Mesenchymal stem cell-based therapy: a new paradigm in regenerative medicine. J Cell Mol Med

Stem Cell and Gene Therapy Research Group, Institute of Nuclear Medicine and Allied Sciences, Lucknow Road, Timarpur, Delhi, India.
Journal of Cellular and Molecular Medicine (Impact Factor: 4.01). 08/2009; 13(11-12):4385-402. DOI: 10.1111/j.1582-4934.2009.00857.x
Source: PubMed


Mesenchymal stem cells (MSCs), adherent fibroblastoid cells, present in bone marrow and many other tissues can be easily isolated and expanded in vitro. They are capable of differentiating into different cell types such as osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial cells and neuronal cells. Such immense plasticity coupled with their ability to modulate the activity of immune cells makes them attractive for stem cell-based therapy aimed at treating previously incurable disorders. Preclinical studies have reported successful use of MSCs for delivering therapeutic proteins and repairing defects in a variety of disease models. These studies highlighted the in vivo potential of MSCs and their ability to home to injury sites and modify the microenvironment by secreting paracrine factors to augment tissue repair. Their therapeutic applicability has been widened by genetic modification to enhance differentiation and tissue targeting, and use in tissue engineering. Clinical trials for diseases such as osteogenesis imperfecta, graft-versus-host disease and myocardial infarction have shown some promise, demonstrating the safe use of both allogeneic and autologous cells. However, lack of knowledge of MSC behaviour and responses in vitro and in vivo force the need for basic and animal studies before heading to the clinic. Contrasting reports on immunomodulatory functions and tumorigenicity along with issues such as mode of cell delivery, lack of specific marker, low survival and engraftment require urgent attention to harness the potential of MSC-based therapy in the near future.

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    • "Owing to their ability to differentiate into cells of mesenchymal lineages and to their unique immune properties, MSCs have been tested in clinical trials for a variety of diseases including graft vs. host disease (GVHD), myocardial infarction, osteogenesis imperfecta, and other diseases [5] [6]. "
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    ABSTRACT: Isolates of mesenchymal stromal cells (MSCs) contain a mixed cell population of stem cells, multipotent and unipotent progenitors, and differentiated cells. It is speculated that the useful subpopulation for tissue engineering and cell therapy will be the multipotent progenitor cells or the stem cells. The colony forming unit-fibroblast (CFU-F) assay is an in vitro assay for clonogenicity, which is one property of the stem/progenitor cell population of MSCs. Our goal was to generate standard protocols that would permit the expansion and maintenance of CFU-F. Previous work reported that low plating density and/or exposure to 5% oxygen vs. 21% oxygen increased proliferation rate and enhanced expansion of MSCs. Here, we characterized the effect of both plating density and oxygen concentration on MSCs derived from Wharton's jelly (WJCs). We found that reducing oxygen concentration from 21% (room air) to 5% during expansion increased cell yield and maintained CFU-F, without affecting the expression of surface markers or the differentiation capacity of WJCs. In addition, reducing plating density from 100 cells/cm 2 to 10 cells/cm 2 increased CFU-F frequency. Therefore, plating density and oxygen concentration are two important variables that affect the expansion rate and frequency of CFU-F of WJCs. These results suggest that these two variables might be used to produce different input populations for tissue engineering or cellular therapy.
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    • "In order to improve the feasibility of islet transplantation for the treatment of diabetes, it has been proposed to associate pancreatic islets with Mesenchymal Stem Cells (MSCs), a population of adult stem cells initially identified in bone marrow and then found also in other tissues such as adipose tissue, skin, and amniotic fluid [4]. MSCs are easily harvestable from patients, with high plasticity [5], immunomodulatory properties [6], and with the ability to support cellular survival both through direct contact [7], [8] and by the release of trophic factors [9], [10]. By means of these particular features it can be surmised that MSCs may improve the survival of pancreatic islets and, therefore, the success of the transplantation [11]–[13]. "
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    ABSTRACT: The clinical usability of pancreatic islet transplantation for the treatment of type I diabetes, despite some encouraging results, is currently hampered by the short lifespan of the transplanted tissue. In vivo studies have demonstrated that co-transplantation of Mesenchymal Stem Cells (MSCs) with transplanted pancreatic islets is more effective with respect to pancreatic islets alone in ensuring glycemia control in diabetic rats, but the molecular mechanisms of this action are still unclear. The aim of this study was to elucidate the molecular mechanisms of the positive effect of MSCs on pancreatic islet functionality by setting up direct, indirect and mixed co-cultures. MSCs were both able to prolong the survival of pancreatic islets, and to directly differentiate into an “insulin-releasing” phenotype. Two distinct mechanisms mediated these effects: i) the survival increase was observed in pancreatic islets indirectly co-cultured with MSCs, probably mediated by the trophic factors released by MSCs; ii) MSCs in direct contact with pancreatic islets started to express Pdx1, a pivotal gene of insulin production, and then differentiated into insulin releasing cells. These results demonstrate that MSCs may be useful for potentiating pancreatic islets' functionality and feasibility.
    PLoS ONE 01/2014; 9(1):e84309. DOI:10.1371/journal.pone.0084309 · 3.23 Impact Factor
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    • "Multipotent mesenchymal stem cells (MSCs) are a population of adult stem cells that can be easily isolated from various tissues and expanded in vitro. Many reports on their multipotency and possible clinical applications have raised hopes for and interest in regenerative medicine [1], [2]. Among MSCs from various sources, adipose stromal/stem cells (ASCs) have particularly attracted attention over the years because subcutaneous adipose tissue is accessible, abundant, and replenishable [3], [4]. "
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    ABSTRACT: Recent studies have shown that adipose-derived stromal/stem cells (ASCs) contain phenotypically and functionally heterogeneous subpopulations of cells, but their developmental origin and their relative differentiation potential remain elusive. In the present study, we aimed at investigating how and to what extent the neural crest contributes to ASCs using Cre-loxP-mediated fate mapping. ASCs harvested from subcutaneous fat depots of either adult P0-Cre/or Wnt1-Cre/Floxed-reporter mice contained a few neural crest-derived ASCs (NCDASCs). This subpopulation of cells was successfully expanded in vitro under standard culture conditions and their growth rate was comparable to non-neural crest derivatives. Although NCDASCs were positive for several mesenchymal stem cell markers as non-neural crest derivatives, they exhibited a unique bipolar or multipolar morphology with higher expression of markers for both neural crest progenitors (p75NTR, Nestin, and Sox2) and preadipocytes (CD24, CD34, S100, Pref-1, GATA2, and C/EBP-delta). NCDASCs were able to differentiate into adipocytes with high efficiency but their osteogenic and chondrogenic potential was markedly attenuated, indicating their commitment to adipogenesis. In vivo, a very small proportion of adipocytes were originated from the neural crest. In addition, p75NTR-positive neural crest-derived cells were identified along the vessels within the subcutaneous adipose tissue, but they were negative for mural and endothelial markers. These results demonstrate that ASCs contain neural crest-derived adipocyte-restricted progenitors whose phenotype is distinct from that of non-neural crest derivatives.
    PLoS ONE 12/2013; 8(12):e84206. DOI:10.1371/journal.pone.0084206 · 3.23 Impact Factor
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