Pulsed electromagnetic fields (PEMF) are employed as a non-invasive medicinal therapy, especially in the orthopedic field to stimulate bone regeneration. However, the effect of PEMF on skeletal muscle cells (SkMC) has been understudied. Here, we studied the potentiality of 1.5 mT PEMF to stimulate early regeneration of human SkMC. We showed that human SkMC stimulated with 1.5 mT PEMF for four hours repeated for two days can stimulate cell proliferation without inducing cell apoptosis or significant impairment of the metabolic activity. Interestingly, when we simulated physical damage of the muscle tissue by a scratch, we found that the same PEMF treatment can speed up the regenerative process, inducing a more complete cell migration to close the scratch and wound healing. Moreover, we investigated the molecular pattern induced by PEMF among 26 stress-related cell proteins. We found that the expression of 10 proteins increased after two consecutive days of PEMF stimulation for 4 h, and most of them were involved in response processes to oxidative stress. Among these proteins, we found that heat shock protein 70 (HSP70), which can promote muscle recovery, inhibits apoptosis and decreases inflammation in skeletal muscle, together with thioredoxin, paraoxonase, and superoxide dismutase (SOD2), which can also promote skeletal muscle regeneration following injury. Altogether, these data support the possibility of using PEMF to increase SkMC regeneration and, for the first time, suggest a possible molecular mechanism, which consists of sustaining the expression of antioxidant enzymes to control the important inflammatory and oxidative process occurring following muscle damage.

Long non-coding RNAs (lncRNAs) are a large, heterogeneous class of transcripts and key regulators of gene expression at both the transcriptional and post-transcriptional levels in different cellular contexts and biological processes. Understanding the potential mechanisms of action of lncRNAs and their role in disease onset and development may open up new possibilities for therapeutic approaches in the future. LncRNAs also play an important role in renal pathogenesis. However, little is known about lncRNAs that are expressed in the healthy kidney and that are involved in renal cell homeostasis and development, and even less is known about lncRNAs involved in human adult renal stem/progenitor cells (ARPC) homeostasis. Here we give a thorough overview of the biogenesis, degradation, and functions of lncRNAs and highlight our current understanding of their functional roles in kidney diseases. We also discuss how lncRNAs regulate stem cell biology, focusing finally on their role in human adult renal stem/progenitor cells, in which the lncRNA HOTAIR prevents them from becoming senescent and supports these cells to secrete high quantities of α-Klotho, an anti-aging protein capable of influencing the surrounding tissues and therefore modulating the renal aging.

Stem and progenitor cells have been observed to contribute to regenerative processes in acute renal failure and chronic kidney disease. Recent research has delved into the intricate mechanisms by which stem and progenitor cells exert their influence on kidney diseases. Understanding how these cells integrate with the existing renal architecture and their response to injury could pave the way for innovative treatment strategies aimed at promoting kidney repair and regeneration. Overall, the role of stem and progenitor cells in kidney diseases is multifaceted, with their ability to contribute to tissue regeneration, immune modulation, and the maintenance of renal homeostasis. Here, we review the studies that we have available today about the involvement of stem and progenitor cells both in regenerative therapies and in the causes of renal diseases, as well as in natural healing mechanisms, taking into account the main kidney disorders, such as IgA nephropathy, lupus nephritis, diabetic nephropathy, C3 glomerulopathy, focal segmental glomerulosclerosis, idiopathic membranous nephropathy, anti-glomerular basement membrane glomerulonephritis, and ANCA-associated crescentic glomerulonephritis. Moreover, based on the comprehensive data available in the framework of the specific kidney diseases on stem cells and renal progenitors, we hypothesize a possible role of adult renal progenitors in exacerbating or recovering the illness.

The rapidly developing field of renal spheroids and organoids has emerged as a valuable tool for modeling nephrotoxicity, kidney disorders, and kidney development. However, existing studies have relied on intricate and sophisticated differentiation protocols to generate organoids and tubuloids, necessitating the external administration of multiple growth factors within precise timeframes. In our study, we demonstrated that human adult renal progenitor cells (ARPCs) isolated from urine of both healthy subjects or patients, have the capacity to form spheroids that naturally can form very long tubule-like structures. Importantly, the generation of these tubule-like formations is driven solely by ARPCs, without the need for the external use of chemokines or growth factors to artificially induce the process. These tubule-like structures exhibit expression of structural and functional renal tubule markers and bear, in some cases, striking structural similarities to various nephron regions, including the distal convoluted tubule, the loop of Henle, and proximal convoluted tubules. Furthermore, ARPC spheroids express markers typical of pluripotent cells, such as stage-specific embryonic antigen 4 (SSEA4), secrete elevated levels of renin, and showed angiogenic properties. Notably, ARPCs isolated from urine of patients with IgA nephropathy form spheroids capable of recapitulating the characteristic IgA1 deposition observed in this disease. These findings represent a significant advancement in the field, opening up new avenues for regenerative medicine in the study of kidney development, mechanisms underlying renal disorders, and the development of regenerative therapies for kidney-related ailments.