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The Lymph Node as a New Site for Kidney Organogenesis

机译:淋巴结作为肾脏器官发生的新场所

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The shortage of organs for kidney transplantation has created the need to develop new strategies to restore renal structure and function. Given our recent finding that the lymph node (LN) can serve as an in vivo factory to generate or sustain complex structures like liver, pancreas, and thymus, we investigated whether it could also support kidney organogenesis from mouse renal embryonic tissue (metanephroi). Here we provide the first evidence that metanephroi acquired a mature phenotype upon injection into LN, and host cells likely contributed to this process. Urine-like fluid-containing cysts were observed in several grafts 12 weeks post-transplantation, indicating metanephroi transplants' ability to excrete products filtered from the blood. Importantly, the kidney graft adapted to a loss of host renal mass, speeding its development. Thus, the LN might provide a unique tool for studying the mechanisms of renal maturation, cell proliferation, and fluid secretion during cyst development. Moreover, we provide evidence that inside the LN, short-term cultured embryonic kidney cells stimulated with the Wnt agonist R-Spondin 2 gave rise to a monomorphic neuron-like cell population expressing the neuronal 200-kDa neurofilament heavy marker. This finding indicates that the LN might be used to validate the differentiation potential of candidate stem cells in regenerative nephrology.
机译:肾脏移植器官的短缺导致需要开发新的策略来恢复肾脏结构和功能。鉴于我们最近的发现,淋巴结(LN)可以作为体内工厂来产生或维持肝脏,胰腺和胸腺等复杂结构,因此我们研究了它是否还可以支持小鼠肾脏胚胎组织(metanephroi)的肾脏器官发生。在这里,我们提供了第一个证据,即肾上腺素注射到LN中后获得了成熟的表型,宿主细胞可能对这一过程有所贡献。移植后12周,在数个移植物中观察到了含有尿样液的囊肿,这表明前肾移植可以排泄从血液中滤出的产物。重要的是,肾移植物适应了宿主肾重量的损失,加速了其发展。因此,LN可能为研究肾脏在囊肿形成过程中成熟,细胞增殖和液体分泌的机制提供独特的工具。此外,我们提供的证据表明,在LN内,用Wnt激动剂R-Spondin 2刺激的短期培养的胚胎肾细胞产生了表达神经元200 kDa神经丝重标记的单态神经元样细胞群。这一发现表明,LN可用于验证再生肾病学中候选干细胞的分化潜能。

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