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首页> 外文期刊>Stem Cells >Bone marrow-derived cells contribute to podocyte regeneration and amelioration of renal disease in a mouse model of Alport syndrome.
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Bone marrow-derived cells contribute to podocyte regeneration and amelioration of renal disease in a mouse model of Alport syndrome.

机译：在Alport综合征的小鼠模型中，骨髓来源的细胞有助于足细胞的再生和肾脏疾病的改善。

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摘要

In a model of autosomally recessive Alport syndrome, mice that lack the alpha3 chain of collagen IV (Col4alpha3(-/-)) develop progressive glomerular damage leading to renal failure. The proposed mechanism is that podocytes fail to synthesize normal glomerular basement membrane, so the collagen IV network is unstable and easily degraded. We used this model to study whether bone marrow (BM) transplantation can rectify this podocyte defect by correcting the deficiency in Col4alpha3. Female C57BL/6 Col4alpha3(-/-) (-/-) mice were transplanted with whole BM from male wild-type (+/+) mice. Control female -/- mice received BM from male -/- littermates. Serum urea and creatinine levels were significantly lower in recipients of +/+ BM compared with those of -/- BM 20 weeks post-transplant. Glomerular scarring and interstitial fibrosis were also significantly decreased. Donor-derived cells were detected by in situ hybridization (ISH) for the Y chromosome, and fluorescence and confocal microscopy indicated that some showed an apparent podocyte phenotype in mice transplanted with +/+ BM. Glomeruli of these mice showed small foci of staining for alpha3(IV) protein by immunofluorescence. alpha3(IV) mRNA was detectable by reverse transcription-polymerase chain reaction and ISH in some mice transplanted with +/+ BM but not -/- BM. However, a single injection of mesenchymal stem cells from +/+ mice to irradiated -/- recipients did not improve renal disease. Our data show that improved renal function in Col4alpha3(-/-) mice results from BM transplantation from wild-type donors, and the mechanism by which this occurs may in part involve generation of podocytes without the gene defect.
机译：在常染色体隐性遗传性Alport综合征模型中，缺少胶原IV（胶原）的α3链的小鼠（Col4alpha3（-/-））发展为肾小球进行性肾小球损害，从而导致肾功能衰竭。提出的机制是足细胞不能合成正常的肾小球基底膜，因此胶原IV网络不稳定且易于降解。我们使用该模型来研究骨髓（BM）移植是否可以通过纠正Col4alpha3的缺陷来纠正这种足细胞缺陷。将雌性C57BL / 6 Col4alpha3（-/-）（-/-）小鼠移植了来自雄性野生型（+ / +）小鼠的完整BM。对照雌性-/-小鼠从雄性-/-同窝仔接受BM。移植后20周，+ / + BM的接受者的血清尿素和肌酐水平显着低于-/-BM的接受者。肾小球瘢痕形成和间质纤维化也明显减少。通过原位杂交（ISH）检测Y染色体的供体来源的细胞，荧光和共聚焦显微镜检查表明，一些小鼠在+ / + BM移植的小鼠中表现出明显的足细胞表型。这些小鼠的肾小球通过免疫荧光显示出小的α3（IV）蛋白染色灶。通过逆转录-聚合酶链反应和ISH在一些+ / + BM而非-/-BM移植的小鼠中可检测到alpha3（IV）mRNA。但是，从+ / +小鼠向辐照的-/-受体单次注射间充质干细胞并不能改善肾脏疾病。我们的数据表明，Col4alpha3（-/-）小鼠肾功能的改善是由野生型供体的BM移植导致的，其发生的机制可能部分涉及没有基因缺陷的足细胞的生成。

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