Isolation and characterization of kidney-derived stem cells

Isolation and characterization of kidney-derived stem cells
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DOI:
10.1681/asn.2006030275
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发表时间:
2006-11-01
影响因子:
13.6
通讯作者:
Rosenberg, Mark E.
Rosenberg, Mark E.
中科院分区:
医学1区
文献类型:
--
作者:
Gupta, Sandeep;Verfaillie, Catherine;Rosenberg, Mark E.

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急性肾损伤之后是受损肾小管上皮细胞的再生。本研究的目的是验证肾干细胞存在于成人肾脏中并参与修复过程的假设。从大鼠肾脏中分离出一种独特的细胞群,其行为方式与肾干细胞一致,称为多能肾祖细胞(MRPC)。这些细胞的特征包括纺锤形形态;自我更新> 200个群体,没有衰老的证据;正常的核型和DNA分析;表达波形蛋白、CD 90(thyl.1)、Pax-2和Oct 4,但不表达细胞角蛋白、MHC I类或II类或更分化细胞的其他标志物。通过逆转录酶-PCR和免疫组织化学检测,MRPC细胞被诱导表达内皮、肝细胞和神经标志物的能力证明了其可塑性。当注射到未损伤肾的包膜下或肾缺血-再灌注损伤后动脉内时,细胞可以分化成肾小管。Oct 4在成人肾脏的一些肾小管细胞中表达,表明这些细胞可能是候选的肾脏干细胞。提示MRPC参与了肾脏对急性损伤的再生反应。
Acute kidney injury is followed by regeneration of damaged renal tubular epithelial cells. The purpose of this study was to test the hypothesis that renal stem cells exist in the adult kidney and participate in the repair process. A unique population of cells that behave in a manner that is consistent with a renal stem cell were isolated from rat kidneys and were termed multipotent renal progenitor cells (MRPC). Features of these cells include spindle-shaped morphology; self-renewal for > 200 population doublings without evidence for senescence; normal karyotype and DNA analysis; and expression of vimentin, CD90 (thyl.1), Pax-2, and Oct4 but not cytokeratin, MHC class I or II, or other markers of more differentiated cells. MRPC exhibit plasticity that is demonstrated by the ability of the cells to be induced to express endothelial, hepatocyte, and neural markers by reverse transcriptase-PCR and immunohistochemistry. The cells can differentiate into renal tubules when injected under the capsule of an uninjured kidney or intra-arterially after renal ischemia-reperfusion injury. Oct4 expression was seen in some tubular cells in the adult kidney, suggesting these cells may be candidate renal stem cells. It is proposed that MRPC participate in the regenerative response of the kidney to acute injury.