Umbilical Cord Blood Mesenchymal Stem Cells as an Infertility Treatment for Chemotherapy Induced Premature Ovarian Insufficiency.

Sara Mohamed,Amro Elsharoud,Lelyand Elam,Ayman Al-Hendy,Shahinaz Shalaby,Soumia Brakta

doi:10.3390/biomedicines7010007

Abstract

Background: Premature ovarian insufficiency (POI) is a challenging disease, with limited treatment options at the moment. Umbilical cord blood mesenchymal stem cells (UCMSCs) have demonstrated promising regenerative abilities in several diseases including POI. Materials and Method: A pre-clinical murine case versus vehicle control randomized study. Two experiments ran in parallel in each of the three groups. The first was to prove the ability of UCMSCs in restoring ovarian functions. The second was to prove improved fertility. A total of 36 mice were randomly assigned; 6 mice into each of 3 groups for two experiments. Group 1 (control), group 2 (sham chemotherapy), group 3 (stem cells). Results: In the first experiment, post-UCMSCs treatment (group 3) showed signs of restored ovarian function in the form of increased ovarian weight and estrogen-dependent organs (liver, uterus), increased follicular number, and a significant decrease in FSH serum levels (p < 0.05) compared to group 2, and anti-Mullerian hormone (AMH) serum levels increased (p < 0.05) in group 3 versus group 2. Immuno-histochemistry analysis demonstrated a higher expression of AMH, follicle stimulating hormone receptor (FSHR) and Inhibin A in the growing follicles of group 3 versus group 2. In the second experiment, post-UCMSCs treatment (group 3) pregnancy rates were higher than group 2, however, they were still lower than group 1. Conclusion: We demonstrated the ability of UCMSCs to restore fertility in female cancer survivors with POI and as another source of stem cells with therapeutic potentials.

Highlights

Premature ovarian failure (POF) recently known as premature ovarian insufficiency (POI) is a disease with a challenging nature and multiple complexities [1]
POF is classified by the World Health
We have recently reported that intra-ovarian administered bone marrow-derived mesenchymal stem cells (BMSCs) are able to restore ovarian hormone production and to reactivate folliculogenesis in the chemotherapy-induced ovarian failure mouse model [10]

Summary

Introduction

Premature ovarian failure (POF) recently known as premature ovarian insufficiency (POI) is a disease with a challenging nature and multiple complexities [1]. In 70% of POI cases, it is unlikely that a single specific cause can be identified. Many factors have been reported, including genetic, autoimmune, or prior anti-cancer treatment, either surgical, radiotherapy, or chemotherapy; in many cases, the cause remain unknown [4]. The incidence of other medical conditions increases as a result of decreased ovarian estrogen secretion, including Alzheimer’s, cardiovascular, autoimmune diseases, metabolic syndrome, osteoporosis, diabetes, and gynecological cancers [5]. Premature ovarian insufficiency (POI) is a challenging disease, with limited treatment options at the moment. Umbilical cord blood mesenchymal stem cells (UCMSCs) have demonstrated promising regenerative abilities in several diseases including POI. The first was to prove the ability of UCMSCs in restoring ovarian functions.

Methods

Results

Conclusion