Kidney Regeneration Research Articles

Development and intra-renal delivery of renal progenitor organoids for effective integration in vivo.

Renal progenitor organoids have been proposed as a source of tissue for kidney regeneration; however, their clinical translatability has not been demonstrated due to an inability to mass-produce comprehensive renal progenitor organoids and the lack of an effective intra-renal delivery platform that facilitates rapid integration into functionally meaningful sites. This study addresses these shortcomings. Human-induced pluripotent stem cells were differentiated into renal progenitor cells using an established protocol and aggregated using a novel assembly method to produce high yields of organoids. Organoids were encapsulated in collagen-based scaffolds for in vitro study and in vivo implantation into mouse renal cortex. In vitro, the organoids demonstrated sustained cell viability and renal structure maturation over time. In vivo delivered organoids showed rapid integration into host renal parenchyma while showing tubular and glomerular-like structure development and maturity markers. This proof-of-concept study presents many promising results, providing a system of renal organoid formation and delivery that may support the development of clinically translatable therapies and the advancement of in vitro renal organoid studies.

Multifunctional extracellular vesicles and edaravone-loaded scaffolds for kidney tissue regeneration by activating GDNF/RET pathway

With the severity of chronic kidney disease worldwide, strategies to recover renal function via tissue regeneration provide alternatives to kidney replacement therapy. To exclude side effects from direct cell transplantation, extracellular vesicles (EVs) are great substitutes representing paracrine cell signaling. To build three-dimensional structures for implantation into the 5/6 nephrectomy model by incorporating bioactive materials, including multifunctional EVs (mEVs), porous PMEZE/mEV scaffolds were developed in combination with edaravone (EDV; E) and mEV based on PMEZ scaffolds with PLGA (P), MH-RA (M), ECM (E), ZnO-ALA (Z). The oxygen free radical scavenger EDV was incorporated to induce tubular regeneration. mEVs were engineered to serve regenerative activities with a combination of two EVs from SDF-1α overexpressed tonsil-derived mesenchymal stem cells (sEVs) and intermediate mesoderm (IM) cells during differentiation into kidney progenitor cells (dEVs). mEVs displayed beneficial effects on regeneration by facilitating migration and inducing differentiation of surrounding stem cells, and EDV improved kidney function by regulating the GDNF/RET pathway and their downstream genes. The promotion of MSC recruitment was confirmed with sEV particles number dependently, and the regulation of the GDNF/RET pathway by the effect of EDV and its enhanced effect by mEVs were elucidated using in vitro analysis. The regeneration of tubules was additionally demonstrated through the increased expression of aquaporin-1 (AQP-1) and cadherin-16 (CDH16) for proximal tubules, and calbindin and PAX2 for distal tubules in the renal defect model. With these, structural regeneration and functional recovery were achieved with kidney regeneration in the 5/6 nephrectomy mice model.Graphical abstract

Selective Induction of Renal Interstitial Progenitor Cell Lineages from Human-Induced Pluripotent Stem Cells (hiPSCs) for Understanding of Mesangial and Erythropoietin (EPO)-Producing Cell Development and Kidney Regeneration

Selective Induction of Renal Interstitial Progenitor Cell Lineages from Human-Induced Pluripotent Stem Cells (hiPSCs) for Understanding of Mesangial and Erythropoietin (EPO)-Producing Cell Development and Kidney Regeneration

Deciphering Cellular Mechanisms in Cells of Renin Lineage-Mediated Kidney Regeneration under SGLT2 Inhibition

Deciphering Cellular Mechanisms in Cells of Renin Lineage-Mediated Kidney Regeneration under SGLT2 Inhibition

Nicotinamide Phosphoribosyltransferase (NAMPT) Improves Kidney Injury and Promotes Kidney Regeneration of Adult Zebrafish

Nicotinamide Phosphoribosyltransferase (NAMPT) Improves Kidney Injury and Promotes Kidney Regeneration of Adult Zebrafish

Targeted Pulsed Ultrasound of the Spleen Protects against AKI and CKD and Permits Kidney Regeneration

Targeted Pulsed Ultrasound of the Spleen Protects against AKI and CKD and Permits Kidney Regeneration

