(Mesenchymal) Stem Cell-Based Therapy in Cisplatin-Induced Acute Kidney Injury Animal Model: Risk of Immunogenicity and Tumorigenicity

Večerić-Haler, Željka; Cerar, Anton; Perše, Martina

doi:10.1155/2017/7304643

Cited by 45 publications

(32 citation statements)

References 80 publications

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“…In spite of the trophic effects of MSC-EVs in the point of immunomodulation, MSC-EVs treatment potentially mediates negative immunomodulatory effects [113]. For example, Kilpinen et al analyzed the secretomes of umbilical-cord-derived MSC-EVs with or without the interferon-gamma (IFN-γ) stimulus and indicated that EVs from MSCs treated with IFN-γ for 24 h contained major histocompatibility Class I (MHCI) and both α and β units of the proteasome complex required for the antigen presentation and activation of T cells [114].…”

Section: Immunomodulatory Effect Of Evs From Mscs Against Renal Injurymentioning

confidence: 99%

Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Renal Diseases

Tsuji

Kitamura

Wada

2020

IJMS

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Mesenchymal stem cells (MSCs) have immunomodulatory and regenerative effects in many organs, including the kidney. Emerging evidence has shown that the trophic effects from MSCs are mainly mediated by the paracrine mechanism rather than the direct differentiation of MSCs into injured tissues. These secretomes from MSCs include cytokines, growth factors, chemokines and extracellular vesicles (EVs) containing microRNAs, mRNAs, and proteins. Many research studies have revealed that secretomes from MSCs have potential to ameliorate renal injury in renal disease models, including acute kidney injury and chronic kidney disease through a variety of mechanisms. These trophic mechanisms include immunomodulatory and regenerative effects. In addition, accumulating evidence has uncovered the specific factors and therapeutic mechanisms in MSC-derived EVs. In this article, we summarize the recent advances of immunomodulatory and regenerative effects of EVs from MSCs, especially focusing on the microRNAs.

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Section: Immunomodulatory Effect Of Evs From Mscs Against Renal Injurymentioning

confidence: 99%

Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Renal Diseases

Tsuji

Kitamura

Wada

2020

IJMS

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“…To help understand complex mechanisms involved in the development of kidney injury cisplatin rodent model has been developed and extensively used to investigate cisplatin metabolism and the molecular mechanisms of cisplatin nephrotoxicity [ 3 , 4 ] and to test new generations of platinum-based chemotherapy drugs or adjunctive therapies [ 5 , 6 ] or other potential agents [ 7 ] or strategies to prevent or treat AKI (for instance, stem cells) [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges

Perše

Večerić-Haler

2018

BioMed Research International

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Cisplatin is an antitumor drug used in the treatment of a wide variety of malignancies. However, its primary dose-limiting side effect is kidney injury, which is a major clinical concern. To help understand mechanisms involved in the development of kidney injury, cisplatin rodent model has been developed. Given the complex pathogenesis of kidney injury, which involves both local events in the kidney and interconnected and interdependent systemic effects in the body, cisplatin rodent model is indispensable in the investigation of underlying mechanisms and potential treatment strategies of both acute and chronic kidney injury. Cisplatin rodent model is well appreciated and widely used model due to its simplicity. It has many similarities to human cisplatin nephrotoxicity, which are mentioned in the paper. In spite of its simplicity and wide applicability, there are also traps that need to be taken into account when using cisplatin model. The present paper is aimed at giving a concise insight into the complex characteristics of cisplatin rodent model and heterogeneity of cisplatin dosage regimens as well as outlining factors that can severely influence the outcome of the model and the study. Challenges for future research are also mentioned.

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“…Adult and fetal bone marrow-derived mesenchymal stem cells (BM-MSCs) have been shown to be capable of repairing renal function deficits [ 19 , 20 ]. BM-MSCs have potent immunosuppressive properties and their potential application in acute kidney injury animal models has been studied recently [ 21 ]. However, the use of adult BM-MSCs has some limitations such as the low number of MSCs in adult bone marrow, expression of ageing-associated factors, slow expansion rate, early senescence, inactive telomerase, shorter telomeres and restricted differentiation potential [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

The presence of human mesenchymal stem cells of renal origin in amniotic fluid increases with gestational time

et al. 2018

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BackgroundEstablished therapies for managing kidney dysfunction such as kidney dialysis and transplantation are limited due to the shortage of compatible donated organs and high costs. Stem cell-based therapies are currently under investigation as an alternative treatment option. As amniotic fluid is composed of fetal urine harboring mesenchymal stem cells (AF-MSCs), we hypothesized that third-trimester amniotic fluid could be a novel source of renal progenitor and differentiated cells.MethodsHuman third-trimester amniotic fluid cells (AFCs) were isolated and cultured in distinct media. These cells were characterized as renal progenitor cells with respect to cell morphology, cell surface marker expression, transcriptome and differentiation into chondrocytes, osteoblasts and adipocytes. To test for renal function, a comparative albumin endocytosis assay was performed using AF-MSCs and commercially available renal cells derived from kidney biopsies. Comparative transcriptome analyses of first, second and third trimester-derived AF-MSCs were conducted to monitor expression of renal-related genes.ResultsRegardless of the media used, AFCs showed expression of pluripotency-associated markers such as SSEA4, TRA-1-60, TRA-1-81 and C-Kit. They also express the mesenchymal marker Vimentin. Immunophenotyping confirmed that third-trimester AFCs are bona fide MSCs. AF-MSCs expressed the master renal progenitor markers SIX2 and CITED1, in addition to typical renal proteins such as PODXL, LHX1, BRN1 and PAX8. Albumin endocytosis assays demonstrated the functionality of AF-MSCs as renal cells. Additionally, upregulated expression of BMP7 and downregulation of WT1, CD133, SIX2 and C-Kit were observed upon activation of WNT signaling by treatment with the GSK-3 inhibitor CHIR99201. Transcriptome analysis and semiquantitative PCR revealed increasing expression levels of renal-specific genes (e.g., SALL1, HNF4B, SIX2) with gestational time. Moreover, AF-MSCs shared more genes with human kidney cells than with native MSCs and gene ontology terms revealed involvement of biological processes associated with kidney morphogenesis.ConclusionsThird-trimester amniotic fluid contains AF-MSCs of renal origin and this novel source of kidney progenitors may have enormous future potentials for disease modeling, renal repair and drug screening.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0864-7) contains supplementary material, which is available to authorized users.

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(Mesenchymal) Stem Cell-Based Therapy in Cisplatin-Induced Acute Kidney Injury Animal Model: Risk of Immunogenicity and Tumorigenicity

Cited by 45 publications

References 80 publications

Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Renal Diseases

Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Renal Diseases

Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges

The presence of human mesenchymal stem cells of renal origin in amniotic fluid increases with gestational time

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