Protective effects of mesenchymal stromal cells on adriamycin-induced minimal change nephrotic syndrome in rats and possible mechanisms

Guo, Junqi; Zou, Yuhua; Wu, Zhixian; Wu, Wenjun; Xu, Zizhong; Hu, Heyi; Huang, Lianghu; Dong, Huiyue; Chen, Jin; Lü, Jun; Fu, Yan; Wang, Jin; Ma, Yujie; Chen, Xiaowen; He, Fuqiang; Yang, Shaodong; Liao, Lianming; Chen, Jian; Zhao, Feng; Tan, Ming Jen

doi:10.1016/j.jcyt.2013.08.002

Cited by 15 publications

(12 citation statements)

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“…Adriamycin-induced nephropathy in mice is reported to be an excellent model commonly used for pharmacological intervention studies by virtue of its capability to recapitulate the cardinal features of kidney disease including biochemical changes in serum and urine, morphologic features of glomerulosclerosis, and clinical nephrosis [ 26 ]. It is also a prevailing model to test the efficacy of stem cells on kidney disease in the past decade [ 27 – 29 ]. To circumvent the issue of immunorejection of exogenous human cells in mice, we chose to establish AN in NOD/SCID mice.…”

Section: Discussionmentioning

confidence: 99%

Human induced pluripotent stem cell-derived mesenchymal stem cells prevent adriamycin nephropathy in mice

Yiu

Wong

et al. 2017

Oncotarget

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Human induced pluripotent stem cell-derived mesenchymal stem cells (iPS-MSCs) are emerging as attractive options for use in cell replacement therapy, but their effect in kidney diseases remains unknown. Here, we showed that intravenous injection of iPS-MSCs protect against renal function loss in both short-term and long-term models of adriamycin nephropathy (AN). In the short-term AN model, iPS-MSCs conferred a substantial anti-apoptotic effect on tubular cells, associated with a downregulation of Bax and Bax/Bcl2 ratio and an upregulation of survivin expression. In vitro, conditioned medium from iPS-MSCs (iPSMSC-CM) significantly limited albumin-induced tubular apoptosis and enhanced tubular proliferation, accompanied by a reduced expression of tubular Bax and an elevated expression of Bcl2 and survivin. Oxidative stress was markedly attenuated by iPS-MSCs both in AN mice and in protein-overloaded tubular cells. In the long-term AN model, repeated injections of iPS-MSCs significantly inhibited tubulointerstitial fibrosis and reduced intrarenal deposition of collagen I, collagen IV and αSMA. Modulation of the hedgehog signaling pathway contributed to the anti-fibrotic effect of iPS-MSCs in chronic AN. Finally, we detected that most of the infused iPS-MSCs were entrapped in the lungs. In conclusion, our data support a beneficial role of iPS-MSCs in both acute and chronic AN.

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Section: Discussionmentioning

confidence: 99%

Human induced pluripotent stem cell-derived mesenchymal stem cells prevent adriamycin nephropathy in mice

Yiu

Wong

et al. 2017

Oncotarget

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“…Based on NS is a manifestation of cGVHD, MSCs were administered to this patient who failed first- and second-line therapy, and she eventually obtained CR. It has been reported that MSCs may ameliorate disease in rats with minimal change NS ( 9 ) and reduce acute rejection in patients who undergo renal transplantation ( 10 ). To our knowledge, this is the first report of MSCs as a treatment for NS in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells May Ameliorate Nephrotic Syndrome Post-Allogeneic Hematopoietic Stem Cell Transplantation-Case Report

et al. 2017

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IntroductionBecause of their immunomodulatory and anti-inflammatory effects, mesenchymal stem cells (MSCs) have been considered as potential therapeutic agents for treating immune-related or autoimmune diseases, such as graft-versus-host disease (GVHD). Nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an uncommon complication with unclear etiology and pathogenesis. It may be an immune disorder involving immune complex deposition, B cells, regulatory T cells (Tregs), and Th1 cytokines and be a manifestation of chronic GVHD. Corticosteroids and calcium antagonists, alone or in combination, are the most common therapeutic agents in this setting. Rituximab is commonly administered as salvage treatment. However, treatment failure and progressive renal function deterioration has been reported to occur in approximately 20% of patients in a particular cohort.Case presentationWe present a patient who developed NS 10 months after allo-HSCT. After treatment failure with cyclosporine A, prednisone, and rituximab, she achieved a complete response with MSC treatment. The clinical improvement of this patient was accompanied by a decreased B cell population together with an increased frequency of regulatory B cells (Bregs) and Tregs after MSC treatment.ConclusionMSCs could modulate NS after allo-HSCT by suppressing B cell proliferation, inducing Tregs and Bregs, and inhibiting inflammatory cytokine production by monocytes and NK cells. Among all these, Bregs might play an important role in ameliorating the NS of this patient.

