Department of Pediatric Disease, School of Medicine, Motahari Hospital, Urmia University of Medical Sciences, Urmia, Iran.
Fertility and Infertility Research Center, Besat Medical Education and Treatment Center, Kurdistan University of Medical Sciences, Kurdistan, Iran.
Taiwan J Obstet Gynecol. 2023 Sep;62(5):667-676. doi: 10.1016/j.tjog.2023.07.007.
Exposure of stem cells to sublethal levels of hydrogen peroxide (HO) can prevent oxidative stress-induced apoptosis. In the present study, the effects of HO preconditioning on the therapeutic potential of human umbilical vein cord mesenchymal stem cells (hUCV-MSCs) were evaluated in a murine model of premature ovarian failure.
Mature mice were divided into 4 groups, and 10 mice were incorporated into each group. The control (Ctrl) group received phosphate buffered saline (PBS) intraperitoneal (IP), and the CTX group was injected IP with cyclophosphamide (CTX). The CTX + MSC group after receiving CTX was injected with a single dose of hUCV-MSCs labeled with CM-DiI intravenously (IV), whereas the CTX + preMSCs group after CTX injection received preconditioned MSCs with HO IV. Seven days later, the mice were euthanized, and their ovaries were removed for histological studies such as H&E staining and the TUNEL assay. Furthermore, the numbers of CM-DiI-labeled hUCV-MSCs in the different regions of the ovary were calculated. FSH and estradiol values in the serum were measured.
Our studies showed that CTX caused degenerative changes and follicular loss in the ovary. The number of follicles in the CTX + MSCs and CTX + PreMSCs groups was significantly higher compared to the CTX group. In addition, in the CTX + PreMSCs group, the numbers of different types of follicles were higher than in the CTX-MSC group. Immunohistochemical studies in the CTX + MSCs and CTX + PreMSCs groups showed little evidence of TUNEL positivity compared with the CTX group. Moreover, the apoptotic index decreased in the CTX + PreMSCs group compared to the CTX + MSCs group. Moreover, CM-DiI-labeled MSCs in the ovary in the CTX + pre-MSCs group were higher than in the CTX + MSCs group.
Our experiment offers preconditioning as an effective strategy in stem cell therapy to potentiate MSCs' therapeutic efficacy in ovarian function failure.
将干细胞暴露于亚致死浓度的过氧化氢（HO）中可以预防氧化应激诱导的细胞凋亡。在本研究中，我们评估了 HO 预处理对人脐静脉脐带间充质干细胞（hUCV-MSCs）在卵巢早衰小鼠模型中的治疗潜力的影响。
成熟小鼠分为 4 组，每组 10 只。对照组（Ctrl）接受腹腔内（IP）磷酸盐缓冲盐水（PBS），CTX 组接受腹腔内注射环磷酰胺（CTX）。CTX 后接受单次静脉注射 CM-DiI 标记的 hUCV-MSCs 的 CTX+MSC 组，而 CTX 后接受 HO 预处理 MSC 的 CTX+preMSCs 组。7 天后，处死小鼠，取出卵巢进行组织学研究，如 H&E 染色和 TUNEL 检测。此外，计算不同卵巢区域中 CM-DiI 标记的 hUCV-MSCs 的数量。测量血清中的 FSH 和雌二醇值。
我们的研究表明，CTX 导致卵巢发生退行性改变和卵泡丢失。CTX+MSCs 和 CTX+preMSCs 组的卵泡数量明显高于 CTX 组。此外，在 CTX+preMSCs 组中，不同类型卵泡的数量高于 CTX-MSC 组。CTX+MSCs 和 CTX+preMSCs 组的免疫组织化学研究显示与 CTX 组相比，TUNEL 阳性的证据很少。此外，与 CTX+MSCs 组相比，CTX+preMSCs 组的凋亡指数降低。此外，CTX+preMSCs 组卵巢中 CM-DiI 标记的 MSCs 高于 CTX+MSCs 组。
我们的实验提供了预处理作为干细胞治疗的一种有效策略，以增强 MSCs 在卵巢功能衰竭中的治疗效果。
