Current Issue : January - March Volume : 2018 Issue Number : 1 Articles : 5 Articles
Background: Human adult stem cells hold the potential for the cure of numerous conditions and degenerative\ndiseases. They possess major advantages over pluripotent stem cells as they can be derived from donors at any\nage, and therefore pose no ethical concerns or risk of teratoma tumor formation in vivo. Furthermore, they have a\nnatural ability to differentiate and secrete factors that promote tissue healing without genetic manipulation.\nHowever, at present, clinical applications of adult stem cells are limited by a shortage of a reliable, standardized,\nand easily accessible tissue source which does not rely on specimens discarded from unrelated surgical procedures.\nMethod: Human tonsil-derived mesenchymal progenitor cells (MPCs) were isolated from a small sample of tonsillar\ntissue (average 0.88 cm3). Our novel procedure poses a minimal mechanical and enzymatic insult to the tissue, and\ntherefore leads to high cell viability and yield. We characterized these MPCs and demonstrated robust multipotency\nin vitro. We further show that these cells can be propagated and maintained in xeno-free conditions.\nResults: We have generated tonsillar biopsy-derived MPC (T-MPC) lines from multiple donors across a spectrum of age,\nsex, and race, and successfully expanded them in culture. We characterized them by cell surface markers, as well as in\nvitro expansion and differentiation potential. Our procedure provides a robust yield of tonsillar biopsy-derived T-MPCs.\nConclusions: Millions of MPCs can be harvested from a sample smaller than 1 g, which can be collected from a fully\nawake donor in an outpatient setting without the need for general anesthesia or hospitalization. Our study identifies\ntonsillar biopsy as an abundant source of adult MPCs for regenerative medicine....
Insulin-like growth factor 1 (IGF1) and neuregulin-1�² (NRG1) play important roles during cardiac development both individually\nand synergistically. In this study, we analyze how 3D cardiac tissue engineered from human embryonic stem cell- (hESC-) derived\ncardiomyocytes and 2D-plated hESC-cardiomyocytes respond to developmentally relevant growth factors both to stimulate\nmaturity and to characterize the therapeutic potential of IGF1 and NRG1. When administered to engineered cardiac tissues, a\nsignificant decrease in active force production of ~65% was measured in all treatment groups, likely due to changes in cellular\nphysiology. Developmentally related processes were identified in engineered tissues as IGF1 increased hESC-cardiomyocyte\nproliferation 3-fold over untreated controls and NRG1 stimulated oxidative phosphorylation and promoted a positive forcefrequency\nrelationship in tissues up to 3 Hz. hESC-cardiomyocyte area increased significantly with NRG1 and IGF1+NRG1\ntreatment in 2D culture and gene expression data suggested increased cardiac contractile components in engineered tissues,\nindicating the need for functional analysis in a 3D platform to accurately characterize engineered cardiac tissue response to\nbiochemical stimulation. This study demonstrates the therapeutic potential of IGF1 for boosting proliferation and NRG1 for\npromoting metabolic and contractile maturation in engineered human cardiac tissue....
The therapeutic effect of induced pluripotent stem cells (iPSs) on the progression of chronic kidney disease (CKD) has not yet been\ndemonstrated. In this study, we sought to assess whether treatment with iPSs retards progression of CKD when compared with\nbone marrow mesenchymal stem cells (BMSCs). Untreated 5/6 nephrectomized rats were compared with CKD animals\nreceiving BMSCs or iPSs. Renal function, histology, immunohistochemistry, and gene expression were studied. Implanted iPSs\nwere tracked by the SRY gene expression analysis. Both treatments minimized elevation in serum creatinine, significantly\nimproved clearance, and slowed down progression of disease. The proteinuria was reduced only in the iPS group. Both\ntreatments reduced glomerulosclerosis, iPSs decreased macrophage infiltration, and TGF-�² was reduced in kidneys from the\nBMSC group. Both types of treatments increased VEGF gene expression, TGF-�² was upregulated only in the iPS group,\nand IL-10 had low expression in both groups. The SRY gene was found in 5/8 rats treated with iPSs. These 5 animals presented\ntumors with histology and cells highly staining positive for PCNA and Wilmsâ�� tumor protein antibody characteristics of Wilmsâ��\ntumor. These results suggest that iPSs may be efficient to retard progression of CKD but carry the risk of Wilmsâ�� tumor development....
Background: Transplantation of mesenchymal stem cells (MSC) has been proposed to improve wound healing. However,\nas these cells only transiently survive in the implantation site, the mechanisms underlying this beneficial healing response\nare associated with restorative paracrine effects of MSC matricellular factors on resident stromal cells. However, this requires\nthat the recipient has a robust reservoir of viable cells. Here, we examine the influence of MSCs on the behavior\nof cotransplanted fibroblasts, in a manner to provide augmented cellular reserve to debilitated individuals, specifically\nfocusing on matrix remodeling following in-vivo wounding.\nMethods: Using a Hylan-A dermal filler hydrogel containing collagen I and tenascin-C for delivery and increased survival\nof transplanted cells, we find that cotransplantation of MSCs with fibroblasts reduces scarring.\nResults: Transplanted xenogeneic MSCs augmented fibroblast proliferation, migration, and extracellular matrix deposition\ncritical for wound closure, and reduced inflammation following wounding. MSCs also corrected matrix remodeling by\nCXCR3-deficient fibroblasts which otherwise led to hypertrophic scarring. This effect was superior to MSC or fibroblast\ntransplantation alone.\nConclusions: Taken together, these data suggest that MSCs, even if eventually rejected, transplanted with fibroblasts\nnormalize matrix regeneration during healing. The current study provides insight into cellular therapies as a viable\nmethod for antifibrotic treatment and demonstrates that even transiently engrafted cells can have a long-term impact\nvia matrix modulation and education of other tissue cells....
Ischemic stroke, the most common subtype of stroke, has been one of the leading causes of mobility and mortality worldwide.\nHowever, it is still lacking of efficient agents. Stem cell therapy, with its vigorous advantages, has attracted researchers around\nthe world. Numerous experimental researches in animal models of stroke have demonstrated the promising efficacy in treating\nischemic stroke. The underlying mechanism involved antiapoptosis, anti-inflammation, promotion of angiogenesis and\nneurogenesis, formation of new neural cells and neuronal circuitry, antioxidation, and blood-brain barrier (BBB) protection.\nThis review would focus on the types and neuroprotective actions of stem cells and its potential mechanisms for ischemic stroke....
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