Post on 03-Jan-2016
MESENCHYMAL STEM/STROMAL
CELL
Shen Bin
9-20-2015
Journal Club
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
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
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
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.
CELL AND ORGAN TRANSPLANTATION
Graft vs. Host Disease
HSC transplantationGVHDCorticosteroids
MSCs from the donor and controls inhibited patient lymphocyte proliferation by 90% before and after transplantation
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
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
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
CLINICAL TRIALS
THANKS