|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Mucopolysaccharidosis Type IVA (Morquio A Disease): Clinical Review and Current Treatment. Curr Pharm Biotechnol. 2011 Apr 20; Authors: Tomatsua S, Montañoa AM, Oikawaa H, Smithb M, Barrerac L, Chinend Y, Thackere MM, Mackenziee WG, Suzukif Y, Oriif T Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio A, is a rare, autosomal recessive disorder caused by a deficiency of the lysosomal enzyme N-acetylgalatosamine-6-sulfate-sulfatase (GALNS), which catalyzes a step in the catabolism of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate (C6S). It leads to accumulation of the KS and C6S, mainly in bone and cornea, causing a systemic skeletal chondrodysplasia. MPS IVA has a variable age of onset and variable rate of progression. Common presenting features include elevation of urinary and blood KS, marked short stature, hypoplasia of the odontoid process, pectus carinatum, kyphoscoliosis, genu valgum, laxity of joints and corneal clouding; however there is no central nervous system impairment. Generally, MPS IVA patients with a severe form do not survive beyond the third decade of life whereas those patients with an attenuated form may survive over 70 years. There has been no effective therapy for MPS IVA, and care has been palliative. Enzyme replacement therapy (ERT) and hematopoietic stem cell therapy (HSCT) have emerged as a treatment for mucopolysaccharidoses disorders, including Morquio A disease. This review provides an overview of the clinical manifestations, diagnosis and symptomatic management of patients with MPS IVA and describes potential perspectives of ERT and HSCT. The issue of treating very young patients is also discussed. PMID: 21506915 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effects of extracellular matrices derived from different cell sources on chondrocyte functions. Biotechnol Prog. 2011 Mar 22; Authors: Hoshiba T, Lu H, Yamada T, Kawazoe N, Tateishi T, Chen G Cell-derived extracellular matrices (ECMs) are a key factor in regulating cell functions in tissue engineering and regenerative medicine. The fact that cells are surrounded by their specific ECM in vivo elicits the need to elucidate the effects of ECM derived from different cell sources on cell functions. Here, three types of ECM were prepared by decellularizing cultured chondrocytes, fibroblasts, and mesenchymal stem cells (MSC) and used for chondrocyte culture to compare their effects on chondrocyte adhesion, proliferation, and differentiation. Chondrocyte adhesion to the chondrocyte-derived ECM was greater than those to the fibroblast- and MSC-derived ECM. Chondrocyte proliferation on the chondrocyte-derived ECM was lower than those on the fibroblast- and MSC-derived ECM. The ECM showed no evident effect on chondrocyte differentiation. The effects of ECM on cell functions depended on the cell source used to prepare the ECM. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011. PMID: 21509950 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Towards responsible cord blood banking models. Cell Prolif. 2011 Apr;44 Suppl 1:30-4 Authors: Rebulla P, Lecchi L On 31 May 2010, 14 072 567 bone marrow/apheresis donors registered in 44 countries and 426 501 cord blood units banked in 26 countries for public use were available to treat candidates to haemopoietic stem cell transplant lacking a family related compatible donor. Despite these impressive numbers, additional efforts are required to ensure that all patients, including those from ethnic minorities, can promptly find a suitable donor. Governments, clinicians, scientists, patients and stakeholders should share the responsibility to develop haemopoietic stem cell donation and cord blood banking models able to fully match all patient needs. In this regard, current scientific evidence and prevalent opinions among expert clinicians support solidaristic cord blood donation for public use against the alternative option of commercial autologous cord blood storage. PMID: 21481040 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Quantitative Comparison of Erythropoietin Receptor Levels in the Epithelial versus Endothelial Fractions of Primary Breast Tumors. Anticancer Res. 2011 Apr;31(4):1189-95 Authors: Miller CP, Urban N, Blau CA Erythropoietin (EPO) was shown to reduce tumor survival in recent trials, however, its mechanisms of action are unclear. Efforts to measure tumor EPO receptor (EPOR) are limited by the promiscuity of EPOR antibodies, and concerns as to whether EPOR mRNA measurements are confounded by heterogeneity of tumor vasculature, a known EPOR source. PMID: 21508364 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Enhancing remyelination in disease--can we wrap it up? Brain. 