shen bin 9-20-2015 journal club. what is mscs? mesenchymal stem cells (mscs) are multipotent...
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MESENCHYMAL STEM/STROMAL
CELL
Shen Bin
9-20-2015
Journal Club
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What is MSCs? Mesenchymal stem cells
(MSCs) are multipotent stromal cells that can differentiate into a variety of cell types [1] including: osteoblasts (bone cells) [2] chondrocytes (cartilage cells) [3] myocytes (muscle cells)[4] and adipocytes (fat cells).
1. Nardi, N. Beyer et al. Stem Cells. 20062. Oni OO et al. J Bone Joint Surg Am. 19923. Brighton CT et al. J Orthop Trauma. 19974. Pittenger et al. Science. 1999
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CHARACTERISTICS Morphology
Fibroblast-like Detection
Express :CD73, CD90 and CD105 Lacking the expression: CD11b, CD14, CD19, CD34, CD45,
CD79a and HLA-DR Self-renewal and differentiation capacity
Great capacity for self-renewal osteoblasts, adipocytes, and chondrocytes, myocytes
neurons, hepatocyte and beta-like cells. Immunomodulatory effects
avoid allorecognition○ interfere with dendritic cell and T-cell function○ secreting cytokinesJiang Y et al. Nature, 2002
Franco Lambert AP et al. Differentiation. 2009Engler AJ et al. Cell. 2006
Ryan JM et al. Journal of Inflammation. 2005Ryan JM et al. Clinical & Experimental Immunology. 2007Phinney DG et al. Stem Cells. 2007
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MEDICAL USE Intravenous transplantation
systemic diseases like graft versus host disease and sepsis
Increase the local concentration of cells inflammatory bowel disease
Direct injection or placement of cells into a site in need of repairorthopedic applications chondral defects
…… Heirani-Tabasi A et al. Journal of Genes and Cells. 2015Manieri NA et al. Current Opinion in Gastroenterology. 2011Fischer UM et al. Stem Cells and Development. 2009Wakitani S et al. Journal of Tissue Engineering and Regenerative Medicine . 2007
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IMMUNOMODULATION
MSCs effect proliferation, maturation and cytokine secretion by different immune cells. NK cells, Natural Killer Cells; iDCs, Immature Dendritic Cells; APCs, Antigen Presenting Cells.
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CELL AND ORGAN TRANSPLANTATION
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Graft vs. Host Disease
HSC transplantationGVHDCorticosteroids
MSCs from the donor and controls inhibited patient lymphocyte proliferation by 90% before and after transplantation
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REGENERATIVE MEDICINES Transdifferentiation of MSCs to β cells
Small molecular chemicals, growth factorsGenetic modifications, pdx1
Hepatocytes cardiac tissues
cardiac myocytes Ectodermal differentiation
neurons, and astrocytes
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GENE CARRIERS
Genetic modifications of MSCs have been performed to improve the MSC efficacy in tissue repair/regeneration
Secretion of growth factorsneurotropic factorsLiver tp, HGF, BDNF, IGF-1 and VEGF
cytoprotective effects and lead to tissue repair
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CHALLENGES TO MSC-BASED THERAPY poor delivery of MSCs spontaneous malignant transformation
of MSCs unwanted differentiation
MSC differentiation to myofibroblasts instead of hepatocytes is unwanted and leads to worsening of liver injury
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CLINICAL TRIALS
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THANKS