Tajima Kazuki, Yagi Hiroshi, Morisaku Toshinori, Nishi Kotaro, Kushige Hiroko, Kojima Hideaki, Higashi Hisanobu, Kuroda Kohei, Kitago Minoru, Adachi Shungo, Natsume Tohru, Nishimura Kumiko, Oya Mototsugu, Kitagawa Yuko
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku, Tokyo, Japan.
Department of Small Animal Internal Medicine, Kitasato University School of Veterinary Medicine, Higashi 23-35-1, Towada, Aomori, Japan.
NPJ Regen Med. 2022 Feb 28;7(1):18. doi: 10.1038/s41536-022-00213-y.
It has not been considered that nephrons regenerate in adult mammals. We present that an organ-derived extracellular matrix in situ induces nephron regeneration in a preclinical model. A porcine kidney-derived extracellular matrix was sutured onto the surface of partial nephrectomy (PN)-treated kidney. Twenty-eight days after implantation, glomeruli, vessels, and renal tubules, characteristic of nephrons, were histologically observed within the matrix. No fibrillogenesis was observed in the matrix nor the matrix-sutured kidney, although this occurred in a PN kidney without the matrix, indicating the structures were newly induced by the matrix. The expression of renal progenitor markers, including Sall1, Six2, and WT-1, within the matrix supported the induction of nephron regeneration by the matrix. Furthermore, active blood flow was observed inside the matrix using computed tomography. The matrix provides structural and functional foundations for the development of cell-free scaffolds with a remarkably low risk of immune rejection and cancerization.
成年哺乳动物的肾单位能够再生这一观点此前未被考虑过。我们提出，一种器官来源的细胞外基质在原位可诱导临床前模型中的肾单位再生。将猪肾来源的细胞外基质缝合到接受部分肾切除术（PN）治疗的肾脏表面。植入28天后，在基质内组织学观察到了具有肾单位特征的肾小球、血管和肾小管。在基质及缝合了基质的肾脏中均未观察到纤维形成，而在未植入基质的PN肾脏中则出现了纤维形成，这表明这些结构是由基质新诱导生成的。基质内肾祖细胞标志物（包括Sall1、Six2和WT-1）的表达支持了基质对肾单位再生的诱导作用。此外，使用计算机断层扫描观察到基质内部有活跃的血流。该基质为开发具有极低免疫排斥和癌变风险的无细胞支架提供了结构和功能基础。
