Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China.
Laboratory of Molecular Diagnosis and Regenerative Medicine, Medical Research Center, The Affiliate Hospital of Qingdao University, Qingdao, 266000, People's Republic of China.
Stem Cell Res Ther. 2022 Jun 21;13(1):267. doi: 10.1186/s13287-022-02916-x.
Mesenchymal stem cells (MSCs) are a heterogeneous group of subpopulations with differentially expressed surface markers. CD146 + MSCs correlate with high therapeutic and secretory potency. However, their therapeutic efficacy and mechanisms in premature ovarian failure (POF) have not been explored.
The umbilical cord (UC)-derived CD146 +/- MSCs were sorted using magnetic beads. The proliferation of MSCs was assayed by dye670 staining and flow cytometry. A mouse POF model was established by injection of cyclophosphamide and busulfan, followed by treatment with CD146 +/- MSCs. The therapeutic effect of CD146 +/- MSCs was evaluated based on body weight, hormone levels, follicle count and reproductive ability. Differential gene expression was identified by mRNA sequencing and validated by RT-PCR. The lymphocyte percentage was detected by flow cytometry.
CD146 +/- MSCs had similar morphology and surface marker expression. However, CD146 + MSCs exhibited a significantly stronger proliferation ability. Gene profiles revealed that CD146 + MSCs had a lower levels of immunoregulatory factor expression. CD146 + MSCs exhibited a stronger ability to inhibit T cell proliferation. CD146 +/- MSCs treatment markedly restored FSH and E2 hormone secretion level, reduced follicular atresia, and increased sinus follicle numbers in a mouse POF model. The recovery function of CD146 + MSCs in a reproductive assay was slightly improved than that of CD146 - MSCs. Ovary mRNA sequencing data indicated that UC-MSCs therapy improved ovarian endocrine locally, which was through PPAR and cholesterol metabolism pathways. The percentages of CD3, CD4, and CD8 lymphocytes were significantly reduced in the POF group compared to the control group. CD146 + MSCs treatment significantly reversed the changes in lymphocyte percentages. Meanwhile, CD146 - MSCs could not improve the decrease in CD4/8 ratio induced by chemotherapy.
UC-MSCs therapy improved premature ovarian failure significantly. CD146 +/- MSCs both had similar therapeutic effects in repairing reproductive ability. CD146 + MSCs had advantages in modulating immunology and cell proliferation characteristics.
间充质干细胞（MSCs）是一群具有不同表面标志物表达的异质亚群。CD146+MSC 与高治疗和分泌潜能相关。然而，它们在卵巢早衰（POF）中的治疗效果和机制尚未得到探索。
使用磁珠分选脐带（UC）来源的 CD146+/-MSC。通过染料 670 染色和流式细胞术检测 MSC 的增殖。通过注射环磷酰胺和白消安建立小鼠 POF 模型，然后用 CD146+/-MSC 治疗。根据体重、激素水平、卵泡计数和生殖能力评估 CD146+/-MSC 的治疗效果。通过 mRNA 测序鉴定差异基因表达，并通过 RT-PCR 进行验证。通过流式细胞术检测淋巴细胞百分比。
CD146+/-MSC 具有相似的形态和表面标志物表达。然而，CD146+MSC 表现出更强的增殖能力。基因谱显示 CD146+MSC 表达的免疫调节因子水平较低。CD146+MSC 抑制 T 细胞增殖的能力更强。CD146+/-MSC 治疗可显著恢复 FSH 和 E2 激素分泌水平，减少卵泡闭锁，并增加小鼠 POF 模型中的窦卵泡数量。在生殖试验中，CD146+MSC 的恢复功能略优于 CD146-MSC。UC-MSC 治疗可改善卵巢局部内分泌功能，这是通过过氧化物酶体增殖物激活受体（PPAR）和胆固醇代谢途径实现的。与对照组相比，POF 组的 CD3、CD4 和 CD8 淋巴细胞百分比显著降低。CD146+MSC 治疗可显著逆转淋巴细胞百分比的变化。同时，CD146-MSC 不能改善化疗引起的 CD4/8 比值降低。
UC-MSC 治疗可显著改善卵巢早衰。CD146+/-MSC 在修复生殖能力方面均具有相似的治疗效果。CD146+MSC 在调节免疫和细胞增殖特征方面具有优势。
