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胚胎肾多能祖细胞在急性肾衰竭中的再生潜力

Regenerative potential of embryonic renal multipotent progenitors in acute renal failure.

作者信息

Lazzeri Elena, Crescioli Clara, Ronconi Elisa, Mazzinghi Benedetta, Sagrinati Costanza, Netti Giuseppe Stefano, Angelotti Maria Lucia, Parente Eliana, Ballerini Lara, Cosmi Lorenzo, Maggi Laura, Gesualdo Loreto, Rotondi Mario, Annunziato Francesco, Maggi Enrico, Lasagni Laura, Serio Mario, Romagnani Sergio, Vannelli Gabriella Barbara, Romagnani Paola

机构信息

Excellence Center for Research, Transfer and High Education for the Development of DE NOVO THERAPIES, University of Florence, Florence, Italy.

出版信息

J Am Soc Nephrol. 2007 Dec;18(12):3128-38. doi: 10.1681/ASN.2007020210. Epub 2007 Oct 31.

Abstract

Bone marrow-and adult kidney-derived stem/progenitor cells hold promise in the development of therapies for renal failure. Here is reported the identification and characterization of renal multipotent progenitors in human embryonic kidneys that share CD24 and CD133 surface expression with adult renal progenitors and have the capacity for self-renewal and multilineage differentiation. It was found that these CD24+CD133+ cells constitute the early primordial nephron but progressively disappear during nephron development until they become selectively localized to the urinary pole of Bowman's capsule. When isolated and injected into SCID mice with acute renal failure from glycerol-induced rhabdomyolysis, these cells regenerated different portions of the nephron, reduced tissue necrosis and fibrosis, and significantly improved renal function. No tumorigenic potential was observed. It is concluded that CD24+CD133+ cells represent a subset of multipotent embryonic progenitors that persist in human kidneys from early stages of nephrogenesis. The ability of these cells to repair renal damage, together with their apparent lack of tumorigenicity, suggests their potential in the treatment of renal failure.

摘要

骨髓和成年肾脏来源的干细胞/祖细胞在肾衰竭治疗方法的开发中具有前景。本文报道了在人类胚胎肾脏中鉴定和表征肾多能祖细胞,这些祖细胞与成年肾祖细胞共享CD24和CD133表面表达,并且具有自我更新和多谱系分化的能力。研究发现,这些CD24+CD133+细胞构成早期原始肾单位,但在肾单位发育过程中逐渐消失,直到它们选择性地定位于鲍曼囊的尿极。当将这些细胞分离并注射到由甘油诱导的横纹肌溶解引起急性肾衰竭的SCID小鼠中时,这些细胞使肾单位的不同部分再生,减少了组织坏死和纤维化,并显著改善了肾功能。未观察到致瘤潜力。结论是,CD24+CD133+细胞代表多能胚胎祖细胞的一个亚群,它们从肾发生的早期阶段就存在于人类肾脏中。这些细胞修复肾损伤的能力,以及它们明显缺乏致瘤性,表明它们在肾衰竭治疗中的潜力。

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