The Skate Weighs in on Kidney Regeneration

[摘要] Research into kidney organogenesis has seen dramatic growth in recent years, fueled not only by new data on epithelial cell differentiation and the function of genes expressed in the kidney but also by a renewed interest in stem cell biology and its potential application to treating disease. Since the pioneering work of Grobstein in the middle 1950s (1), it has been known that the formation of new nephrons in the developing mammalian kidney is dependent on an interaction between a mass of fibroblastic cells, the metanephric mesenchyme or renal progenitor cells, and the branching epithelium derived from the ureteric bud, the future collecting system. In the intervening years, the search for the identity of signals mediating the conversion of mesenchymal progenitor cells to epithelium and nephron formation has taken many forms; from mouse gene knockout experiments to biochemical analyses of factors secreted by embryonic kidney cells and cell lines (2). Underlying this search are these questions: What cellular processes are required for continued growth and differentiation of kidney tissue? How are these processes regulated at the molecular level to generate the elaborate architecture of the mature kidney and the functional integration of its varied cell types? How are growth and proliferation of renal progenitor cells coordinated with nephron differentiation to result in uniformly sized kidneys? In addition to illuminating the origins of the kidney, the answers to these questions could have broad implications for treatment of kidney injury and end-stage renal disease. Unlike the liver, the kidney has a limited regenerative capacity. Kidney resection in mammals causes compensatory contralateral hypertrophy but no new nephron formation. The response to tubular damage in the mammalian kidney is an important aspect of injury repair but is largely limited to local reproliferation of epithelial cells to cover the denuded basement membrane (3). Damage to glomeruli seen in glomerulosclerosis is for the most part irreversible and leads finally to nephron degeneration (4). Translating basic discoveries in nephrogenesis to therapies that might enhance kidney regeneration after injury remains an attractive goal. In a parallel vein, recent discoveries detailing the unexpected plasticity of tissue and bone marrow stem cells is generating optimism that some aspects of development may be recapitulated in the context of the adult organ and allow new avenues for tissue repair.

[学科分类] 泌尿医学

[关键词] Bone marrow necrosis;Sickle cell disease;Hyperhemolysis syndrome