Download 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.
2.
3.
4.
Nardi, N. Beyer et al. Stem Cells. 2006
Oni OO et al. J Bone Joint Surg Am. 1992
Brighton CT et al. J Orthop Trauma. 1997
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 cytokines
Jiang Y et al. Nature, 2002
Franco Lambert AP et al. Differentiation.
2009
Engler AJ et al. Cell. 2006
Ryan JM et al. Journal of Inflammation. 2005
Ryan JM et al. Clinical & Experimental Immunology. 2007
Phinney 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 repair
 orthopedic applications
 chondral defects
……
Heirani-Tabasi A et al. Journal of Genes and Cells. 2015
Manieri NA et al. Current Opinion in Gastroenterology. 2011
Fischer UM et al. Stem Cells and Development. 2009
Wakitani 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 transplantation
 GVHD
 Corticosteroids

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 factors
 Genetic modifications, pdx1
Hepatocytes
 cardiac tissues

 cardiac myocytes

Ectodermal differentiation
 neurons, and astrocytes
GENE CARRIERS
cytoprotective effects and lead to tissue
repair
Genetic modifications of MSCs have been
performed to improve the MSC efficacy in
tissue repair/regeneration
 Secretion of growth factors

 neurotropic factors
 Liver tp, HGF, BDNF, IGF-1 and VEGF
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