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