Adipose‐derived mesenchymal stem cells therapy for acute kidney injury induced by ischemia‐reperfusion in a rat model

Zhang, Jianbo; Wang, Xiaoqiao; Lu, Guolin; Huang, Huansen; Xu, Shiyuan

doi:10.1111/1440-1681.12811

Cited by 26 publications

(25 citation statements)

References 42 publications

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“…In recent years, stem cell therapy has drawn much attention for the treatment of AKI [ 7 ]. As a main player, MSCs derived from different sources like adipose, bone-marrow and human umbilical cord have shown renoprotective effects in several models of toxin or IRI-induced AKI [ 31 – 33 ]. Meanwhile, numerous controversies have arisen regarding safety, cost, availability, and ethical considerations of MSCs [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury

et al. 2020

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Background Acute kidney injury (AKI) is a common clinical disease with complex pathophysiology and limited therapeutic choices. This prompts the need for novel therapy targeting multiple aspects of this disease. Human amnion epithelial cell (hAEC) is an ideal stem cell source. Increasing evidence suggests that exosomes may act as critical cell–cell communicators. Accordingly, we assessed the therapeutic potential of hAECs and their derived exosomes (hAECs-EXO) in ischemia reperfusion mouse model of AKI and explored the underlying mechanisms. Methods The hAECs were primary cultured, and hAECs-EXO were isolated and characterized. An ischemic-reperfusion injury-induced AKI (IRI-AKI) mouse model was established to mimic clinical ischemic kidney injury with different disease severity. Mouse blood creatinine level was used to assess renal function, and kidney specimens were processed to detect cell proliferation, apoptosis, and capillary density. Macrophage infiltration was analyzed by flow cytometry. hAEC-derived exosomes (hAECs-EXO) were used to treat hypoxia-reoxygenation (H/R) injured HK-2 cells and mouse bone marrow-derived macrophages to evaluate their protective effect in vitro. Furthermore, hAECs-EXO were subjected to liquid chromatography-tandem mass spectrometry for proteomic profiling. Results We found that systematically administered hAECs could improve mortality and renal function in IRI-AKI mice, decrease the number of apoptotic cells, prevent peritubular capillary loss, and modulate kidney local immune response. However, hAECs showed very low kidney tissue integration. Exosomes isolated from hAECs recapitulated the renal protective effects of their source cells. In vitro, hAECs-EXO protected HK-2 cells from H/R injury-induced apoptosis and promoted bone marrow-derived macrophage polarization toward M2 phenotype. Proteomic analysis on hAECs-EXO revealed proteins involved in extracellular matrix organization, growth factor signaling pathways, cytokine production, and immunomodulation. These findings demonstrated that paracrine of exosomes might be the key mechanism of hAECs in alleviating renal ischemia reperfusion injury. Conclusions We reported hAECs could improve survival and ameliorate renal injury in mice with IRI-AKI. The anti-apoptotic, pro-angiogenetic, and immunomodulatory capabilities of hAECs are at least partially, through paracrine pathways. hAECs-EXO might be a promising clinical therapeutic tool, overcoming the weaknesses and risks associated with the use of native stem cells, for patients with AKI.

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Section: Discussionmentioning

confidence: 99%

Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury

et al. 2020

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“…To evaluate the efficacy and possible benefits from stem cells application in the management of ischemic injuries, the state of acute ischemia has been provoked in experimental animal models. It was observed that the administration of ASCs could protect tissues against the consequences of acute ischemic injury and modulate their reorganization after myocardial infarction, ischemic stroke, or acute renal ischemic injury [82][83][84][85][86][87][88][89]. Nevertheless, it is worth mentioning that the results of a randomized clinical trial did not support the thesis that the injection of ASCs could minimize kidney injury and could improve renal function after the induced acute ischemia [90].…”

Section: Animal Modelsmentioning

confidence: 99%

In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications

Jankowski

Dompe

Sibiak

et al. 2020

Cells

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Adipose-derived stem cells (ASCs) exhibiting mesenchymal stem cell (MSC) characteristics, have been extensively studied in recent years. Because they have been shown to differentiate into lineages such as osteogenic, chondrogenic, neurogenic or myogenic, the focus of most of the current research concerns either their potential to replace bone marrow as a readily available and abundant source of MSCs, or to employ them in regenerative and reconstructive medicine. There is close to consensus regarding the methodology used for ASC isolation and culture, whereas a number of molecular analyses implicates them in potential therapies of a number of pathologies. When it comes to clinical application, there is a range of examples of animal trials and clinical studies employing ASCs, further emphasizing the advancement of studies leading to their more widespread use. Nevertheless, in vitro studies will most likely continue to play a significant role in ASC studies, both providing the molecular knowledge of their ex vivo properties and possibly serving as an important step in purification and application of those cells in a clinical setting. Therefore, it is important to consider current methods of ASC isolation, culture, and processing. Furthermore, molecular analyses and cell surface properties of ASCs are essential for animal studies, clinical studies, and therapeutic applications of the MSC properties.

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“…Another very important pathophysiological mechanism involved in AKI I/R is the so-called sterile inflammation. In this regard, ASC have shown to downregulate the expression of inflammatory cytokines and chemokines (IL-6, TNF-α, IL-1β, IFN⋎, CXCL2) and upregulate the anti-inflammatory cytokine IL-10 ( 233 , 234 ). Macrophage number and migration was reduced in a study using iPSC and hWJ-MSC-EVs where the effect was observed in terms of downregulation of MCP-1 and CX3CL1 (chemoattractant factor for macrophages) ( 160 , 235 ).…”

Section: Msc Therapy In the Treatment Of Kidney Diseases: State Of Thmentioning

confidence: 99%

Stem/Stromal Cells for Treatment of Kidney Injuries With Focus on Preclinical Models

et al. 2018

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Within the last years, the use of stem cells (embryonic, induced pluripotent stem cells, or hematopoietic stem cells), Progenitor cells (e.g., endothelial progenitor cells), and most intensely mesenchymal stromal cells (MSC) has emerged as a promising cell-based therapy for several diseases including nephropathy. For patients with end-stage renal disease (ESRD), dialysis or finally organ transplantation are the only therapeutic modalities available. Since ESRD is associated with a high healthcare expenditure, MSC therapy represents an innovative approach. In a variety of preclinical and clinical studies, MSC have shown to exert renoprotective properties, mediated mainly by paracrine effects, immunomodulation, regulation of inflammation, secretion of several trophic factors, and possibly differentiation to renal precursors. However, studies are highly diverse; thus, knowledge is still limited regarding the exact mode of action, source of MSC in comparison to other stem cell types, administration route and dose, tracking of cells and documentation of therapeutic efficacy by new imaging techniques and tissue visualization. The aim of this review is to provide a summary of published studies of stem cell therapy in acute and chronic kidney injury, diabetic nephropathy, polycystic kidney disease, and kidney transplantation. Preclinical studies with allogeneic or xenogeneic cell therapy were first addressed, followed by a summary of clinical trials carried out with autologous or allogeneic hMSC. Studies were analyzed with respect to source of cell type, mechanism of action etc.

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Adipose‐derived mesenchymal stem cells therapy for acute kidney injury induced by ischemia‐reperfusion in a rat model

Cited by 26 publications

References 42 publications

Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury

Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury

In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications

Stem/Stromal Cells for Treatment of Kidney Injuries With Focus on Preclinical Models

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