Mervin C. Yoder, MD

While it is well founded that all hematopoietic cells circulating in blood or present in tissues are derived from bone marrow resident hematopoietic stem cells (HSC) in adult subjects, Dr. Yoder has contributed to the more recent understanding that there are multiple waves of hematopoiesis that emerge throughout embryonic and fetal development in mouse and man. The first wave of blood cells are derived from hemogenic endothelial cells within the yolk sac. During this wave, primitive red blood cells, macrophages and megakaryocytes are the first to emerge in the bloodstream (in that order).

Subsequently, in the second wave, erythroid-myeloid progenitor cells, B1B and T cells, and NK cells emerge from hemogenic endothelial cells. Finally, in the third wave, HSC emerge from specific hemogenic endothelium in the aorta. These HSC migrate to fetal liver, expand, and subsequently migrate again into the bone marrow sites of hematopoiesis that persist throughout the life of the subject.

In related studies, Dr. Yoder contributed to clarifying the identity, source and function of circulating and resident vascular endothelial progenitor cells. Human cord blood was found to be enriched in circulating endothelial cells that displayed clonal proliferative potential (named endothelial colony forming cells:ECFC). ECFC are present not only in cord blood, but also within the endothelial intima of umbilical artery and vein, adult mammary artery, saphenous vein and aortic vessels. ECFC upon isolation display a hierarchy of proliferative potential with some individual cells giving rise to >2,000 progeny in 14 days. Recently, cells resembling ECFC have been identified upon specific differentiation of induced pluripotent stem cells and such cells integrate into damaged diabetic murine retinal vasculature to restore retinal perfusion, diminish retinal hypoxia and stimulate recovery of retinal neuronal functions.

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