Regenerative pharmacology for the treatment of acute kidney injury: Skeletal muscle stem/progenitor cells for renal regeneration?

2016 ◽  
Vol 113 ◽  
pp. 802-807 ◽  
Author(s):  
Egle Pavyde ◽  
Arvydas Usas ◽  
Romaldas Maciulaitis
Keyword(s):  
Skeletal Muscle ◽  
Acute Kidney Injury ◽  
Progenitor Cells ◽  
Kidney Injury ◽  
Renal Regeneration

scholarly journals Skeletal Muscle-Derived Stem/Progenitor Cells: A Potential Strategy for the Treatment of Acute Kidney Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Egle Pavyde ◽  
Romaldas Maciulaitis ◽  
Mykolas Mauricas ◽  
Gintaras Sudzius ◽  
Ernesta Ivanauskaite Didziokiene ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Acute Kidney Injury ◽  
Progenitor Cells ◽  
Therapeutic Potential ◽  
Kidney Injury ◽  
Population Doubling ◽  
Population Doubling Time ◽  
Isolation Technique ◽  
Time Flow ◽  
Potential Strategy

Skeletal muscle-derived stem/progenitor cells (MDSPCs) have been thoroughly investigated and already used in preclinical studies. However, therapeutic potential of MDSPCs isolated using preplate isolation technique for acute kidney injury (AKI) has not been evaluated. We aimed to characterize rat MDSPCs, compare them with bone marrow mesenchymal stem cells (BM-MSCs), and evaluate the feasibility of MDSPCs therapy for gentamicin-induced AKI in rats. We have isolated and characterized rat MDSPCs and BM-MSCs. Characteristics of rat BM-MSCs and MDSPCs were assessed by population doubling time, flow cytometry, immunofluorescence staining, RT-PCR, and multipotent differentiation capacity. Gentamicin-induced AKI model in rat was used to examine MDSPCs therapeutic effect. Physiological and histological kidney parameters were determined. MDSPCs exhibited similar immunophenotype, stem cell gene expression, and multilineage differentiation capacities as BM-MSCs, but they demonstrated higher proliferation rate. Single intravenous MDSPCs injection accelerated functional and morphological kidney recovery, as reflected by significantly lower serum creatinine levels, renal injury score, higher urinary creatinine, and GFR levels. PKH-26-labeled MDSPCs were identified within renal cortex 1 and 2 weeks after cell administration, indicating MDSPCs capacity to migrate and populate renal tissue. In conclusion, MDSPCs are capable of mediating functional and histological kidney recovery and can be considered as potential strategy for AKI treatment.

scholarly journals Endothelial progenitor cells-derived exosomal microRNA-21-5p alleviates sepsis-induced acute kidney injury by inhibiting RUNX1 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Yue Zhang ◽  
Hongdong Huang ◽  
Wenhu Liu ◽  
Sha Liu ◽  
Xue Yan Wang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Endothelial Glycocalyx ◽  
Endothelial Progenitor ◽  
Marker Proteins ◽  
Related Transcription Factor

AbstractThe role of microRNA-21-5p (miR-21-5p) in sepsis-induced acute kidney injury (AKI) has been seldom discussed. Therefore, the objective of this present study was to investigate the mechanism of endothelial progenitor cells-derived exosomes (EPCs-exos) in sepsis-induced AKI via miR-21-5p/runt-related transcription factor 1 (RUNX1) axis. miR-21-5p was downregulated and RUNX1 was upregulated in the kidney of cecal ligation and puncture (CLP) rats, and miR-21-5p targeted RUNX1. Elevation of miR-21-5p improved renal function and renal tissue pathological damage, attenuated serum inflammatory response, as well as reduced apoptosis and oxidative stress response in renal tissues, and regulated endothelial glycocalyx damage marker proteins syndecan-1 and heparanase-1 in CLP rats. Overexpression of RUNX1 abolished the impacts of elevated miR-21-5p in CLP rats. Also, EPCs-exos upregulated miR-21-5p expression, and functioned similar to elevation of miR-21-5p for CLP rats. Downregulating miR-21-5p partially reversed the effects of EPCs-exos on sepsis-induced AKI. Collectively, our study suggests that EPCs release miR-21-5p-containing exosomes to alleviate sepsis-induced AKI through RUNX1 silencing.

