Human embryonic stem cells-derived endothelial cell therapy facilitates kidney regeneration by stimulating renal resident stem cell proliferation in acute kidney injury
Human embryonic stem cells-derived endothelial cell therapy facilitates kidney regeneration by stimulating renal resident stem cell proliferation in acute kidney injury
复制标题
人胚胎干细胞衍生的内皮细胞疗法通过刺激急性肾损伤中的肾常驻干细胞增殖来促进肾脏再生
DOI：
10.1007/s11434-013-5890-3
复制
发表时间：
2013-06
影响因子：
--
通讯作者：
Zongjin Li
中科院分区：
文献类型：
--
作者：
Deling Kong;He Lu;Chen Li;Guowei Feng;Lina Mao;Tingyu Ke;Yongzhe Che;Yong Xu;Zongjin Li
内皮细胞治疗已被认为可以促进缺血肾脏的组织再生和血管化。然而，还没有发表的研究检查内皮细胞治疗在肾脏恢复中的直接作用。本研究调查了内皮细胞在急性肾损伤（阿基）小鼠模型中的治疗功效。因此，人胚胎干细胞衍生的内皮细胞（hESC-ECs）标记的报告系统编码的萤火虫荧光素酶（Fluc）和绿色荧光蛋白（GFP）的双融合报告基因，其特征在于Fluc成像和免疫荧光染色。将培养的hESC-ECs（1×106）注射到阿基后不久的缺血肾中。在内皮细胞移植后第1天至第14天，在体内监测移植的hESC-EC的存活，并通过组织学分析评估hESC-EC治疗对肾再生的潜在影响。我们报告说，一个相当大的水平的生物发光活性检测hESC-EC注射后24小时，随后从1至14天逐渐下降。人ESC-ECs显着加速肾细胞增殖响应缺血诱导的损伤，表示BrdU+细胞的数量增加。肾干细胞增殖标记物Sca-1和BrdU的共表达进一步表明，观察到的肾细胞再生刺激至少部分是由于肾常驻干细胞增殖增加，特别是在髓索和小动脉内。在肾恢复的早期阶段也观察到hESC-ECs向平滑肌细胞的分化。总之，我们的研究结果表明，内皮细胞治疗通过促进阿基中的血管形成、转分化和内源性肾干细胞增殖来促进肾脏恢复。
Endothelial cell therapy has been implicated to enhance tissue regeneration and vascularization in ischemic kidney. However, no published study has yet examined direct effects of endothelial cell treatment in kidney recovery. This study investigated the therapeutic efficacy of endothelial cells in a mouse model with acute kidney injury (AKI). Thus, human embryonic stem cells-derived endothelial cells (hESC-ECs) labeled with a reporter system encoding a double fusion reporter gene for firefly luciferase (Fluc) and green fluorescent protein (GFP) were characterized by Fluc imaging and immunofluoresence staining. Cultured hESC-ECs (1×106) were injected into ischemic kidney shortly after AKI. Survival of the transplanted hESC-ECs was monitored in vivo from day 1 to 14 after endothelial cell transplantation and potential impact of hESC-EC treatment on renal regeneration was assessed by histological analyses. We report that a substantial level of bioluminescence activity was detected 24 h after hESC-EC injection followed by a gradual decline from 1 to 14 d. Human ESC-ECs markedly accelerated kidney cell proliferation in response to ischaemia-induced damage, indicated by an elevated number of BrdU+ cells. Co-expression of Sca-1, a kidney stem cell proliferation marker, and BrdU further suggested that the observed stimulation in renal cell regeneration was, at least in part, due to increased proliferation of renal resident stem cells especially within the medullary cords and arteriole. Differentiation of hESC-ECs to smooth muscle cells was also observed at an early stage of kidney recovery. In summary, our results suggest that endothelial cell therapy facilitates kidney recovery by promoting vascularization, trans-differentiation and endogenous renal stem cell proliferation in AKI.
登录
查看更多内容
影响因子：
24
作者：
Li, Zongjin;Lee, Andrew;Huang, Mei;Chun, Hyung;Chung, Jaehoon;Chu, Pauline;Hoyt, Grant;Yang, Phillip;Rosenberg, Jarrett;Robbins, Robert C.;Wu, Joseph C.
通讯作者：
Wu, Joseph C.
影响因子：
9.3
作者：
Munshi R;Hsu C;Himmelfarb J
通讯作者：
Himmelfarb J
影响因子：
37.8
作者：
Li, Zongjin;Wu, Jenny C.;Wu, Joseph C.
通讯作者：
Wu, Joseph C.
DOI：
10.1152/ajpheart.00196.2002
发表时间：
2002-11-01
影响因子：
4.8
作者：
Brodsky, SV;Gao, SJ;Goligorsky, MS
通讯作者：
Goligorsky, MS
DOI：
10.1152/ajprenal.00019.2010
发表时间：
2010-08
期刊：
American journal of physiology. Renal physiology
影响因子：
--
作者：
Odongua Sangidorj;S. Yang;H. Jang;J. P. Lee;R. Cha;S. M. Kim;C. Lim;Y. S. Kim
通讯作者：
Odongua Sangidorj;S. Yang;H. Jang;J. P. Lee;R. Cha;S. M. Kim;C. Lim;Y. S. Kim