水凝胶载体移植造血干细胞治疗心肌梗死的新方法

Hematopoietic stem cells (HSCs) transplantation is an effective treatment for myocardial infarction and other ischemic diseases. However, the stems cells tend to lose soon after transplantation, which hinder the application of cell therapy of myocardial infarction. In order to enhance the implantation and survival of stem cells, our previous studies have found that the thermosensitive hydrogel could act as a cell carrier with a temperature-controlled character and conformational plasticity, to prevent the short-term lost of the transplanted cells. Thus, we propose the possibility of using thermosensitive hydrogel as a cell carrier to transplant HSCs to the infarct myocardium. In addition, we have found that using stromal-free culture expand substantial HSCs, and genetically modifying HSCs can promote their survival and differentiation. But its efficacy in myocardial infarction is not yet clear. Therefore, in this project we will synthesize thermosensitive hydrogel to encapsulate HSCs or genetically modified HSCs, then transplant it into animal infarct heart. We will observe the the implantation, survival and differentiation of HSCs, and assess myocardial repair and angiogenesis, in order that we can evaluate the efficacy of using hydrogel to transplant HSCs to infarct heart, and provide new ideas and experimental evidence for stem cell therapy of myocardial infarction.

造血干细胞（Hematopoietic stem cells, HSCs）移植是治疗心肌梗死等缺血性疾病的有效措施。干细胞移植后往往在短期损失，是干细胞移植疗法急需解决的问题。为了促进干细胞的植入与存活，我们前期研究发现，温敏性水凝胶作为细胞载体具备温度可控性、构型可塑性等优势，能防止移植细胞短期损失。因此，我们提出使用温敏性水凝胶作为载体移植HSCs到梗死心肌的可能性。我们也发现使用无基质培养法能扩增足够的供体HSCs，在移植前基因修饰的HSCs可促进其存活和分化，但是，其在心肌梗死中的疗效尚未明确。本项目拟合成温敏性水凝胶，封装HSCs或基因修饰的HSCs，移植到动物梗死心肌，观察HSCs的植入、存活和分化能力，并评估心肌修复与血管生成情况，探讨水凝胶载体移植HSCs治疗心肌梗死的疗效，为心肌梗死的干细胞疗法提供新的思路和实验依据。

本项目使用合成温敏性水凝胶，封装HSCs或基因修饰的HSCs，移植到动物梗死心肌，观察HSCs的植入、存活和分化能力，并评估心肌修复与血管生成情况，系统探讨水凝胶载体移植HSCs治疗心肌梗死的疗效，为心肌梗死的干细胞疗法提供新的思路和实验依据。本研究结果首次明确球形TiO2 NPs能够在生物相容性PG/CTS水凝胶分子网络表面上均匀分布并稳定交联，合成的纳米复合水凝胶呈现出压缩模量的增加，以及具备良好溶胀特性。基于此，进一步明确了TiO2 NPs官能化的PG/CTS复合水凝胶能够作为心肌组织修复与再生研究的高分子生物材料载体，其控制释放机理可辅助增强MIRI心脏中的HSCs促进心肌修复和改善心功能作用。概括而言，本研究相关的效应与机制探讨为TiO2 NPs复合PG/CTS的水凝胶可作为心脏修复的HSC疗法研究与应用的合适ECM材料及递送载体提供新颖的科学依据，也为同类策略的纵深研究思路提供崭新的科学与技术参考。