scholarly journals P0524PERICYTE IS ESSENTIAL FOR RENAL TUBULAR CELL REGENERATION AFTER ACUTE KIDNEY INJURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yu-Hsiang Chou ◽  
YU-HAN SHAO ◽  
SHUEI-LIONG LIN
Keyword(s):  
Acute Kidney Injury ◽  
Growth Factor ◽  
Renal Injury ◽  
Renal Fibrosis ◽  
Kidney Injury ◽  
Renal Recovery ◽  
Renal Tubular Cell ◽  
Inflammatory Factor ◽  
Control Groups ◽  
Renal Regeneration

Abstract Background and Aims Pericyte-myofibroblast transition is activated after acute kidney injury (AKI) and is the major mechanism of ensuing chronic kidney disease (CKD). Nevertheless, the role of pericyte in renal regeneration after AKI has not been deeply investigated. Many studies have shown that pericyte can secret growth factors such as fibroblast growth factor 1 and 7 (FGF-1, FGF-7) and is essential for structure support and vascular integrity in normal kidney. We supposed that the ablation or inhibition of pericytes during AKI would retard renal repair. Method Our study demonstrated that activated pericytes/myofibroblast was beneficial for renal regeneration after AKI. We here performed pericyte ablation and pericyte inhibition after ischemia-reperfusion renal injury by using transgenic mice such as Gli1-CreERT2;iDTR mice and blockade of platelet-derived growth factor receptor β (PDGFRβ), respectively. Results Renal injury was more severe and renal recovery was worse in groups of pericyte ablation or inhibition compared to control groups. Ki67 positive tubular cells which indicated renal regeneration were much more in control groups than that in groups of pericyte ablation or inhibition. We also found higher macrophage number as well as higher inflammatory factor including tumor necrosis factor-α and interleukin-1β which indicated more severe inflammation in groups of pericyte ablation or inhibition. Conclusion These studies suggest that pericytes play a beneficial role during renal recovery after AKI. These findings delineate the adequate timing when we target on pericyte/myofibroblast to ameliorate renal fibrosis and avoid to impede renal regeneration at the same time. Further research is still needed to clarify the change of specific gene and signalling pathway after pericyte ablation or inhibition. These are promising findings that provide opportunities to develop new targets to promote AKI recovery and to ameliorate renal fibrosis.

scholarly journals Class I HDAC activity is required for renal protection and regeneration after acute kidney injury

2014 ◽  
Vol 307 (3) ◽  
pp. F303-F316 ◽  
Author(s):  
Jinhua Tang ◽  
Yanli Yan ◽  
Ting C. Zhao ◽  
Rujun Gong ◽  
George Bayliss ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Development ◽  
Kidney Injury ◽  
Class I ◽  
Nuclear Antigen ◽  
Renal Tubular Cell ◽  
Renal Protection ◽  
Hdac Activity ◽  
Renal Regeneration ◽  
Class I Hdacs

Activation of histone deacetylases (HDACs) is required for renal epithelial cell proliferation and kidney development. However, their role in renal tubular cell survival and regeneration after acute kidney injury (AKI) remains unclear. In this study, we demonstrated that all class I HDAC isoforms (1, 2, 3, and 8) were expressed in the renal epithelial cells of the mouse kidney. Inhibition of class I HDACs with MS-275, a highly selective inhibitor, resulted in more severe tubular injury in the mouse model of AKI induced by folic acid or rhabdomyolysis, as indicated by worsening renal dysfunction, increased neutrophil gelatinase-associated lipocalin expression, and enhanced apoptosis and caspase-3 activation. Blocking class I HDAC activity also impaired renal regeneration as evidenced by decreased expression of renal Pax-2, vimentin, and proliferating cell nuclear antigen. Injury to the kidney is accompanied by increased phosphorylation of epidermal growth factor receptor (EGFR), signal transducers and activators of transcription 3 (STAT3), and Akt. Inhibition of class I HDACs suppressed EGFR phosphorylation as well as reduced its expression. MS-275 was also effective in inhibiting STAT3 and Akt phosphorylation, but this treatment did not affect their expression levels. Taken together, these data suggest that the class I HDAC activity contributes to renal protection and functional recovery and is required for renal regeneration after AKI. Furthermore, renal EGFR signaling is subject to regulation by this class of HDACs.