2011 Apr 19; Authors: Kotter MR, Stadelmann C, Hartung HP Demyelinating disorders of the central nervous system are among the most crippling neurological diseases affecting patients at various stages of life. In the most prominent demyelinating disease, multiple sclerosis, the regeneration of myelin sheaths often fails due to a default of the resident stem/precursor cells (oligodendrocyte precursor cells) to differentiate into mature myelin forming cells. Significant advances have been made in our understanding of the molecular and cellular processes involved in remyelination. Furthermore, important insight has been gained from studies investigating the interaction of stem/precursor cells with the distinct environment of demyelinating lesions. These suggest that successful regeneration depends on a signalling environment conducive to remyelination, which is provided in the context of acute inflammation. However, multiple sclerosis lesions also contain factors that inhibit the differentiation of oligodendrocyte precursor cells into myelinating oligodendrocytes. The pattern by which remyelination inducers and inhibitors are expressed in multiple sclerosis lesions may determine a window of opportunity during which oligodendrocyte precursor cells can successfully differentiate. As the first molecules aiming at promoting remyelination are about to enter clinical trials, this review critically evaluates recent advances in our understanding of the biology of oligodendrocyte precursor cells and of the stage-dependent molecular pathology of multiple sclerosis lesions relevant to the regeneration of myelin sheaths. We propose a model that may help to provide cues for how remyelination can be therapeutically enhanced in clinical disease. PMID: 21507994 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Human induced pluripotent stem cells derived under feeder-free conditions display unique cell cycle and DNA replication gene profiles. Stem Cells Dev. 2011 Apr 20; Authors: Chung HC, Lin RC, Logan GJ, Alexander IE, Sachdev P, Sidhu KS Use of animal feeder layers and serum containing media in the derivation and propagation of induced pluripotent stem cells (iPSCs) can hinder clinical translation, because of the presence of xeno-material/pathogens. A defined and standardized system would be ideal for generating a homogenous population of iPSCs, which closely resembles human embryonic stem cells (hESCs). We report here a novel and extensive comparison between our in-house produced iPSCs and hESCs under 'feeder' and 'feeder-free' conditions, using transcriptomic genome-wide microarray analysis. We generated a list of pluripotency-associated and bivalent domain-containing genes by meta-analysis to measure qualitatively the degree of reprogramming in feeder-free derived, in which both profiles displayed similar levels of gene expression as in hESCs. Gene ontology analysis showed that feeder-free iPSCs have enriched terms belonging to DNA repair/replication and cell cycle, which are signature to pluripotent cells. Transcriptomic data combined with directed differentiation assays, indicated that variability among iPSC lines is minimized when using a feeder-free cultural system, which may serve as a platform for further developing regenerative medicine compliant human iPSCs. PMID: 21506733 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The umbilical cord: a rich and ethical stem cell source to advance regenerative medicine. Cell Prolif. 2011 Apr;44 Suppl 1:60-9 Authors: Forraz N, McGuckin CP Science and medicine place a lot of hope in the development of stem cell research and regenerative medicine. This review will define the concept of regenerative medicine and focus on an abundant stem cell source - neonatal tissues such as the umbilical cord. Umbilical cord blood has been used clinically for over 20 years as a cell source for haematopoietic stem cell transplantation. Beyond this, cord blood and umbilical cord-derived stem cells have demonstrated potential for pluripotent lineage differentiation (liver, pancreatic, neural tissues and more) in vitro and in vivo. This promising research has opened up a new era for utilization of neonatal stem cells, now used beyond haematology in clinical trials for autoimmune disorders, cerebral palsy or type I diabetes. PMID: 21481046 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | From hepatocytes to stem and progenitor cells for liver regenerative medicine: advances and clinical perspectives. Cell Prolif. 2011 Apr;44 Suppl 1:39-43 Authors: Sokal EM The parenchymal liver cell is a unique fully functional metabolic unit that can be used for liver regenerative medicine to restore function of the diseased organ; the aim of the procedure is to prevent progression of end-stage disease. The alternative, orthotopic liver transplantation, is highly intrusive, irreversible and limited by general organ shortage. Mature liver cell - hepatocyte - transplantation has been shown to have short- to medium-term efficacy for correction of miscellaneous inborn errors of metabolism. However, although proof of concept has been established, the procedure has not yet achieved full success, due to limited durability of functional benefit. Hepatocyte procurement is also restricted by organ shortage, and their storage is difficult due to poor tolerance of cryopreservation. Alternative cell sources are therefore needed for development and wider accessibility of cell-based liver regenerative medicine. Besides safety, the main challenge for these alternative cells is to acquire similar levels of functionality once implanted into the target organ. In this respect, liver derived progenitor cells may have some advantages over stem cells derived from other tissues. PMID: 21481042 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Exciting times for our field and the Journal. Exp Hematol. 