem cells have also become a major tool in regenerative medicine. Those cells may be able to restore the retina function through different mechanisms: A) cellular differentiation, B) paracrine effect, and C) retinal pigment epithelium repair. In this review, we described these possible mechanisms of recovery of retinal function with the use of cell therapy with bone marrow-derived stem cells. PMID: 21225138 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Synthesis of Janus type nucleoside analogues and their preliminary bioactivity. Org Biomol Chem. 2011 Jan 12; Authors: Yang HZ, Pan MY, Jiang DW, He Y Novel Janus type nucleoside analogues 1a and 1b were synthesized in seven steps from 2-amino-4,6-dihydroxypyrimidine and 4,6-dihydroxypyrimidine. The base moiety of 1a has one face with a Watson-Crick donor-donor-acceptor (DDA) H-bond array of guanine and the other face with an acceptor-acceptor-donor (AAD) array of cytosine, which might lead to its base pairing with either cytosine or guanine due to the rotating of the glycosyl bond. This property may enable Janus type nucleoside analogues to act as an antiviral compound in a similar way to ribavirin. Both 1a and 1b were screened by a vitro HBV DNA replication inhibition test and indeed 1a showed a great potential with IC(50) = 10 μM and SI = 78.9 for antiviral drug development. PMID: 21225056 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Genetic influences on exercise-induced adult hippocampal neurogenesis across 12 divergent mouse strains. Genes Brain Behav. 2011 Jan 12; Authors: Clark PJ, Kohman RA, Miller DS, Bhattacharya TK, Brzezinska WJ, Rhodes JS New neurons are continuously born in the hippocampus of several mammalian species throughout adulthood. Adult neurogenesis represents a natural model for understanding how to grow and incorporate new nerve cells into preexisting circuits in the brain. Finding molecules or biological pathways that increase neurogenesis has broad potential for regenerative medicine. One strategy is to identify mouse strains that display large vs. small increases in neurogenesis in response to wheel running so that the strains can be contrasted to find common genes or biological pathways associated with enhanced neuron formation. Therefore, mice from 12 different isogenic strains were housed with or without running wheels for 43 days to measure the genetic regulation of exercise-induced neurogenesis. During the first 10 days mice received daily injections of 5-bromo-2'-deoxyuridine (BrdU) to label dividing cells. Neurogenesis was measured as the total number of BrdU cells co-expressing NeuN mature neuronal marker in the hippocampal granule cell layer by immunohistochemistry. Exercise increased neurogenesis in all strains, but the magnitude significantly depended on genotype. Strain means for distance run on wheels, but not distance traveled in cages without wheels, were significantly correlated with strain mean level of neurogenesis. Furthermore, certain strains displayed greater neurogenesis than others for a fixed level of running. Strain means for neurogenesis under sedentary conditions were not correlated with neurogenesis under runner conditions suggesting that different genes influence baseline vs. exercise-induced neurogenesis. Genetic contributions to exercise-induced hippocampal neurogenesis suggest that it may be possible to identify genes and pathways associated with enhanced neuroplastic responses to exercise. PMID: 21223504 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effect of the SK/IK channel modulator 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591) on contractile force in rat, pig and human detrusor smooth muscle. BJU Int. 2011 Jan 11; Authors: Nielsen JS, Rode F, Rahbek M, Andersson KE, Rønn LC, Bouchelouche K, Nordling J, Bouchelouche P OBJECTIVE: • To investigate the importance of small (SK)- and intermediate (IK)-conductance Ca2(+) -activated K(+) channels on bladder function, by studying the effects of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a new modulator of SK/IK channels, on contractions induced by electrical field stimulation (EFS) and carbachol in rat, pig and human detrusor. PATIENTS AND METHODS: • Detrusor biopsies were obtained from rats, pigs and male patients undergoing cystectomy because of bladder cancer. • Force was recorded using myographs. • Intracellular free Ca(2+) was measured in myocytes using microfluorimetry. RESULTS: • In rat bladder rings subjected to EFS, cumulative addition of NS4591 (0.1-30 µM) decreased force by 82 ± 2.9% (n = 6).This effect was reduced by 64 ± 5.2% in the presence of 0.3 µM apamin, a specific inhibitor of SK channels. Apamin increased the force evoked by EFS significantly: force was increased by 14.2 ± 3.4% (n = 5) and 10.1 ± 2.6% (n = 7) in pig and human detrusor strips, respectively (P = 0.04 and P = 0.02). • The cumulative addition of NS4591 (0.3-30 µM) significantly reduced the amplitude of carbachol-induced rhythmic oscillations by 62.0 ± 12.0% (n = 12) and the minimum force between oscillations by 30 ± 5% (n = 9) in pig detrusor strips (P < 0.005). In the presence of 10 µM NS4591, carbachol (1 µM) induced rhythmic contractions with an amplitude and normalized mean power frequency (nmeanPF) of 8.4 ± 5.1% and 0.11 ± 0.06 mN root mean square (rms) Hz (n = 12), respectively, vs. 21 ± 3.4% and 0.17 ± 0.04 mN rms Hz in control strips (n = 13). Apamin induced 6- and 11-fold increases in amplitude and nmeanPF vs. 1.3- and 2-fold increases in control strips. • In human detrusor strips (n = 15), the cumulative addition of NS4591 (1-30 µM) significantly reduced the amplitude by 69 ± 11%, the nmeanPF by 78 ± 6% and the minimum force between carbachol-induced oscillations by 59 ± 5% (P < 0.008). The addition of apamin (0.3 µM) before application of 1 µM carbachol abolished the effects of NS4591 on amplitude and partially abolished its effect on nmeanPF by 41 ± 7%, vs. a 78 ± 6% reduction in the absence of apamin (n = 8). • In spontaneously active detrusor preparations, NS4591 reduced or abolished contractions. • Furthermore, NS4591 (10 µM) decreased the carbachol-induced increase in the fura-2 ratio by 43 ± 3% compared with control (n = 12) (P < 0.03). CONCLUSIONS: • The SK/IK channel modulator NS4591 inhibits EFS- and carbachol-induced contractions in rat, pig and human detrusor muscle. • NS4591 