Expression levels and stoichiometry of Hnf1β, Emx2, Pax8 and Hnf4 influence direct reprogramming of induced renal tubular epithelial cells

Generation of induced renal epithelial cells (iRECs) from fibroblasts offers great opportunities for renal disease modeling and kidney regeneration. However, the low reprogramming efficiency of the current approach to generate iRECs has hindered potential therapeutic application and regenerative approach. This could be in part attributed to heterogeneous and unbalanced expression of reprogramming factors (RFs) Hnf1β (H1), Emx2 (E), Pax8 (P), and Hnf4α (H4) in transduced fibroblasts. Here, we establish an advanced retroviral vector system that expresses H1, E, P, and H4 in high levels and distinct ratios from bicistronic transcripts separated by P2A. Mouse embryonic fibroblasts (MEFs) harboring Cdh16-Cre; mT/mG allele are utilized to conduct iREC reprogramming via directly monitoring single cell fate conversion. Three sets of bicistronic RF combinations including H1E/H4P, H1H4/EP, and H1P/H4E have been generated to induce iREC reprogramming. Each of the RF combinations gives rise to distinct H1, E, P, and H4 expression levels and different reprogramming efficiencies. The desired H1E/H4P combination that results in high expression levels of RFs with balanced stoichiometry. substantially enhances the efficiency and quality of iRECs compared with transduction of separate H1, E, P, and H4 lentiviruses. We find that H1E/H4P-induced iRECs exhibit the superior features of renal tubular epithelial cells, as evidenced by expressing renal tubular-specific genes, possessing endocytotic arrogation activity and assembling into tubules along decellularized kidney scaffolds. This study establishes H1E/H4P cassette as a valuable platform for future iREC studies and regenerative medicine.

Spatial transcriptomics defines injury specific microenvironments and cellular interactions in kidney regeneration and disease

Kidney injury disrupts the intricate renal architecture and triggers limited regeneration, together with injury-invoked inflammation and fibrosis. Deciphering the molecular pathways and cellular interactions driving these processes is challenging due to the complex tissue structure. Here, we apply single cell spatial transcriptomics to examine ischemia-reperfusion injury in the mouse kidney. Spatial transcriptomics reveals injury-specific and spatially-dependent gene expression patterns in distinct cellular microenvironments within the kidney and predicts Clcf1-Crfl1 in a molecular interplay between persistently injured proximal tubule cells and their neighboring fibroblasts. Immune cell types play a critical role in organ repair. Spatial analysis identifies cellular microenvironments resembling early tertiary lymphoid structures and associated molecular pathways. Collectively, this study supports a focus on molecular interactions in cellular microenvironments to enhance understanding of injury, repair and disease.

How Stem and Progenitor Cells Can Affect Renal Diseases.

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.

Histological evaluation of renal progenitor/stem cells, renal mesenchymal stem-like cells, and endothelial progenitor cells in chronic kidney disease and end-stage renal disease, and molecular docking analysis of drug-receptor interactions

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are prevalent and debilitating conditions with a significant impact on patients' quality of life. In this study, we conducted a comprehensive investigation into the histological characteristics of renal progenitor/stem cells (RPCs), renal mesenchymal stem-like cells, and endothelial progenitor cells (EPCs) in CKD and ESRD patients. Additionally, we performed a molecular docking analysis to explore potential drug-receptor interactions involving common medications prescribed to CKD patients. Our histological examination revealed a noteworthy increase in the number of CD24- and CD133-positive cells in CKD and ESRD patients, representing RPCs. These cells are implicated in kidney repair and regeneration, underscoring their potential role in CKD management. Moreover, we observed an elevation in the number of EPCs within the kidneys of CKD and ESRD patients, suggesting a protective role of EPCs in kidney preservation. The molecular docking analysis unveiled intriguing insights into potential drug interventions. Notably, digoxin exhibited the highest in-silico binding affinity to numerous receptors associated with the functions of RPCs, renal mesenchymal stem-like cells, and EPCs, emphasizing the potential multifaceted effects of this cardiac glycoside in CKD patients. Other drugs, including apixaban, glimepiride, and glibenclamide, also displayed strong in-silico affinities to specific receptors, indicating their potential influence on various renal cell functions. In conclusion, this study provides valuable insights into the histological alterations in renal cell populations in CKD and ESRD patients and underscores the potential roles of RPCs and EPCs in kidney repair and preservation. The molecular docking analysis reveals the complex interactions between common drugs and renal cells, suggesting the need for further in-vitro and in-vivo research to fully understand these relationships. These findings contribute to our understanding of CKD and offer new avenues for research into potential therapeutic interventions.

