Role and mechanisms of human embryonic stem cell-derived exosomes in promoting hair regeneration in cyclophosphamide-induced anagen hair loss mice
WANG Jintao
DANG Yuping
CAO Kaiyuan
WU Shuang
YANG Jingyuan
CAI Hong
Abstract：Objective To investigate the effect and potential mechanism of human embryonic stem cell-derived exosomes(ESC-Exos)on hair regeneration in cyclophosphamide-induced anagen hair loss mice mice.Methods ESC-Exos were isolated from the conditioned medium of human embryonic stem cells(ESCs)by ultra-high-speed centrifugation and identified.Forty-five specific pathogen-free(SPF)female C57BL/6 mice were equally divided into a blank group,a model group,and a treatment group.On day 0,hair removal was performed using heated paraffin and rosin(1:1 mixture).On day 9,the model and treatment groups were intraperitoneally injected with 120 mg/kg cyclophosphamide to induce anagen effluvium.After complete hair loss on day 14,the treatment group received multiple subcutaneous injections of 50 μg ESC-Exos per mouse(once every other day,3 times in total),while the blank and model groups were injected with an equal volume of normal saline.Back tissues of mice were collected on days 0,9,14,21,and 28.Hair follicle structural changes were evaluated by hair electron microscopy,hematoxylin-eosin(HE)staining,β-galactosidase staining,and immunofluorescence staining.Results Compared with the model group,the hair coverage rate and hair shaft diameter in the treatment group were significantly increased(P<0.05),with morphology approaching that of the blank group.HE and β-galactosidase staining showed that the number of hair follicles per unit area in the treatment group increased,the hair bulb structure was intact,and matrix cells were densely arranged.The senescence-associated β-galactosidase(SA-β-galactosidase)staining signal in the hair follicle bulge area was weakened,while the fluorescence signals of sonic hedgehog(SHH)and cytokeratin 15(CK15)were enhanced(P<0.05).Conclusion ESC-Exos can promote hair regeneration in cyclophosphamide-induced hair loss mice,and the mechanism may be related to SHH protein promoting hair follicle stem cell proliferation and inhibiting senescence.
Keywords：Hair lossCyclophosphamideExosomesHuman embryonic stem cellMiceModelanimal
Publication Date：2025-06-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：8( 161-167,189 )