Delivery of extracellular matrix-enriched stem cells encapsulated with enzyme-free pH-sensitive polymer for enhancing therapeutic angiogenesis

At clinical transplantation of human adipose derived stem cells (hADSCs), a proteolytic enzyme treatment for harvesting hADSCs must be used but usually causes the disruption of extracellular matrices (ECMs) interconnection. As ECMs-poor hADSCs partially receive the cellular signals, hADSCs deactivated or undergo cell death. Herein, we have proposed a method for delivering ECMs-enriched hADSCs encapsulated with a new polymer for transplanting into ischemic wound sites to enhance the therapeutic angiogenic efficacy. Enzyme free pH-sensitive polymer (EFP) was synthesized and coated on tissue culture plate for hADSCs culture. When the hADSCs were cultured on EFP-coated surfaces, they were easily detached with pH 6.0 buffer solution and dissolved EFP wrapped hADSCs with more ECMs for 48 h. When ECMs enriched-hADSCs were re-adhered, the cells secreted more angiogenic factors under serum free and hypoxic cell culture condition. When injecting ECMs-enriched hADSCs to mouse hindlimb ischemia models, the blood perfusion and blood vessel regeneration rate were significantly higher. Our method for delivering ECMs-enriched stem cells using EFP significantly improved the therapeutic angiogenesis with hADSCs compared to proteolytic enzymatic application.