Fig. 2

GnRH, TGF-β, and SHH affect the multiple functions of eMSCs, such as proliferation, differentiation, aging, and migration. GnRH inhibits the multiple beneficial functions of eMSCs, such as proliferation, differentiation, and migration, through the PI3K/AKT signaling. The activation of Akt signaling attenuates the GnRH-induced adverse effects on multiple stem cell functions. TGF-β inhibits the proliferation, differentiation, and colony-forming efficiency of SUSD2⁺ eMSCs. A83-01, TGF-β receptor inhibitor, can maintain the clonogenicity of SUSD2⁺ eMSCs, promote proliferation, prevent cell apoptosis, and maintain eMSC function. Exogenous SHH therapy could significantly alleviate various aging-related declines in multiple eMSC functions through the inhibition of SERPINB2 expression