Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells
Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells
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DOI：
10.1172/jci22593
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发表时间：
2005-07-01
影响因子：
15.9
通讯作者：
Bonventre, JV
中科院分区：
文献类型：
--
作者：
Duffield, JS;Park, KM;Bonventre, JV
缺血导致肾小管细胞损伤和肾功能异常。肾脏能够恢复肾小管的形态和功能。最近，有人提出，细胞再生缺血损伤的小管来源于骨髓干细胞。我们研究了表达GFP或细菌P-gal或仅在骨髓来源的细胞中携带雄性Y染色体的嵌合小鼠的肾脏修复。在GFP嵌合体中，缺血损伤后一些间质细胞而不是肾小管细胞表达GFP。超过99%的GFP间质细胞是白细胞。在具有雄性骨髓的雌性小鼠中，偶见肾小管细胞（0.06%）显示Y染色体阳性，但去卷积显微镜显示这些是人为的。在β-gal嵌合体中，一些肾小管细胞也似乎表达β-gal，如通过X-gal染色所评估的，但是在内源性（哺乳动物）β-gal抑制后，在缺血性损伤后没有发现肾小管细胞用X-gal染色。虽然没有骨髓源性肾小管细胞，但许多肾小管细胞表达增殖细胞核抗原，这反映了内源性存活肾小管细胞的高增殖率。静脉注射骨髓间充质干细胞后。细胞，缺血后功能性肾损害减少，但没有证据表明这些细胞分化为肾小管细胞。因此，我们的数据表明骨髓源性细胞对缺血性损伤后上皮完整性的恢复没有显着贡献。这可能是内在的肾小管细胞增殖解释缺血后肾小管上皮细胞功能上的显著补充。
Ischemia causes kidney tubular cell damage and abnormal renal function. The kidney is capable of morphological restoration of tubules and recovery of function. Recently, it has been suggested that cells repopulating the ischemically injured tubule derive from bone marrow stem cells. We studied kidney repair in chimeric mice expressing GFP or bacterial P-gal or harboring the male Y chromosome exclusively in bone marrow-derived cells. In GFP chimeras, some interstitial cells but not tubular cells expressed GFP after ischemic injury. More than 99% of those GFP interstitial cells were leukocytes. In female mice with male bone marrow, occasional tubular cells (0.06%) appeared to be positive for the Y chromosome, but deconvolution microscopy revealed these to be artifactual. In beta-gal chimeras, some tubular cells also appeared to express beta-gal as assessed by X-gal staining, but following suppression of endogenous (mammalian) beta-gal, no tubular cells could be found that stained with X-gal after ischemic injury. Whereas there was an absence of bone marrow-derived tubular cells, many tubular cells expressed proliferating cell nuclear antigen, which is reflective of a high proliferative rate of endogenous surviving tubular cells. Upon i.v. injection of bone marrow mesenchymal stromal. cells, postischemic functional renal impairment was reduced, but there was no evidence of differentiation of these cells into tubular cells of the kidney. Thus, our data indicate that bone marrow-derived cells do not make a significant contribution to the restoration of epithelial integrity after an ischemic insult. It is likely that intrinsic tubular cell proliferation accounts for functionally significant replenishment of the tubular epithelium after ischemia.