Regenerative Role of Lrig1+ Cells in Kidney Repair.

In response to severe kidney injury, the kidney epithelium displays remarkable regenerative capabilities driven by adaptable resident epithelial cells. To date, it has been widely considered that the adult kidney lacks multipotent stem cells; thus, the cellular lineages responsible for repairing proximal tubule damage are incompletely understood. Leucine-rich repeats and immunoglobulin-like domains protein 1-expressing cells (Lrig1+ cells) have been identified as a long-lived cell in various tissues that can induce epithelial tissue repair. Therefore, we hypothesized that Lrig1+ cells participate in kidney development and tissue regeneration. We investigated the role of Lrig1+ cells in kidney injury using mouse models. The localization of Lrig1+ cells in the kidney was examined throughout mouse development. The function of Lrig1+ progeny cells in acute kidney injury repair was examined in vivo using a tamoxifen-inducible Lrig1-specific Cre recombinase-based lineage tracing in three different kidney injury mouse models. Additionally, we conducted single-cell RNA-sequencing to characterize the transcriptional signature of Lrig1+ cells and to trace their progeny. Lrig1+ cells were present during kidney development and contributed to formation of the proximal tubule and collecting duct structures in mature mouse kidneys. In three-dimensional culture, single Lrig1+ cells demonstrated long-lasting propagation and differentiated into the proximal tubule and collecting duct lineages. These Lrig1+ proximal tubule cells highly expressed progenitor-like and quiescence-related genes, giving rise to a novel cluster of cells with regenerative potential in adult kidneys. Moreover, these long-lived Lrig1+ cells expanded and repaired damaged proximal tubules in response to three types of acute kidney injury in mice. These findings highlight the critical role of Lrig1+ cells in kidney regeneration.

Kidney Injury: Focus on Molecular Signaling Pathways.

Acute kidney injury (AKI) is a syndrome in which kidney function reduces suddenly. This syndrome which includes both structural changes and loss of function may lead to chronic kidney disease (CKD). Kidney regeneration capacity depends on the cell type and severity of the injury. However, novel studies indicated that regeneration mostly relies on endogenous tubular cells that survive after AKI. Regenerative pharmacology requires a great knowledge of fundamental processes involved in the development and endogenous regeneration, leading to a necessity for investigating related signaling molecules in this process. Regulatory non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are currently known as critical regulators of gene expression in various cellular processes, and this regulatory function is also observed in nephrotic tissue, following damaging insults, which may promote or inhibit the progression of damage. Thus, studying signaling molecules and pathways involved in renal injury and repair results in a comprehensive prospect of these processes. Moreover, these studies can lead to new opportunities for discovering and enhancing therapeutic approaches to renal diseases. Herein, we review studies dealing with the role of different signaling pathways involved in renal injury. Besides, we discuss how some signaling pathways are useful for the repair process following AKI.

Molecular mechanism of BMP signal control by Twisted gastrulation

Twisted gastrulation (TWSG1) is an evolutionarily conserved secreted glycoprotein which controls signaling by Bone Morphogenetic Proteins (BMPs). TWSG1 binds BMPs and their antagonist Chordin to control BMP signaling during embryonic development, kidney regeneration and cancer. We report crystal structures of TWSG1 alone and in complex with a BMP ligand, Growth Differentiation Factor 5. TWSG1 is composed of two distinct, disulfide-rich domains. The TWSG1 N-terminal domain occupies the BMP type 1 receptor binding site on BMPs, whereas the C-terminal domain binds to a Chordin family member. We show that TWSG1 inhibits BMP function in cellular signaling assays and mouse colon organoids. This inhibitory function is abolished in a TWSG1 mutant that cannot bind BMPs. The same mutation in the Drosophila TWSG1 ortholog Tsg fails to mediate BMP gradient formation required for dorsal-ventral axis patterning of the early embryo. Our studies reveal the evolutionarily conserved mechanism of BMP signaling inhibition by TWSG1.