may have therapeutic potential for treatment of detrusor overactivity. PMID: 21223472 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Salivary gland progenitor cell biology provides a rationale for therapeutic salivary gland regeneration. Oral Dis. 2011 Jan 11; Authors: Lombaert I, Knox S, Hoffman M Oral Diseases (2011) An irreversible loss of salivary gland function often occurs in humans after removal of salivary tumors, after therapeutic radiation of head and neck tumors, as a result of Sjögren's syndrome and in genetic syndromes affecting gland development. The permanent loss of gland function impairs the oral health of these patients and broadly affects their quality of life. The regeneration of functional salivary gland tissue is thus an important therapeutic goal for the field of regenerative medicine and will likely involve stem/progenitor cell biology and/or tissue engineering approaches. Recent reports demonstrate how both innervation of the salivary gland epithelium and certain growth factors influence progenitor cell growth during mouse salivary gland development. These advances in our understanding suggest that developmental mechanisms of mouse salivary gland development may provide a paradigm for postnatal regeneration of both mice and human salivary glands. Herein, we will discuss the developmental mechanisms that influence progenitor cell biology and the implications for salivary gland regeneration. PMID: 21223454 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal Stromal Cells: Past, Present, and Future. Vet Surg. 2011 Jan 11; Authors: Spencer ND, Gimble JM, Lopez MJ Adult mesenchymal stromal cells are plastic-adherent cells that are self-renewing and have the capacity to differentiate into various tissue specific lineages. Stromal cells were initially discovered over 100 years ago and substantial insight into stromal cell identification, isolation, characterization, and differentiation has been made, including efforts to elucidate the factors involved in stromal cell differentiation. Stromal cells have immune privilege and thus are attractive candidates for tissue engineering and regenerative medicine applications. Positive results from a number of recent investigations support the use of adult mesenchymal stromal cells for clinical application. This review article provides a brief overview of past, present, and future stromal cell technology. PMID: 21223314 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Where are the systematic reviews in transfusion medicine? A study of the transfusion evidence base. Transfus Med Rev. 2010 Oct;24(4):286-94 Authors: Dorée C, Stanworth S, Brunskill SJ, Hopewell S, Hyde CJ, Murphy MF Transfusion medicine has become a large and complex specialty. Although there are now systematic reviews covering many aspects of transfusion, these span a large number of clinical areas and are published across more than a hundred different medical journals, making it difficult for transfusion medicine practitioners and researchers to keep abreast of the current high-level evidence. In response to this problem, NHS Blood and Transplant's Systematic Review Initiative (SRI) has produced a comprehensive overview of systematic reviews in transfusion medicine. A systematic search (to December 2009) and screening procedure were followed by the appraisal of systematic reviews according to predefined inclusion criteria. The 340 eligible systematic reviews were mapped to 10 transfusion intervention groups and 14 topic groups within clinical medicine. Trends in the systematic review literature were examined and gaps in the literature described. The spread of systematic reviews across clinical areas was found to be very uneven, with some areas underreviewed and others with multiple systematic reviews on the same topic, making the identification of the best evidence for current transfusion practice a continuing challenge. References and links to all systematic reviews included in this overview can be freely accessed via the SRI's new online database, the Transfusion Evidence Library (www.transfusionguidelines.org). PMID: 20851331 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Clinical trial opportunities in Transfusion Medicine: proceedings of a National Heart, Lung, and Blood Institute State-of-the-Science Symposium. Transfus Med Rev. 2010 Oct;24(4):259-85 Authors: Blajchman MA, Glynn SA, Josephson CD, Kleinman SH, The use of blood products to support patients undergoing the large variety of medical and surgical interventions requiring such support has continued to escalate very significantly over time. Relevantly, significant practice variation in the use of blood products exists among practitioners and institutions, largely because of the lack of robust clinical trial data, in many instances, which are critical for providing practitioners with evidence-based guidelines for appropriate blood product utilization. Recognizing this gap, the National Heart, Lung, and Blood Institute recently established a State-of-the-Science Symposium to help define areas of clinical trial research that would enhance the opportunity for developing appropriate practice guidelines for both Transfusion Medicine and Hemostasis/Thrombosis. Such a Symposium was held in September 2009 to identify important clinical trial research issues in these 2 subject areas of endeavor. The aims of this Symposium were to specifically identify phase 2 and 3 clinical trials that, if conducted over the next 5 to 10 years, could impact the treatment of patients with hemostatic and other disorders as well as to optimize the use of blood products in patients who need such interventions. This article reports on the deliberations that were held relating to the various clinical trial concepts developed by 7 Transfusion Medicine subcommittees. This Symposium generated a rich assortment of clinical trial proposals that will undergo further refinement before final implementation into pilot or full randomized clinical trials. The various proposals identified many opportunities for clinical trial research and most importantly underscored the ongoing need for well-developed evidence-based clinical trial research in the field of Transfusion Medicine. PMID: 20851330 [PubMed - indexed for MEDLINE] | | | | | | | | | |  | |  | |  |
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