Application of extracellular vesicles from mesenchymal stem cells promotes hair growth by regulating human dermal cells and follicles

BACKGROUND

Dermal papillae (DP) and outer root sheath (ORS) cells play important roles in hair growth and regeneration by regulating the activity of hair follicle (HF) cells.

AIM

To investigate the effects of human mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs) on DP and ORS cells as well as HFs. EVs are known to regulate various cellular functions. However, the effects of hMSC-EVs on hair growth, particularly on human-derived HF cells (DP and ORS cells), and the possible mechanisms underlying these effects are unknown.

METHODS

hMSC-EVs were isolated and characterized using transmission electron microscopy, nanoparticle tracking analysis, western blotting, and flow cytometry. The activation of DP and ORS cells was analyzed using cellular proliferation, migration, western blotting, and real-time polymerase chain reaction. HF growth was evaluated ex vivo using human HFs.

RESULTS

Wnt3a is present in a class of hMSC-EVs and associated with the EV membrane. hMSC-EVs promote the proliferation of DP and ORS cells. Moreover, they translocate β-catenin into the nucleus of DP cells by increasing the expression of β-catenin target transcription factors (Axin2, EP2 and LEF1) in DP cells. Treatment with hMSC-EVs also promoted the migration of ORS cells and enhanced the expression of keratin (K) differentiation markers (K6, K16, K17, and K75) in ORS cells. Furthermore, treatment with hMSC-EVs increases hair shaft elongation in cultured human HFs.

CONCLUSION

These findings suggest that hMSC-EVs are potential candidates for further preclinical and clinical studies on hair loss treatment.

Key Words: Mesenchymal stem cells, Extracellular vesicles, Hair growth, Dermal papillae, Outer root sheath cells

Core Tip: Alopecia is a common medical problem affecting both males and females. This study found that Wnt3a is enriched in human mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs) and associated with their EVs’ surface. hMSC-EVs associated wnt3a can activate the Wnt/β-catenin signaling in recipient dermal papillae cells. hMSC-EVs activate keratin differentiation in recipient outer root sheath cells and increase hair shaft elongation. These findings open up for new hair growth treatment strategies to be developed for alopecia.

• Citation: Rajendran RL, Gangadaran P, Kwack MH, Oh JM, Hong CM, Sung YK, Lee J, Ahn BC. Application of extracellular vesicles from mesenchymal stem cells promotes hair growth by regulating human dermal cells and follicles. World J Stem Cells 2022; 14(7): 527-538
• URL: https://www.wjgnet.com/1948-0210/full/v14/i7/527.htm
• DOI: https://dx.doi.org/10.4252/wjsc.v14.i7.527