2011 Mar;39(3):271 Authors: Humphries RK PMID: 21277347 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Biological performance of a novel biodegradable polyamidoamine hydrogel as guide for peripheral nerve regeneration. J Biomed Mater Res A. 2011 Apr 20; Authors: Magnaghi V, Conte V, Procacci P, Pivato G, Cortese P, Cavalli E, Pajardi G, Ranucci E, Fenili F, Manfredi A, Ferruti P Polyamidoamines (PAAs) are a well-known family of synthetic biocompatible and biodegradable polymers, which can be prepared as soft hydrogels characterized by low interfacial tension and tunable elasticity. For the first time we report here on the in vivo performance of a PAA hydrogel implant as scaffold for tissue engineering. In particular, an amphoteric agmatine-deriving PAA hydrogel shaped as small tubing was obtained by radical polymerization of a soluble functional oligomeric precursor and used as conduit for nerve regeneration in a rat sciatic nerve cut model. The animals were analyzed at 30, 90, and 180 days post-surgery. PAA tubing proved to facilitate nerve regeneration. Good surgical outcomes were achieved with no signs of inflammation or neuroma. Moreover, nerve regeneration was morphologically sound and the quality of functional recovery satisfactory. In conclusion, PAA hydrogel scaffolds may represent a novel and promising material for peripheral nerve regeneration. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011. PMID: 21509933 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Controlled growth and differentiation of MSCs on grooved films assembled from monodisperse biological nanofibers with genetically tunable surface chemistries. Biomaterials. 2011 Apr 18; Authors: Zhu H, Cao B, Zhen Z, Laxmi AA, Li D, Liu S, Mao C The search for a cell-supporting scaffold with controlled topography and surface chemistry is a constant topic within tissue engineering. Here we have employed M13 phages, which are genetically modifiable biological nanofibers (∼880 nm long and ∼6.6 nm wide) non-toxic to human beings, to form films for supporting the growth of mesencymal stem cells (MSCs). Films were built from nearly parallel phage bundles separated by grooves. The bundles can guide the elongation and alignment of MSCs along themselves. Phage with peptides displayed on the surface exhibited different control over the fine morphologies and differentiation of the MSCs. When an osteogenic peptide was displayed on the surface of phage, the proliferation and differentiation of MSCs into osteoblasts were significantly accelerated. The use of the grooved phage films allows us to control the proliferation and differentiation of MSCs by simply controlling the concentrations of phages as well as the peptides displayed on the surface of the phages. This work will advance our understanding on the interaction between stem cells and proteins. PMID: 21507480 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | In Vitro and In Vivo Evaluation of Adenovirus Combined Silk Fibroin Scaffolds for Bone Morphogenetic Protein-7 Gene Delivery. Tissue Eng Part C Methods. 2011 Apr 20; Authors: Zhang Y, Fan W, Nothdurft L, Wu C, Zhou Y, Crawford R, Xiao Y Introduction and Aims: For a scaffold material to be considered effective and efficient for tissue engineering, it should be biocompatible and bioinductive. Silk fiber is a natural biocompatible material suitable for scaffold fabrication; however, silk is tissue conductive and lacks tissue-inductive properties. One proposed method to make the scaffold tissue inductive is to introduce plasmids or viruses encoding a specific growth factor into the scaffold. In this study, we constructed adenoviruses encoding bone morphogenetic protein-7 (BMP-7) and incorporated these into silk scaffolds. The osteoinductive and new bone formation properties of these constructs were assessed in vivo in a critical-sized skull defect animal model. Materials and Methods: Silk fibroin scaffolds containing adenovirus particles coding BMP-7 were prepared. The release of the adenovirus particles from the scaffolds was quantified by tissue-culture infective dose (TCID50), and the bioactivity of the released viruses was evaluated on human bone marrow mesenchymal stromal cells (BMSCs). To demonstrate the in vivo bone forming ability of the virus-carrying silk fibroin scaffold, the scaffold constructs were implanted into calvarial defects in SCID mice. Results: In vitro studies demonstrated that the virus-carrying silk fibroin scaffold released virus particles over a 3-week period while preserving their bioactivity. In vivo test of the scaffold constructs in critical-sized skull defect areas revealed that silk scaffolds were capable of delivering the adenovirus encoding BMP-7, resulting in significantly enhanced new bone formation. Conclusions: Silk scaffolds carrying BMP-7 encoding adenoviruses can effectively transfect cells and enhance both in vitro and in vivo osteogenesis. The findings of this study indicate that silk fibroin is a promising biomaterial for gene delivery to repair critical-sized bone defects. PMID: 21506685 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Histological evaluation and biomechanical characterisation of an acellular porcine cornea scaffold. Br J Ophthalmol. 