Preconditioning strategies for improving the survival rate and paracrine ability of mesenchymal stem cells in acute kidney injury

Zhao, Lingfei; Hu, Chenxia; Zhang, Ping; Jiang, Hua; Chen, Jianghua

doi:10.1111/jcmm.14035

Cited by 58 publications

(44 citation statements)

References 108 publications

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“…Various modi cations of MSCs have been attempted to improve their survival rates and therapeutic e cacy [31,32,34,35]. Attempts to improve stem cell survival, metabolism, or migration ability have focused on genetic modi cations to knock-out or knock-in speci c genes [36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects

Park

Kim²,

Kwon³

et al. 2020

Preprint

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BackgroundMesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of Alzheimer’s disease (AD). Previous studies suggested that the co-culture of human MSCs with AD in an in vitro model reduced the expression of amyloid-beta 42 (Aβ42) in the medium as well as the overexpression of amyloid-beta (Aβ )-degrading enzymes such as neprilysin (NEP).MethodsIn this study, we focused on the role of primed MSCs (human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exposed to an AD cell line via a co-culture system) in reducing the levels of Aβ and inhibiting cell death. ResultsWe demonstrated that mouse groups treated with naïve MSCs and primed MSCs showed significant reductions in cell death, ubiquitin conjugate levels, and Aβ levels, but the effects were greater in primed MSCs. Also, mRNA sequencing data analysis indicated that high levels of TGF-β induced primed-MSCs. Furthermore, treatment with TGF-β reduced Aβ expression in an AD transgenic mouse model. ConclusionAD environmental preconditioning is a promising strategy to reduce cell death and ubiquitin conjugate levels and maintain the stemness of MSCs. Further, these data suggest that human WJ-MSCs exposed to an AD environment may represent a promising and novel therapy for AD.

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Section: Discussionmentioning

confidence: 99%

Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects

Park

Kim²,

Kwon³

et al. 2020

Preprint

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“…Cell-free treatments including the microvesicles, exosomes, specific cytokines, miRNA, and the pretreatment of MSCs represent viable alternatives to address the issue of long-term negative effects [25][26][27]. Application of pretreated-MSCs is a novel strategy to enhance the capacity of MSCs to migrate and promote tissue repair in the treatment of kidney injury [28]. Pretreatment with cytokines such as transforming growth factor β1 (TGF-β1), interleukin-17A (IL-17A), and melatonin before infusion can increase the number of MSCs that home to the injured kidney, promote the recovery of renal function, and ameliorate impairments to the renal structure [3,17,29].…”

Section: Discussionmentioning

confidence: 99%

Bone mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury

Zhou

Qiao

Liu

et al. 2020

Preprint

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Background Mesenchymal stem cells (MSCs) represent a promising treatment option for acute kidney injury (AKI).The main drawbacks of MSC therapy including the lack of specific homing following systemic infusion and early death of the cells in the inflammatory microenvironment, directly affect the therapeutic efficacy of MSCs. Erythropoietin (EPO)-preconditioning promotes the therapeutic effect of the MSCs, although the underlying mechanism remains unknown. In this study, we sought to investigate the efficacy and mechanism of EPO on bone marrow mesenchymal stem cells (BMSCs) for the treatment of AKI. ResultsWe found that incubation of BMSCs with ischemia/reperfusion(I/R)-induced AKI kidney homogenate supernatant (KHS) caused apoptosis in the BMSCs, which was decreased following EPO pretreatment indicating that EPO protected the cells from apoptosis. Further, we found that EPO upregulated SIRT1 and Bcl-2 expression, and downregulated p53 expression. The EPO-mediated antiapoptotic mechanism in pretreated BMSCs may be mediated though the SIRT1 pathway. In a rat AKI model, our data showed that 24 h following intravenous infusion, GFP-BMSCs were predominantly in the lungs. However, EPO pretreatment reduced the lung entrapment of BMSCs, and increased the distribution of the BMSCs to the target organs. AKI rats infused with EPO-BMSCs had significantly lower levels of serum IL-1β and TNF-a and significantly higher level of IL-10 compared to rats infused with BMSCs. The administration of EPO-BMSCs after reperfusion was more effective in reducing serum creatinine, blood urea nitrogen, and pathological scores in the I/R-AKI rats than BMSCs.Conclusions Our data suggest that EPO pretreatment enhances the efficacy of BMSCs in improving renal function and pathological presentation in I/R-AKI rats. BackgroundAcute kidney injury (AKI) is one of the most clinically impactful diseases with high morbidity and mortality [1,2]. Multiple injuries such as those resulting from sepsis, ischemia/reperfusion (I/R), and drug administration may induce AKI. I/R injury is a major cause of human AKI, which is associated with tubular necrosis, cast formation, tubular dilation, loss of brush border, and inflammation [3]. AKI remains a worldwide public health concern due to the increased risk for subsequent development of 4 chronic kidney disease (CKD) [4]. The annual medical expenses associated with AKI treatment places a heavy burden on the public health care system, and yet AKI lacks an established treatment strategy. Therefore, there is an urgent need to find innovative and effective therapeutic strategies for AKI. The application of mesenchymal stem cells (MSCs) has been suggested as a potentially promising treatment strategy for AKI [5,6].In the recent years, MSCs have become an area of intense research in the field of stem cell therapy.MSCs are adherent, fibroblast-like cells, derived from different tissues and organs including bone marrow, umbilical cord blood, adipose tissue, and solid organs that have the potential for multidirectional diff...

