Activated Human Umbilical Cord Blood Platelet-Rich Plasma Enhances the Beneficial Effects of Human Umbilical Cord Mesenchymal Stem Cells in Chemotherapy-Induced POF Rats.

Jiawei Wang,Aiping Qin,Bo Liu,Rongyan Qin,Yunxiao Zhao,Fengque Zheng,Nana Ma,Weili Qin,Diana Klein

doi:10.1155/2021/8293699

Abstract

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.

Highlights

Premature ovarian failure (POF) is clinically defined as decreased ovarian function in young women and mainly manifests as abnormal menstruation, abnormal increase in FSH, decreased estrogen fluctuations, and even infertility [1]
Red fat droplets stained with Oil Red O observed in human umbilical cord mesenchymal stem cells (HucMSCs) were induced by adipogenesis (Figure 1(g))
Our results suggest that the addition of umbilical cord blood platelet-rich plasma (ucPRP) allows a greater number of HucMSCs to be retained in the body

Summary

Introduction

Premature ovarian failure (POF) is clinically defined as decreased ovarian function in young women and mainly manifests as abnormal menstruation, abnormal increase in FSH, decreased estrogen fluctuations, and even infertility [1]. Restoring the ovarian function in young women undergoing chemotherapy with an associated loss of fertility is a problem that urgently needs to be solved. There are many methods for the treatment of POF: hormone replacement therapy (HRT), immunomodulation therapy, and ovarian tissue cryopreservation. These treatments have certain limitations, including increased risk of breast or ovarian cancer, fatal allergic reactions, complicated surgical procedures, and inability to promote damaged ovarian tissue regeneration [3,4,5]

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