scholarly journals Stem Cell-Based Cell Therapy for Glomerulonephritis

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Meiling Jin ◽  
Yuansheng Xie ◽  
Qinggang Li ◽  
Xiangmei Chen

Glomerulonephritis (GN), characterized by immune-mediated inflammatory changes in the glomerular, is a common cause of end stage renal disease. Therapeutic options for glomerulonephritis applicable to all cases mainly include symptomatic treatment and strategies to delay progression. In the attempt to yield innovative interventions fostering the limited capability of regeneration of renal tissue after injury and the uncontrolled pathological process by current treatments, stem cell-based therapy has emerged as novel therapy for its ability to inhibit inflammation and promote regeneration. Many basic and clinical studies have been performed that support the ability of various stem cell populations to ameliorate glomerular injury and improve renal function. However, there is a long way before putting stem cell-based therapy into clinical practice. In the present article, we aim to review works performed with respect to the use of stem cell of different origins in GN, and to discuss the potential mechanism of therapeutic effect and the challenges for clinical application of stem cells.

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Shinya Yokote ◽  
Shuichiro Yamanaka ◽  
Takashi Yokoo

Recent studies have reported on techniques to mobilize and activate endogenous stem-cells in injured kidneys or to introduce exogenous stem cells for tissue repair. Despite many recent advantages in renal regenerative therapy, chronic kidney disease (CKD) remains a major cause of morbidity and mortality and the number of CKD patients has been increasing. When the sophisticated structure of the kidneys is totally disrupted by end stage renal disease (ESRD), traditional stem cell-based therapy is unable to completely regenerate the damaged tissue. This suggests that whole organ regeneration may be a promising therapeutic approach to alleviate patients with uncured CKD. We summarize here the potential of stem-cell-based therapy for injured tissue repair andde novowhole kidney regeneration. In addition, we describe the hurdles that must be overcome and possible applications of this approach in kidney regeneration.


2020 ◽  
Author(s):  
wanfu BAI ◽  
Qing Liu ◽  
Hong Chang ◽  
Quanli Liu ◽  
Chen Gao ◽  
...  

Abstract Background: Renal fibrosis is a pathological process of progression from chronic kidney disease to end-stage renal disease, which threaten human health. Amygdalus mongolica is a traditional Chinese medicine, and our previous studies demonstrated that the n-butanol extract (BUT) and amygdalin extract (AMY) from its seeds, which are effective components of A. mongolica, can prevent renal fibrosis (RF). The present study was to investigate the exact mechanism of the protective effect of A. mongolica on RF. Methods: The RF rat model was established through unilateral ureteral obstruction (UUO). Biochemical indicators were measured, combined with histopathology of renal tissue, to evaluate the anti-RF effects of the extracts of A. mongolica. A serum metabonomic method based on UPLC-QTOF-MS was used to clarify the changes in the metabolic profile among the different groups. Results: We found that tubulointerstitial damage and fibrosis were significantly improved, metabolic perturbations were restored after treatment with BUT and AMY. Thirty-eight metabolites associated with RF progression and related to the regulation of arginine and proline metabolism, nicotinate and nicotinamide metabolism, histidine metabolism and pentose and glucuronate interconversions were identified. They were restored to levels similar to those observed in controls by treatment with AMY and BUT. Moreover, no significant differences in efficacy were observed between the BUT and AMY groups. Conclusions: The results demonstrated that antifibrotic effects of A. mongolica in rats with RF. It was the first to reveal the potential mechanisms of the renoprotective effects after treatment with BUT and AMY from A. mongolica.


2015 ◽  
Vol 2 (1) ◽  
pp. 20-27 ◽  
Author(s):  
Yang Liu ◽  
Sydney C.W. Tang

Background: Diabetic nephropathy (DN) represents the leading cause of end-stage renal disease. Current therapeutic strategies for DN are very limited, and none of them can stop end-stage renal disease progression. Stem cell-based therapy showed encouraging outcomes in kidney disease, including experimental DN. Summary: Both podocytes and proximal tubular epithelial cells play key roles in the pathogenesis of DN and, accordingly, could be regarded as treatment targets. Multiple kinds of stem cells contribute to the regeneration of the injured kidney, including embryonic stem cells (ESCs), mesenchymal stem cells, and induced pluripotent stem cells (iPSCs). Stem cells exert reparatory effects mainly by homing to injured sites, directing differentiation, paracrine action, and immunoregulation. However, poor survival after transplantation under diabetic conditions and unsatisfactory animal models of advanced DN are major obstacles for achieving an efficacious therapeutic effect from stem cell transplantation. Recently, remarkable progress has been made both in the direct differentiation of human ESCs and iPSCs into renal cells and in the generation of tissue- and patient-specific iPSCs, offering a powerful tool to investigate DN mechanisms and to identify the ideal candidate cell for future clinical application. Key Message: This review provides updated information on recent progress and limitations of stem cell-based therapy for DN.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3060
Author(s):  
Shin-Ruen Yang ◽  
Szu-Chun Hung ◽  
Lichieh Julie Chu ◽  
Kuo-Feng Hua ◽  
Chyou-Wei Wei ◽  
...  