2011 Mar;95(3):410-4 Authors: Du L, Wu X, Pang K, Yang Y To optimise a protocol to produce an acellular porcine cornea scaffold and investigate its mechanical integrity and biocompatibility. PMID: 20956275 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Covalent Growth Factor Immobilization Strategies for Tissue Repair and Regeneration. Macromol Biosci. 2011 Apr 20; Authors: Masters KS Growth factors play a critical role in regulating processes involved in cellular differentiation and tissue regeneration, and are therefore considered essential elements in many tissue engineering strategies. The covalent immobilization of growth factors to biomaterial matrices addresses many of the challenges associated with delivering freely-diffusible growth factors and has thus emerged as a promising method of achieving localized and sustained growth factor delivery. This Feature Article discusses methods that have been used to immobilize growth factors to substrates, followed by an overview of several tissue repair and regeneration applications in which immobilized growth factors have been used. PMID: 21509937 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Engineered heart tissue enables study of residual undifferentiated embryonic stem cell activity in a cardiac environment. Biotechnol Bioeng. 2011 Mar;108(3):704-19 Authors: Dengler J, Song H, Thavandiran N, Massé S, Wood GA, Nanthakumar K, Zandstra PW, Radisic M Embryonic stem cell (ESC) derivatives are a promising cell source for cardiac cell therapy. Mechanistic studies upon cell injection in conventional animal models are limited by inefficient delivery and poor cell survival. As an alternative, we have used an engineered heart tissue (EHT) based on neonatal rat cardiomyocytes (CMs) cultivated with electrical field stimulation as an in vitro model to study cell injection. We injected (0.001, 0.01, and 0.1 million) and tracked (by qPCR and histology) undifferentiated yellow-fluorescent protein transgenic mouse ESCs and Flk1 + /PDGFRα+ cardiac progenitor (CPs) cells, to investigate the effect of the cardiac environment on cell differentiation, as well as to test whether our in vitro model system could recapitulate the formation of teratoma-like structures commonly observed upon in vivo ESC injection. By 8 days post-injection, ESCs were spatially segregated from the cardiac cell population; however, ESC injection increased survival of CMs. The presence of ESCs blocked electrical conduction through the tissue, resulting in a 46% increase in the excitation threshold. Expression of mouse cardiac troponin I, was markedly increased in CP injected constructs compared to ESC injected constructs at all time points and cell doses tested. As early as 2 weeks, epithelial and ganglion-like structures were observed in ESC injected constructs. By 4 weeks of ESC injection, teratoma-like structures containing neural, epithelial, and connective tissue were observed in the constructs. Non-cardiac structures were observed in the CP injected constructs only after extended culture (4 weeks) and only at high cell doses, suggesting that these cells require further enrichment or differentiation prior to transplantation. Our data indicate that the cardiac environment of host tissue and electrical field stimulation did not preferentially guide the differentiation of ESCs towards the cardiac lineage. In the same environment, injection of CP resulted in a more robust cardiac differentiation than injection of ESC. Our data demonstrate that the model-system developed herein can be used to study the functional effects of candidate stem cells on the host myocardium, as well as to measure the residual activity of undifferentiated cells present in the mixture. PMID: 21246514 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Composite scaffold provides a cell delivery platform for cardiovascular repair. Proc Natl Acad Sci U S A. 2011 Apr 20; Authors: Godier-Furnémont AF, Martens TP, Koeckert MS, Wan L, Parks J, Arai K, Zhang G, Hudson B, Homma S, Vunjak-Novakovic G Control over cell engraftment, survival, and function remains critical for heart repair. We have established a tissue engineering platform for the delivery of human mesenchymal progenitor cells (MPCs) by a fully biological composite scaffold. Specifically, we developed a method for complete decellularization of human myocardium that leaves intact most elements of the extracellular matrix, as well as the underlying mechanical properties. A cell-matrix composite was constructed by