Three general properties:

they are capable of dividing themselves for long periods;

they are unspecialized;

and they can give rise to specialized cell types.

What are Stem Cells

This cellCan form the

Embryo and placenta

This cellCan just form the

embryo

Fully mature

Totipotent Differentiation into

ANY cell type Known Source Large numbers can be

harvested from embryos May cause immune

rejection

Rejection of ES cells by recipient has not been shown yet

Multi or pluripotent Differentiation into

some cell types, limited outcomes

Unknown source Limited numbers, more

difficult to isolate Less likely to cause

immune rejection, since the patient’s own cells can be used

Embryonic VS Adult Stem Cells

First isolated by Friedenstein et al in 1970 from bone marrow

Fibroblastoid cells - spindle-shaped

Adherent to tissue culture glass or plastic

High growth potential

What are Mesenchymal Stem Cells

Differentiation capacity

Can differentiate into: Osteoblasts Adipocytes chondrocytes myocytes neuron-like cells.

Multipotent

Sources of MSCs

Morphological and physical features

Plastic-adherent, fibroblast-like cells

Cell surface markers

CD34negˬ CD45negˬCD14 negˬCD31neg Hematopoietic markers:

CD29posˬ CD44posˬCD54posˬ CD56posˬCD73posˬCD105posˬAdhesion molecules: CD106 pos

CD104posˬCD61posˬCD49pos Integrins:

Growth factors and Cytokines: CDw119pos, CD140apos, CD126pos, CD124pos, CD123pos, CD121pos, CD120pos, CD71pos

White blood cell common antigens: CD80neg, CD3neg, CD86neg, MHC Class II Antigensneg

Functional features

Potential to differentiate into the osteogenic, chondrogenic, adipogenic, tenogenic, myogenic, neural cells and other lineages.

Phenotypic Receptors

The International Society for Cellular therapy (ISCT) has devised three criteria needed to identify MSCs: plastic adherence of the isolated cells in culture.

Expression of culture of differentiation (CD) markers such as CD105, CD73, CD90 and in >95% of the culture with absent expression of markers including CD34, CD45, CD14 or CD11B, CD79A or CD19 and human leukocyte antigen-DR(HLA-DR).

capacity to differentiate in to osteocytes, adipocytes and chondrocytes.

Human Mesenchymal Stem Cell Markers

Sox2Oct4NanogSSEA-4,3(Rastegar et al., 2010)CD271(Docheva et al., 2008)CD146(Docheva et al., 2008)GD2(Martinez et al., 2007)

Asumda and Chase, 2011

Numerous factors including culture parameters such as:Nutritional levelCell confluenceOxygen level Number of passagesPlastic surface

Culture and expansion of MSCs

Important factors that regulate differentiation and proliferation capacity

Telomere length

Asymmetric cell division

Multiipotent - self renewal and wide differentiation into multiple lineages

Can be incorporated direct into other tissues Low immunogenicity and suppress alloreactive T

cell response (transplanted allogenic MSC are not rejected)

Easy to obtain

Regenerative medicine and Therapeutic issues

Appealing Charactersitics

MSC migration toward injury tissue

Immunomodulatory properties of MSCs