Abstract

Cell therapy has been linked to an unexplained return of ovarian function and fertility in some cancer survivors. Studies modeling this in mice have shown that cells transplantation generates donor-derived oocytes in chemotherapy-treated recipients. This study was conducted to further clarify the impact of cell transplantation from different sources on female reproductive function after chemotherapy using a preclinical mouse model. Methods. Female mice were administered 7.5 mg/kg cisplatin followed by cell transplantation (one week later) using GFP+ female cell donors. For cell tracking, adipose derived stem cell GFP+ (ADSC), female germline stem cell GFP+/MVH+ (FGSC), or ovary cell suspension GFP+ mice were transplanted into cisplatin-treated wild-type recipients. After 7 or 14 days animals were killed and histological analysis, IHQ for GFP cells, and ELISA for estradiol were performed. Results. Histological examinations showed that ADSC, ovary cell suspension, and FGSC transplant increase the number of follicles with apparent normal structure in the cells recipient group euthanized on day 7. Cell tracking showed GFP+ samples 7 days after transplant. Conclusion. These data suggest that intraovarian injection of ADSCs and FGSC into mice with chemotherapy-induced ovarian failure diminished the damage caused by cisplatin.

Highlights

  • Premature ovarian failure is a syndrome characterized by lack of folliculogenesis and ovarian estrogen production, associated with amenorrhea and infertility in women under the age of 40 [1]

  • We investigated the restorative effects of adipose derived stem cell GFP+ (ADSC), female germline stem cell GFP+/MVH+ (FGSC), or ovary cell suspension on ovarian function

  • We believe that both cell types, ADSC and OS, have similar results based on the theory postulated by da Silva Meirelles et al in 2006 [14] claiming that the mesenchymal stem cells reside in all postnatal organs and tissues in a perivascular niche

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Summary

Introduction

Premature ovarian failure is a syndrome characterized by lack of folliculogenesis and ovarian estrogen production, associated with amenorrhea and infertility in women under the age of 40 [1]. One of the most devastating consequences of cancer treatment in the young female population is ovarian damage, resulting in diminished fertility potential [4]. The clinical application of adipose-derived stem cells (ADSCs) as treatment for intractable diseases or traumatic tissue damage has attracted attention. Another kind of adult stem cells, named female germline stem cells (FGSCs), that produce oocytes in vitro and fertilization-competent eggs in vivo has been identified in and isolated from adult mouse ovaries and has been tested in several researches [6, 7]. We investigated the restorative effects of ADSC, FGSC, or ovary cell suspension on ovarian function

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