Erythropoietin And Progenitor Cells
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Undifferentiated cells INCREASE when one bloodlets ..
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Erythropoietin signaling promotes transplanted progenitor cell
survival
Yi Jia1, Renaud Warin1, Xiaobing Yu, Reed Epstein and Constance Tom
Noguchi2
Molecular Medicine Branch, National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health,
Bethesda, Maryland, USA
(The FASEB Journal. 2009;23:3089-3099.)
2 Correspondence: Molecular Medicine Branch, NIDDK, National
Institutes of Health, Bldg. 10, Rm. 9N319, MSC-1822, 10 Center Dr.,
Bethesda, MD 20892-1822, USA. E-mail: cnog...@helix.nih.gov
We examine the potential for erythropoietin signaling to
promote donor cell survival in a model of myoblast
transplantation.
Expression of a truncated erythropoietin receptor in
hematopoietic stem cells has been shown to promote
selective engraftment in mice.
We previously demonstrated expression of endogenous
erythropoietin receptor on murine myoblasts, and
erythropoietin treatment can stimulate myoblast
proliferation and delay differentiation.
Here, we report that enhanced erythropoietin receptor
expression, as well as exogenous erythropoietin treatment
in myoblasts, provided a survival advantage and protection
against apoptosis under serum-starvation conditions.
When cultured in differentiation medium, expression of
the myogenic regulatory proteins shifted toward early
differentiation with increased erythropoietin receptor.
Expression of early myogenic differentiation proteins
Myf-5 and MyoD increased, while later stage protein
myogenin decreased.
Transplantation of C2C12 myoblasts overexpressing
truncated erythropoietin receptor showed more transplanted
cell incorporation into muscle fibers in muscular dystrophy
mdx mice.
These cells also restored dystrophin protein expression
in mdx mice at 6 wk after cell treatment that was further
increased with exogenous erythropoietin administration.
In summary, enhanced erythropoietin receptor expression
promotes transplanted cell survival in a mouse model for
myoblast transplantation and provides dystrophin
expression in mice with muscular dystrophy.
—Jia, Y., Warin, R., Yu, X., Epstein, R., Noguchi, C. T.
Erythropoietin signaling promotes transplanted progenitor
cell survival.
Key Words: myoblast • dystrophin • transplantation • receptor • EpoR
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