applying fibrin hydrogel with suspended cells onto decellularized sheets of human myocardium. We then implanted this composite onto the infarct bed in a nude rat model of cardiac infarction. We next characterized the myogenic and vasculogenic potential of immunoselected human MPCs and demonstrated that in vitro conditioning with a low concentration of TGF-β promoted an arteriogenic profile of gene expression. When implanted by composite scaffold, preconditioned MPCs greatly enhanced vascular network formation in the infarct bed by mechanisms involving the secretion of paracrine factors, such as SDF-1, and the migration of MPCs into ischemic myocardium, but not normal myocardium. Echocardiography demonstrated the recovery of baseline levels of left ventricular systolic dimensions and contractility when MPCs were delivered via composite scaffold. This adaptable platform could be readily extended to the delivery of other reparative cells of interest and used in quantitative studies of heart repair. PMID: 21508321 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Amide-linkage formed between ammonia (NH(3) ) plasma treated Poly (D, L-lactide acid) scaffolds and bio-peptides: Enhancement of cell adhesion and osteogenic differentiation in vitro. Biopolymers. 2011 Apr 20; Authors: Xu Z, Li T, Zhong Z, Zha D, Wu S, Liu F, Xiao W, Jiang X, Zhang X, Chen J The surface characteristics of scaffolds for bone tissue engineering must support cell adhesion, migration, proliferation and osteogenic differentiation. In the study, Poly (D, L-lactide acid) (PDLLA) scaffolds were modified by combing ammonia (NH(3) ) plasma pre-treatment with Gly-Arg-Gly-Asp-Ser (GRGDS)-peptides coupling technologies. The X-ray photoelectron spectroscopy (XPS) survey spectra showed the peak of N 1s at the surface of NH(3) plasma pre-treated PDLLA, which was further raised after GRGDS conjugation. Furthermore, N 1s and C 1s in the high-resolution XPS spectra revealed the presence of -C=N (imine), -C-NH- (amine) and -C=O-NH- (amide) groups. The GRGDS conjugation increased amide groups and decreased amine groups in the plasma-treated PDLLA. Confocal microscope and high performance liquid chromatography verified the anchored peptides after the conjugation process. Bone marrow mesenchymal stem cells were co-cultured with scaffolds. Fluorescent microscope and scanning electron microscope photographs revealed the best cell adhesion in NH(3) plasma pre-treated and GRGDS conjugated scaffolds, and the least attachment in un-modified scaffolds. Real-time PCR demonstrated that expression of osteogenesis-related genes, such as osteocalcin, alkaline phosphatase, type I collagen, bone morphogenetic protein-2 and osteopontin, was up-regulated in the single NH(3) plasma treated and NH(3) plasma pre-treated scaffolds following GRGDS conjugation. The results show that NH(3) plasma treatment promotes the conjugation of GRGDS peptides to the PDLLA scaffolds via the formation of amide linkage, and combination of NH(3) plasma treatment and peptides conjugation may enhance the cell adhesion and osteogenic differentiation in the PDLLA scaffolds. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2011. PMID: 21509742 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bioartificial oesophagus in the era of tissue engineering. J Pediatr Gastroenterol Nutr. 2011 May;52 Suppl 1:S16-7 Authors: Poghosyan T, Gaujoux S, Sfeir R, Larghero J, Cattan P PMID: 21499036 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Effects of extracellular matrices derived from different cell sources on chondrocyte functions. Biotechnol Prog. 2011 Mar 22; Authors: Hoshiba T, Lu H, Yamada T, Kawazoe N, Tateishi T, Chen G Cell-derived extracellular matrices (ECMs) are a key factor in regulating cell functions in tissue engineering and regenerative medicine. The fact that cells are surrounded by their specific ECM in vivo elicits the need to elucidate the effects of ECM derived from different cell sources on cell functions. Here, three types of ECM were prepared by decellularizing cultured chondrocytes, fibroblasts, and mesenchymal stem cells (MSC) and used for chondrocyte culture to compare their effects on chondrocyte adhesion, proliferation, and differentiation. Chondrocyte adhesion to the chondrocyte-derived ECM was greater than those to the fibroblast- and MSC-derived ECM. Chondrocyte proliferation on the chondrocyte-derived ECM was lower than those on the fibroblast- and MSC-derived ECM. The ECM showed no evident effect on chondrocyte differentiation. The effects of ECM on cell functions depended on the cell source used to prepare the ECM. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011. PMID: 21509950 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Cell-traction mediated configuration of the cell/extracellular-matrix interface plays a key role in stem cell fate]. Med Sci (Paris). 2011 Jan;27(1):19-21 Authors: Bencherif SA, Guillemot F, Huebsch N, Edwards DA, Mooney DJ PMID: 21299954 [PubMed - indexed for MEDLINE] | | | | | | | | | |  | |  | |  |
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