Mesenchymal Stem Cells Contribute to Improvement of Renal Function in a Canine Kidney Injury Model

Lee, Seungjun; Ryu, Min-Ok; Seo, Min–Soo; Park, Sang‐Bum; Ahn, Ji Yun; Han, Sei-Myoung; Kang, Kyung‐Sun; Bhang, Dong-Ha; Youn, Hwa‐Young

doi:10.21873/invivo.11177

Cited by 20 publications

(20 citation statements)

References 38 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These findings suggest that MSCs can protect against AKI through the anti-inflammatory activation of macrophages, which assists in the recovery from tubular injury. MSCs have also been shown to contribute to improved renal function in an in vivo canine acute kidney injury model, by decreasing BUN and creatinine levels and recovering renal lesions [42]. Another study has suggested that MSCs treatment improves glomerular filtration, renal function, and alleviates oxidative stress-induced cell senescence and inflammation and increases the proliferation of kidney cells in an ischemia/reperfusion injury (IRI)-induced acute kidney injury model [43].…”

Section: Msc-based Therapy For Kidney Diseasementioning

confidence: 99%

Potential and Therapeutic Efficacy of Cell-based Therapy Using Mesenchymal Stem Cells for Acute/chronic Kidney Disease

Yun

Lee

2019

IJMS

View full text Add to dashboard Cite

Kidney disease can be either acute kidney injury (AKI) or chronic kidney disease (CKD) and it can lead to the development of functional organ failure. Mesenchymal stem cells (MSCs) are derived from a diverse range of human tissues. They are multipotent and have immunomodulatory effects to assist in the recovery from tissue injury and the inhibition of inflammation. Numerous studies have investigated the feasibility, safety, and efficacy of MSC-based therapies for kidney disease. Although the exact mechanism of MSC-based therapy remains uncertain, their therapeutic value in the treatment of a diverse range of kidney diseases has been studied in clinical trials. The use of MSCs is a promising therapeutic strategy for both acute and chronic kidney disease. The mechanism underlying the effects of MSCs on survival rate after transplantation and functional repair of damaged tissue is still ambiguous. The paracrine effects of MSCs on renal recovery, optimization of the microenvironment for cell survival, and control of inflammatory responses are thought to be related to their interaction with the damaged kidney environment. This review discusses recent experimental and clinical findings related to kidney disease, with a focus on the role of MSCs in kidney disease recovery, differentiation, and microenvironment. The therapeutic efficacy and current applications of MSC-based kidney disease therapies are also discussed.

show abstract

Section: Msc-based Therapy For Kidney Diseasementioning

confidence: 99%

Potential and Therapeutic Efficacy of Cell-based Therapy Using Mesenchymal Stem Cells for Acute/chronic Kidney Disease

Yun

Lee

2019

IJMS

View full text Add to dashboard Cite

show abstract

“…By reducing renal expression of NF-κB, TNF-α, IFN-γ, MCP-1, and oxidative stress, MSC restores kidney function in atherosclerotic renal artery stenosis-induced AKI in pigs [ 127 ]. The main obstacles that must be addressed with MSC are the safety, dose, source of cells, and delivery methods [ 187 , 204 ]. To circumvent some of these obstacles, Lerman and colleagues have shown that intrarenal delivery of MSC extracellular vesicles achieves similar results as MSC in the attenuation of AKI in pigs [ 128–130 ].…”

Section: Mechanistic Strategies Of Aki For Evaluating Therapeutics Inmentioning

confidence: 99%

“…Therefore, an intervention might not be equally effective in different species of LAM. For example, MSC therapy is reported to be effective in dogs and pigs [ 187 ] but not in cats [ 183 ] or sheep [ 179 ]. Even among the same species, the same treatment can have different results in different AKI models.…”

