Co-transplantation of Exosomes Derived from Hypoxia-preconditioned Adipose Mesenchymal Stem Cells Promotes Neovascularization and Graft Survival in Fat Grafting

Background: Adipose-derived stromal cells (ADSCs)-derived exosomes (ADSC-Exos) account for the proangiogenic potential of stem cell. This study aimed to investigate the effect of ADSC-derived exosomes (ADSC-Exos) on the survival in fat grafting.

Methods: A nude mouse model of subcutaneous fat grafting was adopted. Hypoxic preconditioned ADSC-Exos and ADSC-Exos were injected around the grafted tissue. The fat graft sample was weighed and examined by hematoxylin and eosin (H&E) staining and immunohistochemistry. Laser Doppler flowmetry and CD31 immunofluorescence staining were used to analyze neovascularization.

Results: ADSC-Exo and hypoxic ADSC-Exo groups had a significantly higher weight of fat graft and more perilipin-positive adipocytes than the control groups from 2 to 8 weeks after grafting, and the hypoxic ADSC-Exo group had better outcomes (all P < 0.05). H&E staining showed that ADSC-Exos attenuated infiltration of inflammatory cells around the fat grafts. Laser Doppler flowmetry showed that the two ADSC-Exo groups had better blood perfusion in the graft tissue than the control groups (all P < 0.05). Immunofluorescence demonstrated that the hypoxic ADSC-Exo group had significantly more CD31-positive cells than the ADSC-Exo group. In vitro study showed that hypoxic ADSC-Exos treatment significantly increased the migration (at 12 and 24 h) and in vitro capillary network formation (at 12 h) in the human umbilical vein endothelial cells (HUVECs) as compared with the ADSC-Exo group and control group (all P < 0.05).

Conclusions: Co-transplantation of ADSC-Exos can effectively promote the survival of graft, neovascularization and attenuated inflammation in the fat grafts. Hypoxia treatment can further enhance the beneficial effect of ADSC-Exos.