ApoEVs promote hair regeneration. (A, B) C57BL/6 mice in the telogen phase (7 weeks old) were depilated. PBS, apoEVs (4 × 106) or MSCs (1 × 106) were subcutaneously injected into the dorsal skin. Minoxidil (1%) was topically applied daily to the dorsal skin as a positive control. Representative photos of mice showing skin color darkness and hair regrowth at 0, 7, 10 and 14 days post-injection. The level of pigmentation was quantified by the intensity of the darkness of the back skin in the same area. n = 3. *P < 0.05, **P < 0.01, ***P < 0.001, one-way ANOVA test. ns: not significant. Data shown as mean ± SD. (C) Immunohistochemistry staining shows the expression level of active-β-catenin in hair follicle from control, apoEV, MSC and minoxidil groups. (D, E) Representative photos of mice showing skin color darkness and hair regrowth after intervention at 0, 7, 10 and 14 days post-injection. The level of pigmentation was quantified by the intensity of the darkness of the back skin in the same area. n = 3. *P < 0.05, ***P < 0.001, one-way ANOVA test. ns: not significant. Data shown as mean ± SD. (F) Immunofluorescent images show that LiCl treatment increased the accumulation of PKH26-ApoEV in dermal papilla to promote the hair regeneration, but XAV939 treatment inhibited the accumulation of PKH26- ApoEV in dermal papilla to slow the regrowth process. White dotted line indicated the area of DP. The relative mean intensity of apoEVs around DP were calculated. n = 3. **P < 0.01, ***P < 0.001, one-way ANOVA test. Data shown as mean ± SD. DP, dermal papilla. Scale bar (C), 100 μm; Scale bar (F), 20 μm.