Peer-review started: August 11, 2015
First decision: September 21, 2015
Revised: September 27, 2015
Accepted: November 23, 2015
Article in press: November 25, 2015
Published online: January 6, 2016
Processing time: 150 Days and 7.1 Hours
Kidney regeneration is a challenging but promising strategy aimed at reducing the progression to end-stage renal disease (ESRD) and improving the quality of life of patients with ESRD. Adult stem cells are multipotent stem cells that reside in various tissues, such as bone marrow and adipose tissue. Although intensive studies to isolate kidney stem/progenitor cells from the adult kidney have been performed, it remains controversial whether stem/progenitor cells actually exist in the mammalian adult kidney. The efficacy of mesenchymal stem cells (MSCs) in the recovery of kidney function has been demonstrated in animal nephropathy models, such as acute tubular injury, glomerulonephritis, renal artery stenosis, and remnant kidney. However, their beneficial effects seem to be mediated largely via their paracrine effects rather than their direct differentiation into renal parenchymal cells. MSCs not only secrete bioactive molecules directly into the circulation, but they also release various molecules, such as proteins, mRNA, and microRNA, in membrane-covered vesicles. A detailed analysis of these molecules and an exploration of the optimal combination of these molecules will enable the treatment of patients with kidney disease without using stem cells. Another option for the treatment of patients with kidney disease using adult somatic cells is a direct/indirect reprogramming of adult somatic cells into kidney stem/progenitor cells. Although many hurdles still need to be overcome, this strategy will enable bona fide kidney regeneration rather than kidney repair using remnant renal parenchymal cells.
Core tip: Although intensive studies have been performed to isolate kidney stem/progenitor cells from the mammalian adult kidney, whether stem/progenitor cells actually exist in the adult kidney is still debated. Mesenchymal stem cells seem to exert beneficial effects via paracrine effects rather than by direct differentiation into renal parenchymal cells. In this review, we also introduce potential roles of extracellular vesicles released from stem cells and direct/indirect reprogramming of adult somatic cells by which kidney stem/progenitor cells will be formed in the future.