Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, New Haven, CT, USA.
Stem Cells Dev. 2012 Dec 10;21(18):3324-31. doi: 10.1089/scd.2011.0193. Epub 2012 Aug 16.
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.
子宫内膜是一种具有动态特性的组织，在每个生殖（发情或月经）周期中都会经历反复的再生。我们之前已经表明，骨髓（BM）衍生的干细胞在啮齿动物和人类中植入子宫内膜；然而，尚不清楚这些细胞是否对子宫周期性再生具有生理贡献，或者它们主要参与对损伤的子宫修复。在这里，我们进行了雄性到雌性的 BM 移植，并测试了在存在和不存在性激素的情况下，子宫损伤招募 BM 衍生细胞到子宫内膜的能力。子宫缺血/再灌注损伤导致 BM 衍生干细胞向子宫内膜的募集增加了约 2 倍。这种作用不依赖于性激素或发情周期的存在。BM 衍生的间充质干细胞（MSCs）参与损伤后的子宫修复，但不参与发情/月经周期中子宫内膜的周期性再生。粒细胞集落刺激因子（G-CSF）用于增加 BM 移植的动员，并且被提议作为将干细胞动员到子宫的一种手段。在这里，G-CSF 治疗导致损伤后 BM 对子宫的植入减少，可能是通过有利于造血干细胞而不是 MSCs 的动员。G-CSF 不太可能对人类子宫损伤的修复有益。综上所述，我们证明缺血性损伤驱动 BM MSC 对子宫的植入，不依赖于发情周期、性激素或 G-CSF。
