Chen Dong, Chen Zhiyong, Zhang Yuning, Park Chanyoung, Al-Omari Ahmed, Moeckel Gilbert W
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut; and.
Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
Am J Physiol Renal Physiol. 2014 Jul 1;307(1):F64-74. doi: 10.1152/ajprenal.00547.2013. Epub 2014 May 7.
This study is aimed at characterizing medullary interstitial progenitor cells and to examine their capacity to induce tubular epithelial cell migration and proliferation. We have isolated a progenitor cell side population from a primary medullary interstitial cell line. We show that the medullary progenitor cells (MPCs) express CD24, CD44, CXCR7, CXCR4, nestin, and PAX7. MPCs are CD34 negative, which indicates that they are not bone marrow-derived stem cells. MPCs survive >50 passages, and when grown in epithelial differentiation medium develop phenotypic characteristics of epithelial cells. Inner medulla collecting duct (IMCD3) cells treated with conditioned medium from MPCs show significantly accelerated cell proliferation and migration. Conditioned medium from PGE2-treated MPCs induce tubule formation in IMCD3 cells grown in 3D Matrigel. Moreover, most of the MPCs express the pericyte marker PDGFR-b. Our study shows that the medullary interstitium harbors a side population of progenitor cells that can differentiate to epithelial cells and can stimulate tubular epithelial cell migration and proliferation. The findings of this study suggest that medullary pericyte/progenitor cells may play a critical role in collecting duct cell injury repair.
本研究旨在对髓质间质祖细胞进行特性描述,并检测其诱导肾小管上皮细胞迁移和增殖的能力。我们从原代髓质间质细胞系中分离出了祖细胞侧群。我们发现,髓质祖细胞(MPCs)表达CD24、CD44、CXCR7、CXCR4、巢蛋白和PAX7。MPCs为CD34阴性,这表明它们不是骨髓来源的干细胞。MPCs可传代超过50次,在上皮分化培养基中培养时会呈现上皮细胞的表型特征。用MPCs的条件培养基处理的内髓集合管(IMCD3)细胞显示出细胞增殖和迁移显著加速。经前列腺素E2处理的MPCs的条件培养基可诱导在三维基质胶中培养的IMCD3细胞形成小管。此外,大多数MPCs表达周细胞标志物血小板衍生生长因子受体β(PDGFR-b)。我们的研究表明,髓质间质中存在一群祖细胞,它们可分化为上皮细胞,并能刺激肾小管上皮细胞迁移和增殖。本研究结果提示,髓质周细胞/祖细胞可能在集合管细胞损伤修复中起关键作用。