Wang Jiawei, Zhao Yunxiao, Zheng Fengque, Ma Nana, Qin Rongyan, Qin Weili, Liu Bo, Qin Aiping
Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, China.
Stem Cells Int. 2021 Oct 25;2021:8293699. doi: 10.1155/2021/8293699. eCollection 2021.
Saving the ovarian function of premature ovarian failure (POF) patients undergoing chemotherapy is an important problem in the field of reproductive medicine. At present, human umbilical cord mesenchymal stem cells (HucMSCs) have been used in the treatment of POF, but the effect is still not optimal. The purpose of this study was to determine whether human umbilical cord blood platelet-rich plasma (ucPRP) enhances the beneficial effects of HucMSCs in the treatment of POF. First, we observed the effects of changes in the biological activity of ucPRP on HucMSCs in vitro. Subsequently, we tracked the distribution and function of the HucMSCs in POF rats, and the rats' estrus cycle and serum sex hormones, follicular development, ovarian angiogenesis, ovarian granulosa cell proliferation, and apoptosis were assessed. The results of the study showed that the addition of ucPRP in vitro accelerates proliferation and reduces apoptosis of the HucMSCs while upregulating the stemness gene of the HucMSCs. The combined transplantation of HucMSCs and ucPRP resulted in more stem cells being retained in the ovaries of POF rats, the estrus cycle of the POF rats being restored, the levels of serum E2, AMH, and FSH improving, and damaged follicles beginning to grow. Finally, we confirmed that the potential mechanism of the combination of HucMSCs and ucPRP to rescue the ovarian function of POF rats is to promote ovarian angiogenesis and to promote the proliferation and reduce the apoptosis of ovarian granulosa cells. The upregulation of AMH and FHSR expression and the downregulation of caspase-3 expression in granulosa cells are potential mechanisms for the recovery of ovarian function. Our research results suggest that the combined application of HucMSCs and ucPRP is a safe and efficient transplantation program for the treatment of POF, thus providing a reliable experimental basis for the clinical application of stem cell therapy in POF.
挽救接受化疗的卵巢早衰（POF）患者的卵巢功能是生殖医学领域的一个重要问题。目前，人脐带间充质干细胞（HucMSCs）已被用于治疗POF，但效果仍不理想。本研究的目的是确定人脐带血富含血小板血浆（ucPRP）是否能增强HucMSCs治疗POF的有益效果。首先，我们观察了ucPRP生物活性变化对体外HucMSCs的影响。随后，我们追踪了POF大鼠体内HucMSCs的分布和功能，并评估了大鼠的发情周期、血清性激素、卵泡发育、卵巢血管生成、卵巢颗粒细胞增殖和凋亡情况。研究结果表明，体外添加ucPRP可加速HucMSCs的增殖并减少其凋亡，同时上调HucMSCs的干性基因。HucMSCs与ucPRP联合移植导致更多干细胞保留在POF大鼠的卵巢中，恢复了POF大鼠的发情周期，改善了血清E2、AMH和FSH水平，受损卵泡开始生长。最后，我们证实HucMSCs与ucPRP联合挽救POF大鼠卵巢功能的潜在机制是促进卵巢血管生成以及促进卵巢颗粒细胞增殖并减少其凋亡。颗粒细胞中AMH和FHSR表达上调以及caspase-3表达下调是卵巢功能恢复的潜在机制。我们的研究结果表明，HucMSCs与ucPRP联合应用是一种安全有效的治疗POF的移植方案，从而为干细胞疗法在POF临床应用提供了可靠的实验依据。