Hold the salt for kidney regeneration.

The macula densa (MD) is a distinct cluster of approximately 20 specialized kidney epithelial cells that constitute a key component of the juxtaglomerular apparatus. Unlike other renal tubular epithelial cell populations with functions relating to reclamation or secretion of electrolytes and solutes, the MD acts as a cell sensor, exerting homeostatic actions in response to sodium and chloride changes within the tubular fluid. Electrolyte flux through apical sodium transporters in MD cells triggers release of paracrine mediators, affecting blood pressure and glomerular hemodynamics. In this issue of the JCI, Gyarmati and authors explored a program of MD that resulted in activation of regeneration pathways. Notably, regeneration was triggered by feeding mice a low-salt diet. Furthermore, the MD cells showed neuron-like properties that may contribute to their regulation of glomerular structure and function. These findings suggest that dietary sodium restriction and/or targeting MD signaling might attenuate glomerular injury.

Long-term expandable mouse and human-induced nephron progenitor cells enable kidney organoid maturation and modeling of plasticity and disease

Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here, manipulation of p38 and YAP activity allowed for long-term clonal expansion of primary mouse and human NPCs and induced NPCs (iNPCs) from human pluripotent stem cells (hPSCs). Molecular analyses demonstrated that cultured iNPCs closely resemble primary human NPCs. iNPCs generated nephron organoids with minimal off-target cell types and enhanced maturation of podocytes relative to published human kidney organoid protocols. Surprisingly, the NPC culture medium uncovered plasticity in human podocyte programs, enabling podocyte reprogramming to an NPC-like state. Scalability and ease of genome editing facilitated genome-wide CRISPR screening in NPC culture, uncovering genes associated with kidney development and disease. Further, NPC-directed modeling of autosomal-dominant polycystic kidney disease (ADPKD) identified a small-molecule inhibitor of cystogenesis. These findings highlight a broad application for the reported iNPC platform in the study of kidney development, disease, plasticity, and regeneration.

Loss of SAV1 in Kidney Proximal Tubule Induces Maladaptive Repair after Ischemia and Reperfusion Injury.

Kidney ischemia and reperfusion injury (IRI) is a significant contributor to acute kidney injury (AKI), characterized by tubular injury and kidney dysfunction. Salvador family WW domain containing protein 1 (SAV1) is a key component of the Hippo pathway and plays a crucial role in the regulation of organ size and tissue regeneration. However, whether SAV1 plays a role in kidney IRI is not investigated. In this study, we investigated the role of SAV1 in kidney injury and regeneration following IRI. A proximal tubule-specific knockout of SAV1 in kidneys (SAV1ptKO) was generated, and wild-type and SAV1ptKO mice underwent kidney IRI or sham operation. Plasma creatinine and blood urea nitrogen were measured to assess kidney function. Histological studies, including periodic acid-Schiff staining and immunohistochemistry, were conducted to assess tubular injury, SAV1 expression, and cell proliferation. Western blot analysis was employed to assess the Hippo pathway-related and proliferation-related proteins. SAV1 exhibited faint expression in the proximal tubules and was predominantly expressed in the connecting tubule to the collecting duct. At 48 h after IRI, SAV1ptKO mice continued to exhibit severe kidney dysfunction, compared to attenuated kidney dysfunction in wild-type mice. Consistent with the functional data, severe tubular damage induced by kidney IRI in the cortex was significantly decreased in wild-type mice at 48 h after IRI but not in SAV1ptKO mice. Furthermore, 48 h after IRI, the number of Ki67-positive cells in the cortex was significantly higher in wild-type mice than SAV1ptKO mice. After IRI, activation and expression of Hippo pathway-related proteins were enhanced, with no significant differences observed between wild-type and SAV1ptKO mice. Notably, at 48 h after IRI, protein kinase B activation (AKT) was significantly enhanced in SAV1ptKO mice compared to wild-type mice. This study demonstrates that SAV1 deficiency in the kidney proximal tubule worsens the injury and delays kidney regeneration after IRI, potentially through the overactivation of AKT.

