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Allogeneic rejection of embryonic stem cells

Monday May 4th, 2009 @ 02:15:43 EST

From Category: Embryonic
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Nara, Japan -

Seeing stem cell therapy as sources of cytokines or angiogenic factors allows the possibility that the stem cell will eventually be rejected but the therapeutic effect will remain.  For example, mesenchymal stem cells are known to secrete various immune modulatory factors, such as soluble HLA-G, which allows them to suppress inflammation.  If mesenchymal stem cells are subsequently cleared by the immune system, theoretically it does not matter to the therapeutic response because the cells have already accomplished what was needed of them.  This is perhaps why universal donor mesenchymal stem cells are being administered in an undifferentiated state.  This form of administration allows for: a) homing to injury.  The undifferentiated cells will have a much higher propensity to home to injured tissue as compared to non-differentiated cells; and b) immune evasion.  Undifferentiated cells contain low expression of HLA and differentiation markers, making them relatively inert. Currently mesenchymal stem cells are or have been in clinical trials for heart failure, graft versus host disease, and type 1 diabetes.

In contrast to mesenchymal stem cells, which can be injected intravenously in an undifferentiated state, embryonic stem cells can not be administered as undifferentiated cells since they will cause teratomas.  Since they require differentiation, the issue of rejection becomes a problem.  

In a recent paper (Toriumi et al. Treatment of Parkinson's disease model mice with allogeneic embryonic stem cells: necessity of immunosuppressive treatment for sustained improvement. Neurol Res 2009 Apr;31(3):220-7) the issue of embryonic stem cell allogeneic rejection after differentiation was addressed.

The investigators used a mouse model of Parkinson's induced by injection of 6-hydroxydopamine in syngeneic and allogeneic strains of mice.  Animals were administered embryonic stem cell derived tyrosine hydroxylase positive neurons that were developed in vitro through an embryoid body multistep differentiation protocol.  The cells were grafted intracranially in the recipients.

Although functional improvement was seen with both the allogeneic and syngeneic neurons.  Benefit was lost in allogeneic recipients that did not recieve immune suppression. 

These data point to the possibility that embryonic stem cell derived cellular products, unless they are autologous, will require some form of long term immune suppression.


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