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What are Stem Cells
Three general properties:
they are capable of dividing themselves for long
periods;
they are unspecialized;
and they can give rise to specialized cell types.
Embryonic stem cells (ESC)
Fetus stem cells (FSC)
Adult stem cells (ASC)
This cell
Can form the
Embryo and placenta
This cell
Can just form the
embryo
Fully mature
Embryonic VS Adult Stem Cells
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

What are Mesenchymal 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
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
Hematopoietic markers: CD31neg CD14 neg CD45neg CD34neg
Adhesion molecules: CD106 pos CD105pos CD73pos CD56pos CD54pos CD44pos CD29pos
Integrins: CD49pos CD61pos CD104pos
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 antigenDR(HLA-DR).

capacity to differentiate in to osteocytes,
adipocytes and chondrocytes.
Human Mesenchymal
Stem Cell Markers

Sox2

Oct4

Nanog

SSEA-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
Culture and expansion of MSCs
Numerous factors including culture parameters
such as:
 Nutritional level
 Cell confluence
 Oxygen level
 Number of passages
 Plastic surface
Important factors that regulate differentiation and
proliferation capacity
 Telomere
length
 Asymmetric
cell division
Appealing Charactersitics
 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
MSC migration toward injury tissue
Immunomodulatory properties of MSCs