组织工程化水凝胶促进间充质干细胞修复脑梗死的MRI分子成像研究

Mesenchymal stem cells (MSCs) -based therapy is the most promising therapeutic strategy for the treatment of cerebral infarction. However, the retention rate and survival rate of MSCs transplantation were low. Thus, how to improve the retention rate and survival rate of transplanted stem cells as well as improve their therapeutic effect are urgent problems in stem cells-based therapy. Based on our previous studies, in this study, we will design an injectable thermosensitive HA-F127-based hydrogel, activate this hydrogel with NT-3 and VEGF trophic factors, and then combine it with MSCs to synthesize a tissue-engineered scaffold. Additionally, the retention rate and survival rate of MSCs after the tissue-engineered scaffold implanted will be in vivo dynamically monitored by using the FerritinH-based MR reporter gene imaging, and the effect of tissue-engineered scaffold on the structure and neurological function of cerebral infarction will be observed, to clarify whether the tissue-engineered hydrogel can improve the retention and survival rate of MSCs after transplantation and repair the cerebral infarction. In light of the multidisciplinary integration of molecular MR imaging, tissue engineering and molecular biology, the aim of this project is to establish a new method to in vivo accurately monitor the transplanted MSCs in the tissue-engineered scaffold and to explore new ways and new means to improve the neural repair effect of stem cells-based therapy in cerebral infarction, thus to promote the clinical transformation of stem cells-based therapy.

间充质干细胞（MSCs）移植是脑梗死目前最具运用前景的新治疗策略，然而MSCs移植后的滞留率及存活率均低，如何提高移植干细胞的滞留率及存活率，提高其治疗效果是亟待解决的问题。本研究拟在前期研究基础上，制备基于HA-F127的可注射性温敏水凝胶，以NT-3及VEGF营养因子活化水凝胶，再复合MSCs制备组织工程化支架，建立脑梗死动物模型，进行组织工程化支架的移植治疗脑梗死，利用基于FerritinH的MRI报告基因手段，活体动态检测组织工程化支架移植后MSCs的滞留率及存活率，观察组织工程化的支架移植对脑梗死结构及神经功能的恢复情况，明确组织工程化水凝胶能否提高MSCs移植后的局部滞留及存活率及修复脑梗死能力。通过MRI分子影像学、组织工程学、分子生物学等多学科交叉融合，建立组织工程化支架中MSCs的活体示踪技术，探索提高干细胞治疗脑梗死疗效的新手段和新方法，有助于推动干细胞治疗的临床转化。

间充质干细胞（MSCs）移植是脑梗死目前最具运用前景的新治疗策略，然而MSCs移植后的滞留率及存活率均低，如何提高移植干细胞的滞留率及存活率，提高其治疗效果是亟待解决的问题。本研究在前期研究基础上，成功制备基于HA-F127的可注射性温敏水凝胶，其具有良好的物理特性，以NT-3及VEGF营养因子活化水凝胶，再复合PLL-SPIO磁性标记的MSCs制备组织工程化支架，体外结果表明PLL-SPIO能够高效、安全地标记MSCs，复合标记MSCs及神经营养因子的水凝胶具有良好的生物相容性。动物实验中，建立脑梗死动物模型，移植上述组织工程化支架治疗脑梗死，MRI能够活体动态检测组织工程化支架移植后MSCs的滞留率及存活率，MRI活体显示时间长达6周。MRI脑梗死体积、功神经功能评分及组织病理学结果均表明组织工程化的支架移植能够明显促进脑梗死结构及神经功能的恢复，能够明显促进脑梗死的修复。本项目通过MRI分子影像学、组织工程学、分子生物学等多学科交叉融合，建立了组织工程化支架中MSCs的活体示踪技术，寻找了提高干细胞治疗脑梗死疗效的新手段和新方法，有助于推动干细胞治疗的临床转化。