Fibrin Facilitates Mesenchymal Stem Cells to Ameliorate Rats with Polycystic Ovary Syndrome

Yuanyuan Li,Yixun Liu,Jia Guo,Shoulong Deng,Qi Gu,Zili Gao

doi:10.3390/app10103598

Abstract

Polycystic ovarian syndrome (PCOS) is a ubiquitous hormonal disorder and induces female infertility and heterogeneous syndromes, for which there is still no effective treatment. Thanks to the properties of immunomodulatory and endocrine regulation, mesenchymal stem cells (MSCs) have been widely used in various disease types. There were few reports for MSCs injected to ovaries due to the size limitation and complicated vascular network. Here, we develop one simple and efficient approach to deliver and stabilize MSCs in the outside of the ovary without blood leaking through the fibrin gelation, which also possesses excellent biocompatibility to support MSC survival. Notably, the transplantation of MSCs, encapsulated in fibrin hydrogel, could rescue ovarian function more efficiently compared to only MSC control in terms of elevated estradiol (E2) and progesterone (P) levels, diminished gonadotropins (LH/FSH), testosterone (T), and transforming growth factor-β1 (TGF-β1) levels, regular estrous cycles, enhanced number of granulosa cells, and reduced number of immature cystic follicles. The size and weight of the ovary increased for MSCs both within and without fibrin in PCOS rat models in two weeks. Moreover, we have shown the versatility of fibrin hydrogel as a cell-compatible platform for advanced stem cell translation, including identifying novel mechanisms of cell survival support, tissue development, and regenerative medicine.

Highlights

Polycystic ovarian syndrome (PCOS) is a complicated endocrine disease occurring in 6–7% of reproductive-age women [1], which affects patients’ health by increasing the risk of cardiac disease, obesity, insulin resistance, and infertility [2]
The primary finding of this study is that UC-mesenchymal stem cells (MSCs) within fibrin hydrogel have shown therapeutic potential by restoring ovarian function and structure in PCOS rats
Our results reveal that direct injection of umbilical cord MSCs (UC-MSCs) alone as well as with fibrin scaffolds elevate serum estradiol and progesterone levels, whereas they significantly decrease gonadotropin (LH/FSH), testosterone, and transforming growth factor-β1 (TGF-β1) levels

Summary

Introduction

Polycystic ovarian syndrome (PCOS) is a complicated endocrine disease occurring in 6–7% of reproductive-age women [1], which affects patients’ health by increasing the risk of cardiac disease, obesity, insulin resistance, and infertility [2]. The pathogenesis of PCOS has not been well elucidated, it has been reported to be a multifactorial disease that involves genetic and environmental factors [1,3,4]. Excessive gonadotropin (LH/FSH) and androgen (T) levels affect ovarian function along with increasing transforming growth factor-β1 (TGF-β1) levels and enhancing apoptosis of granulosa cells, in which case, many immature cystic follicles form in the ovaries of PCOS patients [5,6,7]. Different kinds of therapies are used for the treatment of PCOS such as weight management, medicines targeting insulin resistance, or hormonal drugs [8].

Objectives

Methods

Findings

Conclusion