Mesenchymal stem cells, not conditioned medium, contribute to kidney repair after ischemia-reperfusion injury

Li, Xing; Cui, Rui; Peng, Lei; Ma, Jing; Chen, Xiao; Xie, Ruiqin; Li, Bing

doi:10.1186/scrt489

Cited by 74 publications

(73 citation statements)

References 46 publications

(46 reference statements)

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“…In addition, significant increase in thickness of tubular basement membrane as compared with control group and significant decrease in PCNA immuno-reactivity as compared to stem cell-treated group was detected. Similar results were recorded by previous investigators [13] , who stated that even after administration of high consecutive doses of CM, no improvement had been observed in animal models of ischemia reperfusion kidney injury. On the contrary, other researchers reported that CM improved renal function and increased survival in AKI experimental models [37] .…”

Section: Discussionsupporting

confidence: 80%

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Role of Mesenchymal Stem Cells Versus their Conditioned Medium on Cisplatin-Induced Acute Kidney Injury in Albino Rat. A Histological and Immunohistochemical Study

Zaher

Shawarby

Hammouda

et al. 2017

Egyptian Journal of Histology

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Introduction: Acute kidney injury (AKI) is a syndrome of rapidly declining renal function. Cisplatin nephrotoxicity is a major cause of AKI in about one third of patients under cisplatin treatment. Stem cell therapy have been suggested as a protective measure against cisplatin-induced AKI. The conditioned medium of the stem cells (serum-free culture medium) has been also found to minimize renal injury and might develop a new therapeutic strategy that avoids stem cells administration. Aim of the Study:This study was conducted to compare the effect of intravenous injection of bone marrow-derived mesenchymal stem cells (BMSCs) versus their conditioned medium (CM) in minimizing the cisplatin-induced acute renal injury. Material and Methods: Sixty adult female albino rats were divided into 4 main groups. Group (I) served as a control group, Group (II) (cisplatin treated group) that were subdivided into two subgroups IIa and IIb, Group (III) (BMSCstreated group) and Group (IV) (CM-treated group). Five young male rats were additionally used for obtaining the BMSCs. Rats of all groups were sacrificed on 4th day of the experiment, except for the rats of subgroup (IIa (which were sacrificed after one day of cisplatin administration. Renal specimens were prepared for histological and immunohistochemical techniques. Morphometrical studies and statistical analysis were performed. Results: Treatment by BMSCs resulted in obvious improvement of renal structure with significant increase in Proliferating Cell Nuclear Antigen (PCNA). However, conditioned medium (CM) was less effective in treatment of acute AKI. Conclusion: BMSCs administration is preferable than their CM in reversing the acute structural damage of the kidney induced by cisplatin.

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Section: Discussionsupporting

confidence: 80%

“…One day after cisplatin injection, the BMSCs suspension was injected into the rat tail vein, in a dose of 2 x106 in 0.5 ml PBS/rat [13] . Rats of this group were sacrificed three days after cisplatin injection (4 th day of the experiment).…”

mentioning

confidence: 99%

Role of Mesenchymal Stem Cells Versus their Conditioned Medium on Cisplatin-Induced Acute Kidney Injury in Albino Rat. A Histological and Immunohistochemical Study

Zaher

Shawarby

Hammouda

et al. 2017

Egyptian Journal of Histology

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“…The conditioned medium of OSR1 + SIX2 + cells was generated as previously reported [24]. In brief, 1 3 10 5 OSR1…”

Section: Graft Preparation and Implantationmentioning

confidence: 99%

Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury in Mice

Toyohara

Mae

Sueta

et al. 2015

Stem Cells Translational Medicine

137

138

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Acute kidney injury (AKI) is defined as a rapid loss of renal function resulting from various etiologies, with a mortality rate exceeding 60% among intensive care patients. Because conventional treatments have failed to alleviate this condition, the development of regenerative therapies using human induced pluripotent stem cells (hiPSCs) presents a promising new therapeutic option for AKI. We describe our methodology for generating renal progenitors from hiPSCs that show potential in ameliorating AKI. We established a multistep differentiation protocol for inducing hiPSCs into OSR1 + SIX2 + renal progenitors capable of reconstituting three-dimensional proximal renal tubule-like structures in vitro and in vivo. Moreover, we found that renal subcapsular transplantation of hiPSC-derived renal progenitors ameliorated the AKI in mice induced by ischemia/reperfusion injury, significantly suppressing the elevation of blood urea nitrogen and serum creatinine levels and attenuating histopathological changes, such as tubular necrosis, tubule dilatation with casts, and interstitial fibrosis. To our knowledge, few reports demonstrating the therapeutic efficacy of cell therapy with renal lineage cells generated from hiPSCs have been published. Our results suggest that regenerative medicine strategies for kidney diseases could be developed using hiPSC-derived renal cells. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:980-992 SIGNIFICANCEThis report is the first to demonstrate that the transplantation of renal progenitor cells differentiated from human induced pluripotent stem (iPS) cells has therapeutic effectiveness in mouse models of acute kidney injury induced by ischemia/reperfusion injury. In addition, this report clearly demonstrates that the therapeutic benefits come from trophic effects by the renal progenitor cells, and it identifies the renoprotective factors secreted by the progenitors. The results of this study indicate the feasibility of developing regenerative medicine strategy using iPS cells against renal diseases.

