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

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.

Intra-ovarian injection of platelet-rich plasma into ovarian tissue promoted rejuvenation in the rat model of premature ovarian insufficiency and restored ovulation rate via angiogenesis modulation

“…Regarding the evaluation of fertility status after the PRP injection, the mating trial retrieved a significantly higher number of healthy litters in both PRP-treated groups compared to the non-treated ones. In agreement with our findings, and having stem cell infusion as the more recent gold standard [ 34 ], Mohamed and colleagues transplanted umbilical cord blood mesenchymal stem cells (UCMSCs) to POI mice, getting a higher number of born litters than in the untreated POI group [ 48 ]. Similar results were obtained as well from Lai and co-workers in 2014 and Su and colleagues in 2016, in where skin derived mesenchymal stem cells (SMSCs) and ADMSCs combined with collagen scaffold were used, respectively [ 8 , 49 ].…”

Human umbilical cord mesenchymal stem cells restore the ovarian metabolome and rescue premature ovarian insufficiency in mice

“…To date, some studies have indicated that MSCS transplantation can promote ovarian functional restoration in POI mice, as indicated by the recovery of body weight, ovarian weight, hormone levels, and ovarian reserve after stem cell therapy [ 21 , 23 , 32 – 43 ]. However, the mechanisms by which MSCs exert their actions have not been fully characterized.…”

Recent trends in stem cell therapy for premature ovarian insufficiency and its therapeutic potential: a review

“…UCMSCs interact with steroidal hormones by decreasing FSH levels and increasing AMH levels [32]. Treatment with UCMSCs recovers serum hormone levels, and although these levels are not completely within the normal range, they are better than those in the POI group.…”