Compared to embryonic and induced pluripotent stem cells, mesenchymal stem/stromal cells (MSCs) have made their presence felt with good therapeutic promise and safety profile. Transplanting MSCs has successfully helped to reverse infertility and resulted in live births in animal models and also in humans. But the underlying mechanism for their therapeutic potential is not yet clear. MSCs are not pluripotent and hence lack plasticity to differentiate into multiple adult cell types. They rather act as ‘paracrine providers’ to the tissue-resident stem cells since similar beneficial effects are also observed when their secretome (microvesicles or exosomes) is transplanted. Cytokines, growth factors, signaling lipids, mRNAs, and miRNAs secreted by MSCs enables tissue-resident stem cells to undergo differentiation into specific cell types. Tissue-resident stem cells include pluripotent, very small embryonic-like stem cells (VSELs) and progenitors [spermatogonial (SSCs), ovarian (OSCs) and endometrial (EnSCs) stem cells in testes, ovary and uterus respectively] which function in a subtle manner to maintain life-long tissue homeostasis and regenerate damaged (non-functional) reproductive tissues by differentiating into sperm, oocytes and endometrial epithelial cells respectively. Similar to restoring spermatogenesis, primordial follicles numbers are increased upon transplanting MSCs. Published literature suggests that MSCs do not differentiate into epithelial cells in the endometrium. Nuclear OCT-4 positive VSELs and cytoplasmic OCT-4, AXIN2 and KERATIN-19 positive epithelial progenitors have a greater role during endometrial regeneration. We propose, transplantation of MSCs simply provides growth factors/cytokines essential for the tissue-resident stem/progenitor cells to undergo differentiation into sperm, eggs and endometrial epithelial cells in the reproductive tissues.

与胚胎干细胞和诱导多能干细胞相比，间充质干/基质细胞 (MSCs) 的存在具有良好的治疗前景和安全性。移植间充质干细胞已成功帮助逆转不孕症，并在动物模型和人类中实现了活产。但其治疗潜力的潜在机制尚不清楚。间充质干细胞不是多能的，因此缺乏分化成多种成体细胞类型的可塑性。它们宁愿充当组织驻留干细胞的“旁分泌提供者”，因为在移植它们的分泌组（微泡或外泌体）时也观察到类似的有益效果。MSC 分泌的细胞因子、生长因子、信号脂质、mRNA 和 miRNA 使组织驻留干细胞能够分化成特定的细胞类型。组织驻留干细胞包括多能、非常小的胚胎样干细胞 (VSEL) 和祖细胞 [分别位于睾丸、卵巢和子宫中的精原细胞 (SSC)、卵巢 (OSC) 和子宫内膜 (EnSC) 干细胞]通过分别分化为精子、卵母细胞和子宫内膜上皮细胞来维持终生组织稳态和再生受损（非功能性）生殖组织。与恢复精子发生相似，移植 MSC 后原始卵泡数量增加。已发表的文献表明，MSCs 不会在子宫内膜中分化成上皮细胞。核 OCT-4 阳性 VSEL 和细胞质 OCT-4、AXIN2 和 KERATIN-19 阳性上皮祖细胞在子宫内膜再生过程中发挥更大的作用。我们建议，