Decellularized kidney extracellular matrix-based hydrogels for renal tissue engineering

Kidney regeneration is hindered by the limited pool of intrinsic reparative cells. Advanced therapies targeting renal regeneration have the potential to alleviate the clinical and financial burdens associated with kidney disease. Delivery systems for cells, extracellular vesicles, or growth factors aimed at enhancing regeneration can benefit from vehicles enabling targeted delivery and controlled release. Hydrogels, optimized to carry biological cargo while promoting regeneration, have emerged as promising candidates for this purpose. This study aims to develop a hydrogel from decellularized kidney extracellular matrix (DKECM) and explore its biocompatibility as a biomaterial for renal regeneration. The resulting hydrogel crosslinks with temperature and exhibits a high concentration of extracellular matrix. The decellularization process efficiently removes detergent residues, yielding a pathogen-free biomaterial that is non-hemolytic and devoid of α-gal epitope. Upon interaction with macrophages, the hydrogel induces differentiation into both pro-inflammatory and anti-inflammatory phenotypes, suggesting an adequate balance to promote biomaterial functionality in vivo. Renal progenitor cells encapsulated in the DKECM hydrogel demonstrate higher viability and proliferation than in commercial collagen-I hydrogels, while also expressing tubular cells and podocyte markers in long-term culture.Overall, the injectable biomaterial derived from porcine DKECM is anticipated to elicit minimal host reaction while fostering progenitor cell bioactivity, offering a potential avenue for enhancing renal regeneration in clinical settings. Statement of significanceThe quest to improve treatments for kidney disease is crucial, given the challenges faced by patients on dialysis or waiting for transplants. Exciting new therapies combining biomaterials with cells can revolutionize kidney repair. In this study, researchers created a hydrogel from pig kidney. This gel could be used to deliver cells and other substances that help in kidney regeneration. Despite coming from pigs, it's safe for use in humans, with no harmful substances and reduced risk of immune reactions. Importantly, it promotes a balanced healing response in the body. This research not only advances our knowledge of kidney repair but also offers hope for more effective treatments for kidney diseases.

Kidney Mesenchymal Stem Cell Differentiation: Effect of Scaffold and Basic Fibroblast Growth Factor.

Background: Chronic kidney disease (CKD) poses a global health challenge, and it needs alternative therapeutic approaches for patients with end-stage renal disease (ESRD). Although organ transplantation is effective, it faces challenges such as declining quality of life, immunological responses, transplant rejection, and donor shortages. Tissue engineering, by using suitable scaffolds, cells, and growth factors, emerges as a promising treatment option for kidney regeneration. Experiment: We precisely decellularized scaffold, derived from rat kidneys while maintaining its native three-dimensional (3D) architecture. The efficiency of decellularization was evaluated through histological examinations, including hematoxylin and eosin, periodic acid-Schiff, and DAPI staining, as well as scanning electron microscopy. The scaffolds were then recellularized with kidney mesenchymal stem cells (kMSCs), and their adhesion, proliferation, and differentiation were assessed over 1, 2, and 3 weeks. The expression of specific renal markers, including Wt-1, ZO-1, AQP-1, and ANG-1, was examined through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in monolayer and 3D cultures. Results: The infiltration rate of cells into the scaffold increased in a time-dependent manner, and the expression of specific renal markers significantly increased, demonstrating successful differentiation of kMSCs within the scaffold. The application of basic fibroblast growth factor (bFGF) could intensify the expression of kidney-specific genes. Conclusions: The study highlighted the importance of preserving the 3D architecture of the scaffold during decellularization to achieve optimal cellular responses. Moreover, the capacity of mesenchymal stem cells in recellularized scaffolds facilitated tissue regeneration.