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“…Cell-free treatments, including microvesicles, exosomes, speci c cytokines, miRNA, and the pretreatment of MSCs, represent viable alternatives to address the issue of long-term negative effects [21][22][23]. Pretreating MSCs is a novel strategy to enhance the capacity of MSCs to migrate and promote tissue repair in injured kidneys [24]. Pretreatment, before infusion, with cytokines such as transforming growth factor β1 (TGF-β1), interleukin-17A (IL-17A), and melatonin can increase the number of MSCs homing to the injured kidney, promote the recovery of renal function, and ameliorate renal impairments [3,17,25].…”

Section: Discussionmentioning

confidence: 99%

Bone marrow derived mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury

Zhou

Qiao

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Mesenchymal stem cells (MSCs) represent a promising treatment option for acute kidney injury (AKI). The main drawbacks of MSCs therapy, including the lack of specific homing after systemic infusion and early cell death in the inflammatory microenvironment, directly affect the therapeutic efficacy of MSCs. Erythropoietin (EPO)-preconditioning of MSCs promotes their therapeutic effect; however, the underlying mechanism remains unknown. In this study, we sought to investigate the efficacy and mechanism of EPO in bone marrow derived mesenchymal stem cells (BMSCs) for AKI treatment. Results We found that incubation of BMSCs with ischemia/reperfusion(I/R)-induced AKI kidney homogenate supernatant (KHS) caused apoptosis in BMSCs, which was decreased by EPO pretreatment, indicating that EPO protected the cells from apoptosis. Further, we showed that EPO up-regulated SIRT1 and Bcl-2 expression and down-regulated p53 expression. This effect was partially reversed by SIRT1 siRNA intervention. The anti-apoptotic effect of EPO in pretreated BMSCs may be mediated through the SIRT1 pathway. In a rat AKI model, 24 h after intravenous infusion, GFP-BMSCs were predominantly located in the lungs. However, EPO pretreatment reduced the lung entrapment of BMSCs and increased their distribution in the target organs. AKI rats infused with EPO-BMSCs had significantly lower levels of serum IL-1β and TNF-α, and a significantly higher level of IL-10 as compared to rats infused with untreated BMSCs. The administration of EPO-BMSCs after reperfusion reduced serum creatinine, blood urea nitrogen, and pathological scores in I/R-AKI rats more effectively than BMSCs treatment did. Conclusions Our data suggest that EPO pretreatment enhances the efficacy of BMSCs to improve the renal function and pathological presentation of I/R-AKI rats.

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Preconditioning strategies for improving the survival rate and paracrine ability of mesenchymal stem cells in acute kidney injury

Cited by 58 publications

References 108 publications

Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects

Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects

Bone mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury

Bone marrow derived mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury

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