In Vitro Differentiation of Bone Marrow Mesenchymal Stem Cells into Human Male Gametes
Abstract
Islam Al Dababsekh, Yurii Lesniak, Natalia Oleksenko and Amina Al Dababsekh
Introduction: Male infertility is a growing global health concern, contributing to nearly half of all infertility cases, with conditions such as azoospermia presenting significant therapeutic challenges. Conventional treatments offer limited solutions, particularly for absolute infertility. The emergence of regenerative medicine, especially mesenchymal stem cell (MSC) therapy, offers new possibilities. This study investigates the feasibility of differentiating human bone marrow-derived MSCs into functional spermatocytes in vitro, presenting a potential alternative for patients lacking viable gametes.
Materials and Methods: MSCs were mobilized using granulocyte colony-stimulating factor (G-CSF), isolated from peripheral blood, and cultured under a simulated germline environment. Key markers such as Oct-4, DAZL, and DMC1 were used to confirm stemness and meiotic progression. Gamete maturation was tracked over 75 days, and fertilization competence was assessed via in vitro fertilization (IVF) with donor oocytes.
Results: MSCs successfully differentiated into spermatocyte-like cells displaying structural and functional markers of spermatogenesis, including acrosome development and partial motility. IVF trials resulted in the fertilization of 14 oocytes and the development of 14 viable morula-stage embryos, all of which were cryopreserved. This demonstrates the potential of MSC-derived gametes in restoring fertility in azoospermic individuals.
Conclusion: This study offers strong proof-of-concept for the use of MSCs in in vitro gametogenesis as a treatment for absolute male infertility. While clinical application requires further validation, this approach presents a promising shift in infertility therapy—from assisted reproduction toward functional reproductive restoration. Future directions may also extend to female infertility and broader regenerative applications in reproductive medicine.