The redox-sensitive GSK3β is a key regulator of glomerular podocyte injury in type 2 diabetic kidney disease

Emerging evidence suggests that GSK3β, a redox-sensitive transducer downstream of insulin signaling, acts as a convergent point for myriad pathways implicated in kidney injury, repair, and regeneration. However, its role in diabetic kidney disease remains controversial. In cultured glomerular podocytes, exposure to a milieu of type 2 diabetes elicited prominent signs of podocyte injury and degeneration, marked by loss of homeostatic marker proteins like synaptopodin, actin cytoskeleton disruption, oxidative stress, apoptosis, and stress-induced premature senescence, as shown by increased staining for senescence-associated β-galactosidase activity, amplified formation of γH2AX foci, and elevated expression of mediators of senescence signaling, like p21 and p16INK4A. These degenerative changes coincided with GSK3β hyperactivity, as evidenced by GSK3β overexpression and reduced inhibitory phosphorylation of GSK3β, and were averted by tideglusib, a highly-selective small molecule inhibitor of GSK3β. In agreement, post-hoc analysis of a publicly-available glomerular transcriptomics dataset from patients with type 2 diabetic nephropathy revealed that the curated diabetic nephropathy-related gene set was enriched in high GSK3β expression group. Mechanistically, GSK3β-modulated nuclear factor Nrf2 signaling is involved in diabetic podocytopathy, because GSK3β knockdown reinforced Nrf2 antioxidant response and suppressed oxidative stress, resulting in an improvement in podocyte injury and senescence. Conversely, ectopic expression of the constitutively active mutant of GSK3β impaired Nrf2 antioxidant response and augmented oxidative stress, culminating in an exacerbated diabetic podocyte injury and senescence. Moreover, IRS-1 was found to be a cognate substrate of GSK3β for phosphorylation at IRS-1S332, which negatively regulates IRS-1 activity. GSK3β hyperactivity promoted IRS-1 phosphorylation, denoting a desensitized insulin signaling. Consistently, in vivo in db/db mice with diabetic nephropathy, GSK3β was hyperactive in glomerular podocytes, associated with IRS-1 hyperphosphorylation, impaired Nrf2 response and premature senescence. Our finding suggests that GSK3β is likely a novel therapeutic target for treating type 2 diabetic glomerular injury.

Advances in the Treatment of Kidney Disorders using Mesenchymal Stem Cells.

Renal disease is a medical condition that poses a potential threat to the life of an individual and is related to substantial morbidity and mortality rates in clinical environments. The aetiology of this condition is influenced by multiple factors, and its incidence tends to increase with progressive aging. Although supportive therapy and kidney transplantation have potential advantages, they also have limitations in terms of mitigating the progression of KD. Despite significant advancements in the domain of supportive therapy, mortality rates in patients continue to increase. Due to their ability to self-renew and multidirectionally differentiate, stem cell therapy has been shown to have tremendous potential in the repair of the diseased kidney. MSCs (Mesenchymal stem cells) are a cell population that is extensively distributed and can be located in various niches throughout an individual's lifespan. The cells in question are characterised by their potential for indefinite replication and their aptitude for undergoing differentiation into fully developed cells of mesodermal origin under laboratory conditions. It is essential to emphasize that MSCs have demonstrated a favorable safety profile and efficacy as a therapeutic intervention for renal diseases in both preclinical as well as clinical investigations. MSCs have been found to slow the advancement of kidney disease, and this impact is thought to be due to their control over a number of physiological processes, including immunological response, tubular epithelial- mesenchymal transition, oxidative stress, renal tubular cell death, and angiogenesis. In addition, MSCs demonstrate recognised effectiveness in managing both acute and chronic kidney diseases via paracrine pathways. The proposal to utilise a therapy that is based on stem-cells as an effective treatment has been put forward in search of discovering novel therapies to promote renal regeneration. Preclinical researchers have demonstrated that various types of stem cells can provide advantages in acute and chronic kidney disease. Moreover, preliminary results from clinical trials have suggested that these interventions are both safe and well-tolerated. This manuscript provides a brief overview of the potential renoprotective effects of stem cell-based treatments in acute as well as chronic renal dysfunction. Furthermore, the mechanisms that govern the process of kidney regeneration induced by stem cells are investigated. This article will examine the therapeutic approaches that make use of stem cells for the treatment of kidney disorders. The analysis will cover various cellular sources that have been utilised, potential mechanisms involved, and the outcomes that have been achieved so far.