Section: Limitations Of Lam In Aki Studiesmentioning

confidence: 99%

Large animal models for translational research in acute kidney injury

et al. 2020

View full text Add to dashboard Cite

While extensive research using animal models has improved the understanding of acute kidney injury (AKI), this knowledge has not been translated into effective treatments. Many promising interventions for AKI identified in mice and rats have not been validated in subsequent clinical trials. As a result, the mortality rate of AKI patients remains high. Inflammation plays a fundamental role in the pathogenesis of AKI, and one reason for the failure to translate promising therapeutics may lie in the profound difference between the immune systems of rodents and humans. The immune systems of large animals such as swine, nonhuman primates, sheep, dogs and cats, more closely resemble the human immune system. Therefore, in the absence of a basic understanding of the pathophysiology of human AKI, large animals are attractive models to test novel interventions. However, there is a lack of reviews on large animal models for AKI in the literature. In this review, we will first highlight differences in innate and adaptive immunities among rodents, large animals, and humans in relation to AKI. After illustrating the potential merits of large animals in testing therapies for AKI, we will summarize the current state of the evidence in terms of what therapeutics have been tested in large animal models. The aim of this review is not to suggest that murine models are not valid to study AKI. Instead, our objective is to demonstrate that large animal models can serve as valuable and complementary tools in translating potential therapeutics into clinical practice.

show abstract

“…Recently, accumulating evidence has suggested that transplantation of mesenchymal stem cells (MSCs) may be a potentially effective therapy for cisplatin-induced AKI (8–10). MSCs are self-renewable multipotent progenitor cells with the potential to transdifferentiate into a variety of cell types under certain conditions, including renal proximal tubule epithelial cells (11).…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, MSCs have immunomodulatory characteristics that promote the induction of anti-inflammatory regulatory T (Treg) cells (12), but inhibit the influx of pro-inflammatory leukocytes, macrophages, dendritic cells (DCs), neutrophils, CD4 + T helper (Th), and CD8 + cytotoxic T lymphocytes (CTLs) (8), leading to production of less inflammatory cytokines that cause renal cell apoptosis (12,13). Despite evidence for the therapeutic potential of MSCs (10), the clinical use of MSCs remains limited because the molecular mechanisms remain not well understood and the cost is high. Therefore, further investigation of the mechanisms of MSC therapy for AKI and exploration of drugs with similar function to MSCs are of the essence.…”

Section: Introductionmentioning

confidence: 99%

miRNA‑mRNA regulatory network analysis of mesenchymal stem cell treatment in cisplatin‑induced acute kidney injury identifies roles for miR‑210/Serpine1 and miR‑378/Fos in regulating inflammation

Zhang

Zhao

et al. 2019

Mol Med Report

View full text Add to dashboard Cite

The present study aimed to identify microRNAs (miRNAs) that may be crucial for the mechanism of mesenchymal stem cell (MSC) treatment in cisplatin-induced acute kidney injury (AKI) and to investigate other potential drugs that may have a similar function. Transcriptomics (GSE85957) and miRNA expression (GSE66761) datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified using the linear models for microarray data method and mRNA targets of DEMs were predicted using the miRWalk2.0 database. The crucial DEGs were screened by constructing a protein-protein interaction (PPI) network and module analysis. Functions of target genes were analyzed using the database for annotation, visualization and integrated discovery. Small molecule drugs were predicted using the connectivity map database. As a result, 5 DEMs were identified to be shared and oppositely expressed in comparisons between AKI model and control groups, and between MSC treatment and AKI model groups. The 103 DEGs were overlapped with the target genes of 5 common DEMs, and the resulting list was used for constructing the miRNA-mRNA regulatory network, including rno-miR-210/Serpine1 and rno-miR-378/Fos. Serpine1 (degree=17) and Fos (degree=42) were predicted to be hub genes according to the topological characteristic of degree in the PPI network. Function analysis indicated Serpine1 and Fos may be inflammation-related. Furthermore, gliclazide was suggested to be a potential drug for the treatment of AKI because the enrichment score was the closest to −1 (−0.9). In conclusion, it can be speculated that gliclazide may have a similar mechanism to MSC as a potential therapeutic agent for cisplatin-induced AKI, by regulating miR-210/Serpine1 and miR-378-/Fos-mediated inflammation and cell apoptosis.

show abstract

Mesenchymal Stem Cells Contribute to Improvement of Renal Function in a Canine Kidney Injury Model

Abstract: Abstract. Background

Cited by 20 publications

References 38 publications

Potential and Therapeutic Efficacy of Cell-based Therapy Using Mesenchymal Stem Cells for Acute/chronic Kidney Disease

Potential and Therapeutic Efficacy of Cell-based Therapy Using Mesenchymal Stem Cells for Acute/chronic Kidney Disease

Large animal models for translational research in acute kidney injury

miRNA‑mRNA regulatory network analysis of mesenchymal stem cell treatment in cisplatin‑induced acute kidney injury identifies roles for miR‑210/Serpine1 and miR‑378/Fos in regulating inflammation

Contact Info

Product

Resources

About