Department of Molecular Medicine, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
J Am Soc Nephrol. 2012 Nov;23(11):1857-68. doi: 10.1681/ASN.2012050505. Epub 2012 Oct 18.
The shortage of transplantable organs provides an impetus to develop tissue-engineered alternatives. Producing tissues similar to immature kidneys from simple suspensions of fully dissociated embryonic renal cells is possible in vitro, but glomeruli do not form in the avascular environment. Here, we constructed renal organoids from single-cell suspensions derived from E11.5 kidneys and then implanted these organoids below the kidney capsule of a living rat host. This implantation resulted in further maturation of kidney tissue, formation of vascularized glomeruli with fully differentiated capillary walls, including the slit diaphragm, and appearance of erythropoietin-producing cells. The implanted tissue exhibited physiologic functions, including tubular reabsorption of macromolecules, that gained access to the tubular lumen on glomerular filtration. The ability to generate vascularized nephrons from single-cell suspensions marks a significant step to the long-term goal of replacing renal function by a tissue-engineered kidney.
移植器官的短缺为开发组织工程替代物提供了动力。从完全解离的胚胎肾细胞的简单悬浮液中体外产生类似于未成熟肾脏的组织是可能的,但在无血管环境中不会形成肾小球。在这里,我们从 E11.5 肾脏的单细胞悬浮液中构建了肾类器官,然后将这些类器官植入活体大鼠宿主的肾包膜下。这种植入导致肾脏组织进一步成熟,形成血管化的肾小球,具有完全分化的毛细血管壁,包括裂孔隔膜,并出现产生促红细胞生成素的细胞。植入的组织表现出生理功能,包括对大分子的管状重吸收,这些大分子通过肾小球滤过进入管状腔。从单细胞悬浮液中生成血管化肾单位的能力标志着朝着通过组织工程肾脏替代肾功能的长期目标迈出了重要一步。