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“…MSC or their secretome limit apoptosis and oxidative stress 9-13 of tubular cells, promote cell proliferation 9-14 and trafficking of mitochondria between adjacent tubular cells, 15 eventually accelerating renal repair 15,16 and preventing renal disease progression 17 in experimental models of acute kidney injury induced by cisplatin, 9-11 glycerol 12 or by ischemia/reperfusion injury. 13,18 MSC inhibit endothelial cell injury and increase capillary vessel density, 10,19,20 reduce podocyte apoptosis and preserve the expression of slit diaphragm proteins, [21][22][23][24] limit interstitial fibrosis 25 40 converting them into regulatory cells, [45][46][47][48] eventually prolonging murine kidney allograft survival, [49][50][51] and decreasing proteinuria and autoantibody production, 41,42 and prolonging life-span in lupus nephritis models. 43 Not registered (phase 1) 67 An intravenous injection n=20 -patients with CKD Placebo-controlled Safety and feasibility.…”

Section: Figure 1 Mesenchymal Stromal Cells (Msc) Actions On Renal and Inflammatory Cells In Kidney Disease And Transplantmentioning

confidence: 99%

“…MSC or their secretome limit apoptosis and oxidative stress 9-13 of tubular cells, promote cell proliferation 9-14 and trafficking of mitochondria between adjacent tubular cells,15 eventually accelerating renal repair15,16 and preventing renal disease progression17 in experimental models of acute kidney injury induced by cisplatin, 9-11 glycerol12 or by ischemia/reperfusion injury 13,18. MSC inhibit endothelial cell injury and increase capillary vessel density, 10,19,20 reduce podocyte apoptosis and preserve the expression of slit diaphragm proteins,[21][22][23][24] limit interstitial fibrosis25 by decreasing collagen, fibronectin and a-SMA expression and deposition,[26][27][28] reduce inflammatory cell infiltration 23,25,29-31 and expression of pro-inflammatory cytokines. Thus, MSC hinder pathological renal structural alteration and preserve renal function in CKD, chronic kidney disease models, such as subtotal nephrectomy,25 ureteral obstruction,26,27,32 renal artery stenosis, 19,20 diabetes 23,24,29-31 and adriamycin-induced nephropathy proteins 21,22.…”

mentioning

confidence: 99%

“…MSC inhibit endothelial cell injury and increase capillary vessel density, 10,19,20 reduce podocyte apoptosis and preserve the expression of slit diaphragm proteins,[21][22][23][24] limit interstitial fibrosis25 by decreasing collagen, fibronectin and a-SMA expression and deposition,[26][27][28] reduce inflammatory cell infiltration 23,25,29-31 and expression of pro-inflammatory cytokines. Thus, MSC hinder pathological renal structural alteration and preserve renal function in CKD, chronic kidney disease models, such as subtotal nephrectomy,25 ureteral obstruction,26,27,32 renal artery stenosis, 19,20 diabetes 23,24,29-31 and adriamycin-induced nephropathy proteins 21,22. In addition, MSC inhibit the activation and effector function of T cells,[33][34][35][36] dendritic cells, 37,38 macrophages 39 and B cells,40 converting them into regulatory cells,[45][46][47][48] eventually prolonging murine kidney allograft survival,[49][50][51] and decreasing proteinuria and autoantibody production,41,42 and prolonging life-span in lupus nephritis models 43,44.…”

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confidence: 99%

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Mesenchymal stromal cell-based therapy in kidney diseases and transplantation

Casiraghi

2019

Ital J Med

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Intense investigation in pre-clinical models of kidney disease and transplantation showed that mesenchymal stromal cell (MSC) therapy acts on renal and inflammatory cells in multiple, complex and integrated ways, resulting in cell repair and regeneration, in the inhibition of inflammatory cells, and in the development of cells endowed with their own anti-inflammatory and immuneregulatory properties. These encouraging data paved the way for exploring the use of MSC in clinics as innovative therapeutic tools for patients with renal diseases and transplantation. In this review, we describe the available results of clinical studies of MSC in patients with post-cardiac surgery, acute kidney injury, chronic kidney diseases - including diabetes, renovascular disease and lupus nephritis - and in kidney transplant recipients, with a particular focus on our experience with MSC therapy as a pro-tolerogenic strategy in kidney transplantation. The available studies, mainly phase 1, indicated that MSC therapy is safe and feasible and not associated with adverse events, at least in the short- and mid-term. Encouraging results have been reported in renovascular disease and kidney transplantation, while studies in acute kidney injury and chronic kidney disease had contrasting outcomes. The relevant issues and the knowledge gap that still limit the translation of MSC cell therapy into clinical practice are discussed briefly.

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Protective effects of mesenchymal stromal cells on adriamycin-induced minimal change nephrotic syndrome in rats and possible mechanisms

Cited by 15 publications

References 51 publications

Human induced pluripotent stem cell-derived mesenchymal stem cells prevent adriamycin nephropathy in mice

Human induced pluripotent stem cell-derived mesenchymal stem cells prevent adriamycin nephropathy in mice

Mesenchymal Stem Cells May Ameliorate Nephrotic Syndrome Post-Allogeneic Hematopoietic Stem Cell Transplantation-Case Report

Mesenchymal stromal cell-based therapy in kidney diseases and transplantation

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