Stem cells: a potential treatment option for kidney diseases

Abstract

The prevalence of kidney diseases is emerging as a public health problem. Stem cells (SCs), currently considered as a promising tool for therapeutic application, have aroused considerable interest and expectations. With self-renewal capabilities and great potential for proliferation and differentiation, stem cell therapy opens new avenues for the development of renal function and structural repair in kidney diseases. Mounting evidence suggests that stem cells exert a therapeutic effect mainly by replacing damaged tissues and paracrine pathways. The benefits of various types of SCs in acute kidney disease and chronic kidney disease have been demonstrated in preclinical studies, and preliminary results of clinical trials present its safety and tolerability. This review will focus on the stem cell-based therapy approaches for the treatment of kidney diseases, including various cell sources used, possible mechanisms involved, and outcomes that are generated so far, along with prospects and challenges in clinical application.

Stem/progenitor cell in kidney: characteristics, homing, coordination, and maintenance

“…The stromal-derived factor-1 (SDF-1)/chemokine (C-X-C motif) receptor 4 (CXCR4) axis plays an important role in the migration of BMDCs and renal stem/progenitor cells [ 116 , 117 ]. SDF-1, a main regulator of migration and mobilization for BMDCs [ 118 ], is upregulated in the surrounding resident cells of necrotic area [ 14 , 119 , 120 ]. CXCR4 and CXCR7, the receptors of SDF-1, are highly expressed in renal stem/progenitor cells [ 119 , 121 ].…”

“…EVs include exosomes, microparticles, or microvesicles [ 146 – 149 ]. Notably, kidney stem/progenitor cells could secrete IL-15, endothelial growth factor, HGF, leukemia inhibitory factor, inhibin-A, decorin, VEGF, and recombinant human bone morphogenetic protein (BMP)-7 through direct release or through shuttling mRNA or miRNA using EVs, to repair renal injury, alleviate inflammation, and retard fibrosis [ 14 , 150 – 152 ]. A study shows that the effects of EVs of kidney stem/progenitor cells may primarily depend on the shuttling of mRNA or miRNA, because after treatment with RNase, EVs are not effective on improving kidney function and aiding recovery.…”

“…The mesenchymal stem cell (MSC) population plays the important role in the embryogenesis of kidney [ 12 , 13 ]. While in the adult kidney, the two different sources for stem/progenitor cells including resident renal stem/progenitor cells and circulating stem/progenitor cells which are mainly derived from bone marrow, also greatly facilitate the local repair processes through anti-inflammation and immune-modulatory effects [ 14 – 17 ]. There have been some studies showing that stem/progenitor cells could ameliorate kidney injury and improve renal function in ischemia/reperfusion injury (IRI) [ 3 , 5 , 15 , 18 , 19 ], nephrotic syndrome [ 20 ], acute renal failure by intramuscular injection of glycerol [ 21 – 23 ], and an adriamycin-induced model [ 24 ].…”

Roles of Krüppel‐like factor 5 in kidney disease

“…However, dialysis is not an ideal treatment option due to adverse effects of dialysis on patients’ quality of life and the exorbitant medical costs associated with it. The shortage of donor kidneys and incidence of organ rejection has also limited the use of kidney transplantation 102 . Therefore, identifying new therapies that will slow down progression to ESRD or will prevent kidney disease in a way that prolongs patients’ lives and improves their quality of life is necessary.…”

“…PSCs have unlimited self‐renewal capacity and the ability to differentiate into various types of cells including kidney lineage cells. Kidney organoids paved the way for kidney disease modelling, drug discovery and possibly for transplantation in the future 102 . Induced pluripotent stem (iPS) cells, first reported by Takahashi et al, are a type of PSCs, reprogrammed from somatic cells by four‐transcription factors, including KLF4, OCT4, SOX2 and c‐Myc 103 .…”