Renal tubulointerstitial lesions (TILs), a common pathologic hallmark of chronic kidney disease that evolves to end-stage renal disease, is characterized by progressive inflammation and pronounced fibrosis of the kidney. However, current therapeutic approaches to treat these lesions remain largely ineffectual. Previously, we demonstrated that elevated IL-36α levels in human renal tissue and urine are implicated in impaired renal function, and IL-36 signaling enhances activation of NLRP3 inflammasome in a mouse model of TILs. Recently, we synthesized NSC828779, a salicylanilide derivative (protected by U.S. patents with US 8975255 B2 and US 9162993 B2), which inhibits activation of NF-κB signaling with high immunomodulatory potency and low IC50, and we hypothesized that it would be a potential drug candidate for renal TILs. The current study validated the therapeutic effects of NSC828779 on TILs using a mouse model of unilateral ureteral obstruction (UUO) and relevant cell models, including renal tubular epithelial cells under mechanically induced constant pressure. Treatment with NSC828779 improved renal lesions, as demonstrated by dramatically reduced severity of renal inflammation and fibrosis and decreased urinary cytokine levels in UUO mice. This small molecule specifically inhibits the IL-36α/NLRP3 inflammasome pathway. Based on these results, the beneficial outcome represents synergistic suppression of both the IL-36α-activated MAPK/NLRP3 inflammasome and STAT3- and Smad2/3-dependent fibrogenic signaling. NSC828779 appears justified as a new drug candidate to treat renal progressive inflammation and fibrosis.


2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Zhilong Zhang ◽  
Xinju Li ◽  
Liang Liu ◽  
Jiya Sun ◽  
Xu Wang ◽  
...  

Background. Diabetic nephropathy is a common and serious complication of diabetes and a major cause of end-stage renal disease. Tiaolipiwei acupuncture is a safe treatment approach that may be effective for lowering albuminuria in diabetic nephropathy. Yet, the exact mechanisms of this therapeutic effect are unclear. Methods. A rodent model of type 2 diabetic nephropathy (T2DN) was induced by a high-fat diet combined with low-dose streptozotocin. T2DN rats were treated with Tiaolipiwei acupuncture (ACU) for 4, 8, or 12 weeks. At the end of treatment, urinary and blood samples were collected for analysis. Transmission electron microscopy was used to observe morphological changes, and protein expression levels of nephrin, CD2AP, podocalyxin, and desmin were quantified in renal tissue. Results. Compared to the T2DN groups, the T2DN + ACU groups showed significant improvements in 24-hour urinary protein, serum urea, cholesterol, and triglycerides at all time points. ACU treatment also improved the density of slit diaphragms. Simultaneously, ACU promoted the renal expression of nephrin, CD2AP, and podocalyxin and decreased the expression of desmin. Conclusion. Our study suggests that Tiaolipiwei acupuncture ameliorates podocyte lesions to reduce albuminuria and prevent the progression of T2DN in a rat model.


Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 778
Author(s):  
Carolina Amaral Bueno Azevedo ◽  
Regiane Stafim da Cunha ◽  
Carolina Victoria Cruz Junho ◽  
Jessica Verônica da Silva ◽  
Andréa N. Moreno-Amaral ◽  
...  

Cardiorenal syndrome (CRS) is described as primary dysfunction in the heart culminating in renal injury or vice versa. CRS can be classified into five groups, and uremic toxin (UT) accumulation is observed in all types of CRS. Protein-bound uremic toxin (PBUT) accumulation is responsible for permanent damage to the renal tissue, and mainly occurs in CRS types 3 and 4, thus compromising renal function directly leading to a reduction in the glomerular filtration rate (GFR) and/or subsequent proteinuria. With this decrease in GFR, patients may need renal replacement therapy (RRT), such as peritoneal dialysis (PD). PD is a high-quality and home-based dialysis therapy for patients with end-stage renal disease (ESRD) and is based on the semi-permeable characteristics of the peritoneum. These patients are exposed to factors which may cause several modifications on the peritoneal membrane. The presence of UT may harm the peritoneum membrane, which in turn can lead to the formation of extracellular vesicles (EVs). EVs are released by almost all cell types and contain lipids, nucleic acids, metabolites, membrane proteins, and cytosolic components from their cell origin. Our research group previously demonstrated that the EVs can be related to endothelial dysfunction and are formed when UTs are in contact with the endothelial monolayer. In this scenario, this review explores the mechanisms of EV formation in CRS, uremia, the peritoneum, and as potential biomarkers in peritoneal dialysis.


2021 ◽  
Vol 28 ◽  
Author(s):  
Ming Yang ◽  
Xi Wang ◽  
Yachun Han ◽  
Chenrui Li ◽  
Ling Wei ◽  
...  

: Diabetic nephropathy (DN) is one of the most common complications of diabetes and the main cause of end-stage renal disease (ESRD). The inflammatory response plays a key role in the pathological process of DN. As the most deeply studied inflammasome, NLRP3 should not be overlooked in DN. Its abnormal activation accelerates DN progression. In this review, we summarize our understanding of the structural composition and activation factors of the NLRP3 inflammasome. Moreover, the relationship between NLRP3 inflammasome activation, and the potential of the NLRP3 inflammasome as a therapeutic target for DN will also be discussed.


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