特络细胞与肾小管生发前体细胞胞间对话在急性肾损伤修复中的作用和机制

Cell resources and mechanisms involved in the process of acute renal injury reparation are still unclear. Telocyte, a special cell with unique morphology and phenotype, has been unveiled in many organs, such as heart, skeletal muscle and skin. In 2012, we reported the existence in human renal cortex for the first time in worldwide. We successfully defined the morphologic characteristics and secretion function which indicated that telocyte could be a potential stem cell supporting cell. Furthermore, we found that infusion of renal telocytes into rats suffering acute renal injury were able to reduce the ischemia/reperfusion injury and preserve the renal function, which were dependent on the growth factor releasing effect in vivo. This phenomenon verified our speculation to a solider degree. Meanwhile, other researches proved that telocytes, as supporting cells, were located in myocardium stem cell niches, protecting myocardium cells from injury. On the other hand, previous studies have confirmed that CD24+CD133+CD106- tubular progenitor cells with the capability of self-renewal and pluripotent differentiation were potential renal stem cells. Based on our former work and subsistent foundings, we plan to verify whether telocytes can promote the proliferation and tubular lineage committed differentiation of CD24+CD133+CD106- renal progenitor cells in vivo or ex vivo, and explore the key molecular participating in the cross-talk between telocyte and renal progenitor cell utilizing proteinogram. The program is aimed to provide new approaches andstrategies for acute renal injury.

急性肾损伤修复的细胞来源及机制尚未明确。特络细胞（Telocyte, TC）是新近发现的一种形态、表型独特的细胞，广泛分布于心、骨骼肌、皮肤等器官中。我们于2012年率先发现并报道了肾脏特络细胞，描述了其形态特征和分泌功能，推测其可能为干细胞孵育细胞。随后我们发现过继输注肾脏特络细胞，可减轻肾脏缺血再灌注损伤，保护肾功能，且其作用途径依赖于体内条件下生长因子的释放，进一步验证了我们的推测。与此同时，其他研究也表明，心脏中的特络细胞存在于心肌干细胞龛中，发挥孵育功能，修复心肌损伤。研究表明，肾脏CD24+CD133+CD106-肾小管生发前体细胞具备自我更新和多向分化能力，是肾脏内源性干细胞。本项目拟在前期研究基础上，通过体内外试验，观察特络细胞能否促进肾小管生发前体细胞的增殖及向肾小管上皮细胞定向分化；并进一步通过蛋白谱研究，探讨两者之间对话的关键分子，为急性肾损伤修复提供新的思路和策略。

特络细胞（Telocyte, TC）是新近发现的一种形态、表型独特的细胞，广泛分布于心、骨骼肌、皮肤等器官中。我们于2012年率先发现并报道了肾脏特络细胞，描述了其形态特征和分泌功能，推测其可能为干细胞孵育细胞。本项目在前期工作的基础上，通过CD34、CD117及vimentin三阳性指标法筛选、获得了高纯度的人类肾脏特络细胞。通过对人肾脏特络细胞单细胞转录组测序，我们阐明了人类肾脏特络细胞的特性、功能及与其他多种类型的细胞的关系。我们进一步将特络细胞尾静脉注射于肾纤维化模型的大鼠中，发现特络细胞能够减轻大鼠肾纤维化，并且这一作用可能是通过间接提高肝细胞生长因子（Hepatocyte growth factor，HGF）的方式实现。通过目前所得结果，本项目得到了高效收集人类原代肾脏特络细胞的方法，阐明了特络细胞的诸多特性，可为后续研究肾脏特络细胞的功能与作用奠定良好的实验基础以及为进一步临床转化提供可靠的理论依据。