Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA.
Reprod Sci. 2022 Aug;29(8):2382-2390. doi: 10.1007/s43032-021-00738-5. Epub 2021 Sep 13.
Regeneration of uterine tissue is an important physiological process that allows for maintenance of fertility after menstruation or pregnancy. Stem cells, especially bone marrow-derived progenitors, play a crucial role in this regeneration. Here, we describe the conversion of DsRed-labeled bone marrow-derived stem cells (BMDSCs) into specific uterine cell types with both differentiated and stem cell properties in a murine model. Irradiated recipient mice underwent bone marrow transplant with DsRed-expressing BMDSCs and were analyzed for engraftment and differentiation of BMDSCs in the uterus after 2, 6, and 16 weeks. Microarray and qRT-PCR analysis of bone marrow-derived cells obtained from the uterus identified upregulation of markers indicating a contribution to the population of stromal, epithelial, endothelial, and muscle cells, followed by a late expansion of epithelial cells. Other engrafted BMDSCs in the uterus were characterized by the continued expression of specific stem cell markers such as Sca1, CD44, CD146, and CD133, indicating the some BMDSCs remain as progenitor cells. BMDSCs established in recipient mice by the 16th week were sorted by flow cytometry using DsRed and progenitor cell surface markers. In vitro cell culture studies showed that single sorted cells had clonogenic properties. These results suggest that engrafted BMDSCs in the uterus had both a stem cell component and were able to differentiate into several differentiated cell types. The pool of progenitor cells likely continues to supply differentiated uterine cells in the process of uterine repair and remodeling.
子宫组织的再生是一个重要的生理过程，它允许在月经或怀孕后维持生育能力。干细胞，特别是骨髓来源的祖细胞，在这种再生中起着至关重要的作用。在这里，我们描述了在小鼠模型中，DsRed 标记的骨髓来源干细胞（BMDSCs）转化为具有分化和干细胞特性的特定子宫细胞类型的过程。辐照后的受体小鼠接受了表达 DsRed 的 BMDSCs 的骨髓移植，并在 2、6 和 16 周后分析了 BMDSCs 在子宫中的植入和分化情况。从子宫中获得的骨髓来源细胞的微阵列和 qRT-PCR 分析表明，标记物的上调表明对基质、上皮、内皮和肌肉细胞群体的贡献，随后上皮细胞的扩张。其他植入子宫的 BMDSCs 的特征是持续表达特定的干细胞标记物，如 Sca1、CD44、CD146 和 CD133，表明一些 BMDSCs 仍然是祖细胞。通过第 16 周在受体小鼠中建立的 BMDSCs 通过 DsRed 和祖细胞表面标记物的流式细胞术进行分选。体外细胞培养研究表明，单个分选细胞具有克隆形成特性。这些结果表明，植入子宫的 BMDSCs 既有干细胞成分，又能分化为几种分化细胞类型。祖细胞池可能在子宫修复和重塑过程中继续为分化的子宫细胞提供补充。
