Insights into stem cell therapy for premature ovarian insufficiency

Hormone therapy, assisted reproductive technology, and regenerative medicine have been used to treat infertility due to premature ovarian insufficiency (POI), with limited success. It is timely to survey the field by outlining the controversies and promising prospects of evolving stem cell (SC) therapy for patients with POI. We first discuss several strategies of tissue-derived SC therapy and induced/engineered SC therapy and then enumerate mechanisms, including cellular regenerability induced in reproductive tissues and paracrine effects induced by various chemokines. Next, we evaluate the potential benefits of SC-based tissue engineering in reversing ovarian aging. Finally, we discuss the clinical feasibility of SC therapy and generalized regenerative medicine for the treatment of POI. In summary, SCs and SC-derived exosomes, induced pluripotent SCs, engineered SCs, and tissue engineering could start a new chapter for fertility rehabilitation in patients with POI. Uncovering the underlying molecular mechanisms and biological efficacy could be facilitated not only by animal experiments but also by security screening and clinical trials to validate SC-based therapy for POI.