Abstract
The prevalence of renal diseases is emerging as a public health problem. Despite major progress in supportive therapy, mortality rates among patients remain high. In an attempt to find innovative treatments to stimulate kidney regeneration, stem cell-based technology has been proposed as a potentially promising strategy. Here, we summarise the renoprotective potential of pluripotent and adult stem cell therapy in experimental models of acute and chronic kidney injury and we explore the different mechanisms at the basis of stem cell-induced kidney regeneration. Specifically, cell engraftment, incorporation into renal structures, or paracrine activities of embryonic or induced pluripotent stem cells as well as mesenchymal stem cells and renal precursors are analysed. We also discuss the relevance of stem cell secretome-derived bioproducts, including soluble factors and extracellular vesicles, and the option of using them as cell-free therapy to induce reparative processes. The translation of the experimental results into clinical trials is also addressed, highlighting the safety and feasibility of stem cell treatments in patients with kidney injury.
Highlights
The increasing incidence of kidney diseases raises considerable concerns regarding human health worldwide
This review describes a wide range of pre-clinical reports on stem cell-based therapy in experimental acute kidney injury (AKI) and chronic kidney diseases (CKD), summarizing current knowledge and discussing criticisms for moving to the clinic
Another study described the efficacy of OSR1+SIX2+ renal progenitors derived from induced pluripotent stem cells (iPSCs) and transplanted under the kidney capsule to improve renal function in terms of reducing blood urea nitrogen (BUN) and attenuating histopathological changes in an AKI model induced by ischaemia and reperfusion (I/R) [102,103]
Summary
The increasing incidence of kidney diseases raises considerable concerns regarding human health worldwide. The decades that followed were characterised by the first long-term successful human kidney transplantation from a living donor carried out by Dr Joseph Murray, who received the Nobel Prize in Medicine for this achievement [3,4] This was a huge step forward but highlighted the need to better understand the immune system to prevent rejection [5]. The new goal of delaying the progression of kidney disease was achieved through the discovery of drugs that inhibit the renin angiotensin aldosterone system (RAAS) [8] It is not currently clear what the necessary step is, but it seems to be in the direction of regenerative medicine.
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