scholarly journals SaO032PAPILLARY RENAL CELL CARCINOMA ORIGINATES FROM A POPULATION OF RENAL PROGENITOR CELLS AND IS PROMOTED BY ACUTE KIDNEY INJURY

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i328-i328
Author(s):  
Anna Peired ◽  
Giulia Antonelli ◽  
Maria Lucia Angelotti ◽  
Alessandro Sisti ◽  
Marco Allinovi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Acute Kidney Injury ◽  
Cell Carcinoma ◽  
Progenitor Cells ◽  
Renal Cell ◽  
Kidney Injury ◽  
Renal Progenitor Cells ◽  
Renal Progenitor

Renal disorders

2019 ◽  
pp. 341-346
Author(s):  
Carl Waldmann ◽  
Andrew Rhodes ◽  
Neil Soni ◽  
Jonathan Handy
Keyword(s):  
Acute Kidney Injury ◽  
Volume Expansion ◽  
Kidney Injury ◽  
Renal Perfusion ◽  
Oxygen Radical ◽  
Renal Physiology ◽  
Renal Metabolism ◽  
Renal Disorders ◽  
Renal Regeneration ◽  
Radical Damage

This chapter discusses renal disorders and includes discussion on prevention of acute kidney injury, including optimizing renal perfusion with the use of volume expansion, inotropic, vasopressor, and vasodilator medications; modulation of renal physiology, including renal metabolism, tubular obstruction, oxygen radical damage, and renal regeneration and repair. This chapter also discusses the diagnosis of acute kidney injury, including parameters of glomerular function, urine analyses, biomarkers, ultrasound, autoimmune profiling, and renal biopsy.

Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells

2020 ◽  
Vol 12 (536) ◽  
pp. eaaw6003 ◽  
Author(s):  
Anna Julie Peired ◽  
Giulia Antonelli ◽  
Maria Lucia Angelotti ◽  
Marco Allinovi ◽  
Francesco Guzzi ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Progenitor Cells ◽  
Renal Cell ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Lineage Tracing ◽  
Cell Of Origin ◽  
Renal Progenitor Cells ◽  
Renal Progenitor

Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis and polyploidization, leading to cell function alterations that may potentially drive cancer development. Here, we show that acute kidney injury (AKI) increased the risk for papillary renal cell carcinoma (pRCC) development and tumor relapse in humans as confirmed by data collected from several single-center and multicentric studies. Lineage tracing of tubular epithelial cells (TECs) after AKI induction and long-term follow-up in mice showed time-dependent onset of clonal papillary tumors in an adenoma-carcinoma sequence. Among AKI-related pathways, NOTCH1 overexpression in human pRCC associated with worse outcome and was specific for type 2 pRCC. Mice overexpressing NOTCH1 in TECs developed papillary adenomas and type 2 pRCCs, and AKI accelerated this process. Lineage tracing in mice identified single renal progenitors as the cell of origin of papillary tumors. Single-cell RNA sequencing showed that human renal progenitor transcriptome showed similarities to PT1, the putative cell of origin of human pRCC. Furthermore, NOTCH1 overexpression in cultured human renal progenitor cells induced tumor-like 3D growth. Thus, AKI can drive tumorigenesis from local tissue progenitor cells. In particular, we find that AKI promotes the development of pRCC from single progenitors through a classical adenoma-carcinoma sequence.

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