Stroke is a significant unmet clinical need. The current stroke treatment of tissue plasminogen activator is limited to the very acute 4.5h after disease onset which benefits only less than 3% of ischemic stroke patients. Our overarching hypothesis advances the notion that gender, which has been established as a comorbidity factor of stroke, plays a key role in regenerative medicine, in particular stem cell therapy. We hypothesize that gender is a key factor in culture-induced stemness of adult stem cells. Our goal is to provide new evidence supporting gender effects on stroke and stem cells for the purpose of enhancing our understanding of the pathophysiology of the disease and developing novel stem cell-based therapeutics targeting gender-relevant stress hormones as manifested in a stroke-postpartum depression paradigm.