生物活性载体材料调控干细胞和组织微环境治疗急性肾损伤

急性肾损伤是严重的临床综合征，目前缺乏有效的治疗手段。本项目将针对急性肾损伤的病理机制和发病进程，拟利用干细胞和生物活性材料调控损伤微环境，激活肾组织内源性的修复潜能，增强生理性修复，抑制病理性修复，减轻肾脏纤维化。拟制备多种生物活性载体材料，包括可注射活性水凝胶和多功能纳米材料。载体在体外调控间充质干细胞的旁分泌功能，和作为干细胞局部注射移植的载体；纳米载体材料通过静脉输入，靶向归巢损伤组织，释放活性分子，调控肾脏组织微环境。以载体材料为核心，从三个层面研究急性肾损伤的修复与机制：1）载体材料改善移植干细胞的驻留和存活率，调控其旁分泌和分化；2）载体材料释放活性分子激活内源性干细胞及其它组织自修复潜能；3）载体材料调控肾组织微环境，抑制或逆转成纤维细胞表型，减轻肾脏纤维化，延缓组织重塑。科学问题来自临床，研究思路和手段紧密结合临床实际，以期为急性肾损伤的临床治疗提供新的有效手段。

Acute kidney injury is a serious clinical challenge that currently lacks effective treatment. This project will address the pathogenesis and pathological mechanisms of acute kidney injury through investigating the use of stem cells in combination with bioactive materials for kidney repair. This project aims to regulate the microenvironment of damaged kidney tissue, activate the endogenous repair potential of renal tissue, whilst inhibiting pathological progression and reducing renal fibrosis; to restore physiological kidney function. A variety of carrier materials will be prepared and utilised, including injectable bioactive hydrogels and multifunctional nanocarrier materials. We will assess biomaterial regulatory effects on paracrine function of mesenchymal stem cells in vitro, and determine their suitability to serve as carriers for the local injection of stem cells. The nanocarrier materials will be designed for targeted-delivery by intravenous injection to the damaged kidney tissue, to release bioactive molecules and regulate the tissue and cell microenvironment. The potential for carrier materials to promote kidney repair and the elucidation of mechanisms of acute kidney injury will be studied at three levels. This will be through the assessment of whether the carrier material can: 1) Improve the survival rate of resident and transplanted stem cells, and if it can regulate their paracrine activity and differentiation lineage; 2) Provide sustained release of bioactive molecules to stimulate the endogenous self-repair potential of stem cells and the cells from the surrounding resident tissue; 3) Regulate the renal microenvironment, inhibit or reverse the myofibroblast phenotype to reduce renal fibrosis, and promote tissue remodelling and restoration of healthy tissue. In order to address this clinical challenge, this research project will explore the research ideas, methods and technology for integration into clinical practice and the development of new and effective therapeutic treatments for acute kidney injury.