Human adipose mesenchymal stemcells overexpressing dual chemotactic gene showed enhanced angiogenic capacity in ischaemic hindlimb model

Abstract

Aims In present study, we sought to characterize the angio-vasculogenic property of human adipose mesenchymal stem cells (ASCs) overexpressing dual chemokine GCP-2 and SDF-1a (ASC-G/S) and to determine the therapeutic potential of ASC-G/S in the context of experimental ischaemia. Methods and results We generated ASC-G/S line and performed flow cytometry, quantitative (q)-PCR, Matrigel tube formation, Matrigel plug assays, and in vivo therapeutic assays using hind limb ischaemia mouse model. Q-PCR results showed that the representative pro-angiogenic factors were highly upregulated in ASC-G/S compared with ASCs single chemokine overexpressing GCP-2 (ASC-G). In addition, ASC-G/S exhibited high expression of endothelium-specific genes shch as vWF and Flk-1 and showed robust in vitro micro-vascular formation. ASC-G/S was transplanted into ischaemic mouse hind limbs and compared with control groups. ASC-G/S injection prevented limb loss and augmented blood perfusion, suggesting that ASC-G/S enhances neovascularization in hind limb ischaemia. In addition, transplanted ASC-G/S revealed high vasculogenic potential in vivo compared with transplanted ASC-G. Conclusion Our data suggest that ASC-G/S has high therapeutic effects on hind limb ischaemia via robust angiogenic and vasculogenic action.