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通过胎儿肾细胞移植进行肾组织重建:胎儿肾细胞妊娠阶段的影响。

Kidney tissue reconstruction by fetal kidney cell transplantation: effect of gestation stage of fetal kidney cells.

作者信息

Kim Sang-Soo, Gwak So-Jung, Han Joungho, Park Heung Jae, Park Moon Hyang, Song Kang Won, Cho Seung Woo, Rhee Yun Hee, Chung Hyung Min, Kim Byung-Soo

机构信息

Department of Bioengineering, Hanyang University, 17 Haengdang-dong, Seongdong-ku, Seoul 133-791, Korea.

出版信息

Stem Cells. 2007 Jun;25(6):1393-401. doi: 10.1634/stemcells.2006-0183.

Abstract

Dialysis and kidney transplantation, current therapies for kidney failure, have limitations such as severe complications, donor shortage, and immune-related problems. The development of an alternative treatment for kidney failure is demanded. The present study shows that the transplantation of fetal kidney cells reconstitutes functional kidney tissue, and that the gestation stage of kidney cells influences the kidney reconstitution. Fetal kidney cells were isolated from metanephroi of rat fetuses at various gestation stages and transplanted into the omentum or kidney of immunodeficient mice. Immunophenotype analysis of fetal kidney cells showed apparent expression of stem cell markers. Three weeks after transplantation, histological analyses of retrieved grafts revealed the formation of kidney structures, including fluorescently labeled transplanted cells, suggesting the potential of fetal kidney cells to reconstitute kidney tissues. The grafts retrieved from omentum contained cystic fluids with concentrated solutes. However, transplanted early fetal kidney cells had also differentiated into nonrenal tissues such as bone and cartilage. In addition, transplantation of fetal kidney cells from a later gestation stage resulted in poor kidney structure formation. Kidney-specific genes were strongly expressed in the earlier cell transplants. The cells at an earlier gestation stage had higher colony forming ability than the cells at a later stage. This study demonstrates the reconstitution of kidney tissue by transplanting fetal kidney cells and the presence of an optimal time window in which fetal kidney cells regenerate kidney tissues. Disclosure of potential conflicts of interest is found at the end of this article.

摘要

透析和肾脏移植作为目前治疗肾衰竭的方法,存在诸如严重并发症、供体短缺和免疫相关问题等局限性。因此需要开发一种治疗肾衰竭的替代方法。本研究表明,移植胎儿肾细胞可重建功能性肾组织,并且肾细胞的妊娠阶段会影响肾脏重建。从不同妊娠阶段的大鼠胎儿后肾中分离出胎儿肾细胞,并将其移植到免疫缺陷小鼠的大网膜或肾脏中。对胎儿肾细胞的免疫表型分析显示干细胞标志物有明显表达。移植三周后,对回收移植物的组织学分析显示形成了肾脏结构,包括荧光标记的移植细胞,这表明胎儿肾细胞具有重建肾组织的潜力。从大网膜回收的移植物含有溶质浓缩的囊液。然而,移植的早期胎儿肾细胞也分化成了非肾组织,如骨骼和软骨。此外,移植妊娠后期的胎儿肾细胞导致肾脏结构形成不佳。肾脏特异性基因在早期细胞移植中强烈表达。妊娠早期的细胞比后期的细胞具有更高的集落形成能力。本研究证明了通过移植胎儿肾细胞可重建肾组织,并且存在胎儿肾细胞再生肾组织的最佳时间窗。潜在利益冲突的披露见本文末尾。

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