Ischemia/reperfusion injury promotes and granulocyte-colony stimulating factor inhibits migration of bone marrow-derived stem cells to endometrium.
The endometrium is a dynamic tissue that undergoes repeated rounds of regeneration in each reproductive (estrous or menstrual) cycle. We have previously shown that bone marrow (BM)-derived stem cells engraft the endometrium in rodents and humans; however, it is not known if these cells contribute physiologically to uterine cyclic regeneration or alternatively are primarily involved in uterine repair in response to injury. Here we performed male-to-female BM transplant and tested the ability of uterine injury to recruit BM-derived cells to endometrium in the presence and absence of sex steroids. Uterine ischemia/reperfusion injury resulted in an ~2-fold increase in BM-derived stem cell recruitment to the endometrium. The effect was independent of sex steroids or the existence of an estrous cycle. BM-derived mesenchymal stem cells (MSCs) are involved in uterine repair after injury, but not the cyclic regeneration of the endometrium in the estrous/menstrual cycle. Granulocyte-colony stimulating factor (G-CSF) is used to increase BM mobilization for transplant and has been proposed as a means of mobilizing stem cells to the uterus. Here G-CSF treatment led to decreased BM engraftment of the uterus after injury, likely by favoring mobilization of hematopoietic stem cells over the MSCs. G-CSF is unlikely to be of benefit in repair of uterine injury in humans. Taken together, we demonstrate that ischemic injury drives BM MSC engraftment of the uterus, independent of estrous cycle, sex steroids, or G-CSF.
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, New Haven, CT, USA.
Hongling
H
Du
Hanyia
H
Naqvi
Hugh S
HS
Taylor
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D004717:Endometrium; D030762:Estrous Cycle / Q000187:drug effects / Q000502:physiology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012038:Regeneration; D015427:Reperfusion Injury / Q000188:drug therapy*; D013234:Stem Cells / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
D016179:Granulocyte Colony-Stimulating Factor