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“…In previous studies, MSC-conditioned medium and MSCs released by extracellular vesicles (Evs) were reported to exert renoprotective effects against AKI (9)(10)(11). The researchers attributed these effects to the favorable molecules, such as mRNA and miRNA (11) indicated that CM may not be able to protect against kidney injury (12,13). EVs, such as exosomes and shedding vesicles (also known as microvesicles; Mvs) are membranous structures that deliver bioactive molecular content, including proteins, mRNA and micro (mi)RNA sequences (14).…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles derived from mesenchymal stromal cells may possess increased therapeutic potential for acute kidney injury compared with conditioned medium in rodent models: A meta-analysis

Zhang

Wang

Miao

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The potential involvement of the endocrine/paracrine mechanisms in the mesenchymal stromal cells (MSCs) therapy for acute kidney injury (AKI) has been increasingly studied. The aim of the present meta-analysis was to systematically review the therapeutic role of MSC-conditioned medium (CM) or MSCs released by extracellular vesicles (Evs) for the treatment of AKI in rodent models. Studies were identified using PubMed and Scopus databases using a custom search strategy and eligibility criteria. Data regarding serum creatinine (SCr) concentration, CM or Evs, measurement time point, AKI model (toxic or non-toxic) and other parameters, including delivery route, animal type and animal numbers, were extracted. Pooled analysis and subgroup analysis as well as multivariable meta-regression were performed. Heterogeneity and publication bias were also investigated. A total of 13 studies were included and analyzed. Pooled analysis showed reduced SCr (0.93 [0.67, 1.20], mg/dl) in rodent models of AKI after CM/Evs therapy. The results of the subgroup analysis suggested that Evs induced an increased therapeutic effect, in the form of SCr reduction, as compared with CM (P= 0.05). There were also other significant influential factors for SCr reduction including measurement time point (P=0.0004) and therapeutic time point (P<0.0001) after surgery. By contrast, parameters such as delivery route, injury type and cell type were not significant influential factors.Multivariable meta-regression analysis showed that measurement time point (P=0.041), therapeutic time point (P=0.03), Evs or CM (P=0.0003) and cell type (P<0.0001) were influential factors in the reduction of SCr. The present meta-analysis indicates that CM or Evs derived from MSCs are able to improve the impaired renal function in rodents modelling AKI. Compared with CM, Evs may produce a more marked therapeutic effect in recovery from renal failure. In addition, CM or Evs administration in early stages of AKI may result in more evident effects. IntroductionAcute kidney injury (AKI) refers to a clinical syndrome characterized by a rapid (hours to days) reduction in renal excretory function, with the accumulation of creatinine and urea nitrogen and other waste products that are not commonly tested in clinical practice (1). AKI is commonly observed in clinical practice, particularly following major surgery and treatment in intensive care units (2). In addition, AKI mortality is high, ranging between 24 and 62% (3). Patients that survive AKI may have an increased long-term risk of developing chronic kidney disease with poor prognosis (4). There is therefore an urgent requirement for novel methods for the prevention and management of AKI.In recent years, a promising and effective therapeutic strategy for AKI involves the use of mesenchymal stromal cells (MSCs) derived from various sources, such as bone marrow or adipose (5,6). However, the mechanisms are not understood well. It has been suggested that MSCs promote renal injury repair, predominantly via paracrine/e...

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Mesenchymal stem cells, not conditioned medium, contribute to kidney repair after ischemia-reperfusion injury

Cited by 74 publications

References 46 publications

Role of Mesenchymal Stem Cells Versus their Conditioned Medium on Cisplatin-Induced Acute Kidney Injury in Albino Rat. A Histological and Immunohistochemical Study

Role of Mesenchymal Stem Cells Versus their Conditioned Medium on Cisplatin-Induced Acute Kidney Injury in Albino Rat. A Histological and Immunohistochemical Study

Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury in Mice

Extracellular vesicles derived from mesenchymal stromal cells may possess increased therapeutic potential for acute kidney injury compared with conditioned medium in rodent models: A meta-analysis

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