Consideration of biological sex in stem cell therapies

Regenerative cell therapies have emerged as the next major development in medicine. Stem cell therapies are defined as any treatment utilizing viable human stem cells including adult stem cells, embryonic stem cells, and induced pluripotent stem cells. Their ability to self-renew and potential to differentiate into multiple cell types has led to numerous clinical trials which aim to establish among other indications their safety and efficacy in tissue regeneration, immune modulation, and cancer therapy. The challenges surrounding commercial viability and the clinical use of novel therapies are associated with difficulties in establishing clinical utility and cost-effectiveness. Only recently has sex and gender bias been identified as a potentially critical pitfall in translational research. Future therapeutic strategies utilizing stem cells should be based on research that has considered sex as a biological variable throughout the biomedical development spectrum in order to maximize positive outcomes and avoid the potential consequences associated with such bias. In this review, we focus on the implications that biological sex may have on translational regenerative stem cell therapies and consider the limitations of the present body of knowledge.