以细胞治疗为代表的再生医学为治愈包括缺血性疾病在内的诸多疑难病症带来了希望.目前细胞治疗最大的挑战之一是植入细胞的存活率和功能不甚理想。导致需要注射大量细胞，同时大多数细胞游离到非病灶区产生潜在副作用。移植细胞受损主要是因为脱离了适于其生长和功能维持的微环境。因此对于调控细胞存活和功能的微环境进行系统性探究和优化将对其临床应用具有重要价值。本研究将整合微组织工程和组织脱细胞化以获得能够增强间充值干细胞（MSCs）促血管再生的人工微环境，从而应对上述挑战。将基于前期开发的3D微组织阵列和可注射3D微组织技术，并结合组织脱细胞方法高通量筛选促血管化3D微环境并系统探究脱细胞血管组织人工微环境如何调控MSCs表型和功能。最终这种经过筛选优化的促血管化3D微环境可注射到下肢缺血小鼠模型中改善传统游离细胞注射疗法的定位和存活率，实现高效治疗。本计划对于探究和优化其他细胞微环境和再生治疗同样极具价值。

Regenerative medicine as being represented by cell therapy has brought hope for treatment of many incurable diseases including ischemic diseases. One of the biggest challenges of cell therapy is that the survival and function of transplanted cells cannot be well-maintained. This results in administration of a large number of cells, while the majority of the cells diffuse to non-lesion areas potentially causing adverse side effects. Damage of the transplanted cells is mainly due to lack of suitable cellular microenvironment for maintaining their growth and function. Therefore, systematic exploration and optimization for the cellular micro-environment will be vital to regulate cell survival and function and ultimate clinical applications. In this study, micro-tissue engineering and decellularization technology will be integrated to obtain artificial pro-angiogenesis cellular micro-environment for enhanced stem cell (e.g. MSCs) function which potentially can address the above-mentioned challenges. Previously developed 3D microtissue array and injectable 3D microtissue technologies combined with decellularization method will be used for high throughput screening of pro-angiogenesis 3D microenvironment and systematically explore how the artificial decellularized vascular microenvironment regulate MSCs phenotype and function. Eventually, the optimized in vitro angiogenic microenvironment can be injected into the limb ischemic mouse model to improve the positioning, survival and treatment efficiency of traditional free cell injection-based therapy. The strategy used in this proposal is equally valuable for optimization of the micro-environment and regenerative treatment of other types of cells.