Fertility rescue and ovarian follicle growth promotion by bone marrow stem cell infusion.

OBJECTIVE

To assess if infusion of human bone marrow-derived stem cells (BMDSCs) could promote follicle development in patients with impaired ovarian functions.

DESIGN

Experimental design.

SETTING

University research laboratories.

ANIMAL(S): Immunodeficient NOD/SCID female mice.

INTERVENTION(S): Human BMDSCs were injected into mice with chemotherapy-induced ovarian damage and into immunodeficient mice xenografted with human cortex from poor-responder patients (PRs).

MAIN OUTCOME MEASURE(S): Follicle development, ovulation, and offspring. Apoptosis, proliferation, and vascularization were evaluated in mouse and human ovarian stroma.

RESULT(S): Fertility rescue and spontaneous pregnancies were achieved in mice ovaries mimicking PRs and ovarian insufficiency, induced by chemotherapy, after BMDSC infusion. Furthermore, BMDSC treatment resulted in production of higher numbers of preovulatory follicles, metaphase II oocytes, 2-cell embryos, and healthy pups. Stem cells promoted ovarian vascularization and cell proliferation, along with reduced apoptosis. In xenografted human ovarian tissues from PRs, infusion of BMDSCs and their CD133+ fraction led to their engraftment close to follicles, resulting in promotion of follicular growth, increases in E secretion, and enhanced local vascularization.

CONCLUSION(S): Our results raised the possibility that promoting ovarian angiogenesis by BMDSC infusion could be an alternative approach to improve follicular development in women with impaired ovarian function.

CLINICAL TRIAL REGISTRATION NUMBER

NCT02240342.