Oxidative stress activates the transplanted adipose-derived stem cells to exert antioxidant effects in alopecia treatment.

Background: Alopecia is a global dermatological challenge. Adipose-derived stem cells (ADSC) show therapeutic potential, but their mechanisms in promoting hair regrowth, particularly under oxidative stress conditions, remain unclear..

Objective: To investigate ADSC's role in promoting hair regrowth by mitigating oxidative stress.

Methods: Using H₂O₂-stressed HaCaT cells, ADSC's protective effects were evaluated via conditioned medium (CM) and co-culture. Assessments included cell viability, colony formation, ROS, MDA, antioxidant enzymes, and 8-OHdG. Nrf2 activation was analyzed by immunofluorescence and Western blot. A mouse radiation injury model validated findings.

Results: Non-pretreated ADSC offered limited oxidative protection to HaCaT cells. Conversely, H₂O₂-pretreated ADSC significantly enhanced HaCaT viability and proliferation in both CM and co-culture systems. This involved paracrine activation of the Nrf2 pathway in HaCaT cells, boosting antioxidant enzymes, accelerating ROS clearance, and reducing lipid peroxidation. These effects were reversible with Nrf2 inhibition. In vivo, CM from H₂O₂-stimulated ADSC promoted hair regrowth in irradiated mice, outperforming CM from non-pretreated ADSC by activating Nrf2 and reducing tissue oxidative damage.

Conclusions: Oxidative stress potentiates the protective capacity of ADSC against oxidative via Nrf2-dependent paracrine mechanisms, offering a promising strategy for alopecia treatment.