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.

在人类脂肪干细胞 (hADSCs) 的临床移植中，必须使用蛋白水解酶处理来收集 hADSCs，但通常会导致细胞外基质 (ECMs) 互连的破坏。由于缺乏 ECMs 的 hADSCs 部分接收细胞信号，hADSCs 失活或经历细胞死亡。在此，我们提出了一种递送用新聚合物封装的富含 ECMs 的 hADSCs 的方法，用于移植到缺血伤口部位以增强治疗性血管生成功效。合成无酶 pH 敏感聚合物 (EFP) 并涂覆在组织培养板上用于 hADSCs 培养。当 hADSCs 在 EFP 包被的表面上培养时，它们很容易用 pH 6.0 的缓冲溶液分离，溶解的 EFP 用更多的 ECM 包裹 hADSCs 48 小时。当 ECMs 富集的 hADSCs 重新粘附时，在无血清和低氧细胞培养条件下，细胞分泌更多的血管生成因子。将富含 ECMs 的 hADSCs 注射到小鼠后肢缺血模型中时，血液灌注和血管再生率显着提高。与蛋白水解酶应用相比，我们使用 EFP 递送富含 ECM 的干细胞的方法显着改善了 hADSCs 的治疗性血管生成。