动员自体干细胞定向归巢原位修复骺板的研究

Application of tissue engineering in growth plate repair has a very broad future. However, lack of seed cells is still a significant barrier to define its clinical application. Recent studies have shown that autologous stem cells (ASCs) can be mobilized and migrated to injured site to repair the damage tissue. Our previous studies have suggested this can be modified as a new method for growth plate tissue engineering. In this research, we try to mobilize ASCs with G-CSF and/or SCF to recruit seed cells. A peptide sequence(H8) with highly specific affinity to bone marrow-derived stem cells (MSCs) is covalently conjugated to self-assembling peptide, which is loaded with SDF-1 and TGF-β3. The scaffold can release SDF-1 in a controlled way, and induce ASCs homing to the injured site, while H8 motif can selectively help MSCs adhere and proliferate. Released TGF-β3 can induce MSCs to differentiate in situ. Molecular biology, immunohistochemistry, animal model and so on are used to detect and analyze growth plate repair. Our research is expected to get growth plate functionally repaired in situ. And this work may not only reduce the demands for exogenous seed cells and cell culture in vitro, but also avoid ethic problems and transplantation complication.

组织工程的飞速发展为治疗骺板损伤带来了新的希望，但仍面临种子细胞缺乏的难题。近年来发现，组织损伤后，自体干细胞(ASCs)能够动员并向损伤组织归巢发挥修复作用，因此利用这一特性有望为骺板修复提供新的突破点。我们拟应用粒细胞集落刺激因子动员ASCs以募集种子细胞，构建含干细胞归巢肽H8模序的功能化自组装肽(FSAP)支架，并负载基质细胞衍生因子(SDF)-1与转化生长因子(TGF)-β3，通过控释SDF-1与TGF-β3介导干细胞归巢，利用H8模序诱导干细胞选择性粘附，在原位诱导分化对损伤骺板进行修复。采用分子生物学，生物力学，影像学等技术，观察ASCs动员归巢、分化修复骺板的可行性，并阐明其机制。本课题将有望通过注射FSAP实现动员ASCs对骺板损伤的原位生理性修复，避免了手术，无需进行体外细胞培养，减少对外源性细胞的需求及移植相关并发症，不涉及伦理问题，为骺板修复这一难题开辟一条新途径。

组织工程的飞速发展为治疗骺板损伤带来了新的希望，但仍面临种子细胞缺乏的难题。近年来发现，组织损伤后，自体干细胞(ASCs)能够动员并向损伤组织归巢发挥修复作用，因此利用这一特性有望为骺板修复提供新的突破点。在本课题中我们建立了粒细胞集落刺激因子（G-CSF）与干细胞因子（SCF）单独与联合应用对体内干细胞动员的动物模型，并进一步对G-CSF与SCF单独与联合应用对体内干细胞的的生物学作用，特点和规律进行了研究，确定了干细胞动员治疗的优化剂量，持续时间及时间窗。并对外周血细胞诱导横向分化为软骨细胞进行了研究。探讨了ASCs 动员归巢、分化修复骺板的可行性及其机制。本课题将有望通过实现动员ASCs 对骺板损伤的原位生理性修复，避免了手术，无需进行体外细胞培养，减少对外源性细胞的需求及移植相关并发症，不涉及伦理问题，为骺板修复这一难题开辟了一条新途径。