Erythropoietin (EPO) is a glycoprotein that regulates the growth and differentiation of erythroid progenitor cells. Erythropoietin (EPO) reportedly mediates the proliferation and apoptosis of a variety of non-hematopoietic cells through the erythropoietin receptor (EPOR). The surface of bone marrow-derived mesenchymal stem cells also expresses erythropoietin receptor (EPOR). One previous study showed that Erythropoietin (EPO) promotes the proliferation of mouse bone marrow-derived mesenchymal stem cell and reduces their rate of apoptosis in vitro under AKI microenvironment conditions, effects that are mediated by EPOR.
High systemic levels of Erythropoietin (EPO) reprogram the transcriptomes of multi- and bipotent hematopoietic stem/progenitor cells in vivo. This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells and committed erythroid progenitors, leading to increased erythroid and decreased myeloid hematopoietic stem cell output.
The Epo–Epo receptor signaling pathway, although dispensable for the formation of erythroid progenitors, is essential for their subsequent proliferationand survival. The effect of increased Erythropoietin (EPO) production is therefore generally believed to be due to improved expansion of committed erythroid progenitors. Multipotent hematopoietic cells have been shown to express functional Epo receptor.
Treatment with Erythropoietin (EPO) was shown to protect human adipose tissue derived mesenchymal stem cells in an ischemic injury in vitro model. The analyses indicated that expression of Erythropoietin (EPO) receptors played a pivotal role in Erythropoietin (EPO) mediated cell survival. In this study, the anti-apoptotic effect of Erythropoietin (EPO) on stem cells was analyzed in apoptosis-induced human mesenchymal stem cells. Apoptosis was induced in cultured adult human adipose tissue derived mesenchymal stem cells by hydrogen peroxide. A group of cultured cells was also treated with recombinant human Erythropoietin (EPO) in a concentration of 50ng/mL.The degree of apoptosis was analyzed by ﬂow-cytometry and immunohistochemical staining for Caspase 3. The average percentages of apoptotic cells were signiﬁcantly higher in H2O2 -induced stem cells than in cells co-cultured with erythropoietin (63.03 ± 4.96% vs29 ± 3.41%, p <0.01). It is concluded that preconditioning with Erythropoietin (EPO) suppresses apoptosis of mesenchymal stem cells and enhances their survival.
Erythropoietin (EPO) has been demonstrated to be a type of tissue protection factor, which exerts neurotrophic and neuroprotective effects. Yuan et al observed the effects of erythropoietin on the differentiation of embryonic cerebral cortex neural stem cells of rats cultured in vitro, the results indicated that erythropoietin is able to promote the differentiation of neural stem cells into neurons.
• Ercan E, et al. In vitro protection of adipose tissue-derived mesenchymal stem cells by erythropoietin[J]. Acta histochemica, 2014, 116(1): 117-125.
• Liu N M, et al. Effect of erythropoietin on mesenchymal stem cell differentiation and secretion in vitro in an acute kidney injury microenvironment[J]. Genet Mol Res, 2013, 12: 6477-6487.
• Grover A, et al. Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate[J]. Journal of Experimental Medicine, 2014, 211(2): 181-188.
• Zhao Y, et al. Neural stem cell transplantation combined with erythropoietin for the treatment of spinal cord injury in rats[J]. Experimental and therapeutic medicine, 2016, 12(4): 2688-2694.