Mesenchymal Stromal Cells Improve Renovascular Function in Polycystic Kidney Disease

Franchi, Federico; Peterson, Karen M.; Xu, Rende; Miller, Brent S.; Psaltis, Peter J.; Harris, Peter C.; Lerman, Lilach O.; Rodriguez-Porcel, Martin

doi:10.3727/096368914x684619

Cited by 27 publications

(25 citation statements)

References 51 publications

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“…MSCs have become a promising source for cell-based therapies (32,33). It has been reported that the co-culture of islets with MSCs has beneficial effects, including maintaining morphological changes, conserving islet function and preventing an early inflammatory reaction (34,35).…”

Section: Discussionmentioning

confidence: 99%

A new scaffold containing small intestinal submucosa and mesenchymal stem cells improves pancreatic islet function and survival in vitro and in vivo

Wang

Ding

Xue

et al. 2016

International Journal of Molecular Medicine

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It is unknown whether a scaffold containing both small intestinal submucosa (SIS) and mesenchymal stem cells (MSCs) for transplantation may improve pancreatic islet function and survival. In this study, we examined the effects of a SIS-MSC scaffold on islet function and survival in vitro and in vivo. MSCs and pancreatic islets were isolated from Sprague-Dawley rats, and SIS was isolated from Bamei pigs. The islets were apportioned among 3 experimental groups as follows: SIS-islets, SIS-MSC-islets and control-islets. In vitro, islet function was measured by a glucose-stimulated insulin secretion test; cytokines in cultured supernatants were assessed by enzyme-linked immunosorbent assay; and gene expression was analyzed by reverse transcription-quantitative PCR. In vivo, islet transplantation was performed in rats, and graft function and survival were monitored by measuring the blood glucose levels. In vitro, the SIS-MSC scaffold was associated with improved islet viability and enhanced insulin secretion compared with the controls, as well as with the increased the expression of insulin 1 (Ins1), pancreatic and duodenal homeobox 1 (Pdx1), platelet endothelial cell adhesion molecule 1 [Pecam1; also known as cluster of differentiation 31 (CD31)] and vascular endothelial growth factor A (Vegfa) in the islets, increased growth factor secretion, and decreased tumor necrosis factor (TNF) secretion. In vivo, the SIS-MSC scaffold was associated with improved islet function and graft survival compared with the SIS and control groups. On the whole, our findings demonstrate that the SIS-MSC scaffold significantly improved pancreatic islet function and survival in vitro and in vivo. This improvement may be associated with the upregulation of insulin expression, the improvement of islet microcirculation and the secretion of cytokines.

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Section: Discussionmentioning

confidence: 99%

A new scaffold containing small intestinal submucosa and mesenchymal stem cells improves pancreatic islet function and survival in vitro and in vivo

Wang

Ding

Xue

et al. 2016

International Journal of Molecular Medicine

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“…In the last years, two studies have been published that show the possible therapeutic effects of allogeneic stem cells in rats. Franchi et al have shown that a single injection of BM-MSC isolated from healthy SD rats could improve the kidney function in PCK rats, partially restoring renal function ( 273 ). This study points out two of the potential effects of stem cells: the paracrine effects, by the release of cytokines, such as SDF1, VEGF, and HGF, and the ability of the cells, after injection, to acquire characteristics of endothelial cells, suggesting transdifferentiation of these cells.…”

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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“…Anti-apoptotic [ 10 ], anti-fibrotic [ 11 ], and anti-inflammatory [ 12 ] capabilities of MSCs [ 7 ] provide the basis for their administration to control the progression of polycystic kidney disease (PKD). Franchi et al have reported that transplanted MSCs restored kidney function in a PKD model and improved damaged vasculature of these kidneys [ 13 ]. Previously we showed the promising efficacy of transplanted MSCs in experimental models of chronic kidney disease (CKD) and acute kidney injury (AKI) [ 14 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

Safety and tolerability of autologous bone marrow mesenchymal stromal cells in ADPKD patients

et al. 2017

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BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is a genetic ciliopathy disease characterized by progressive formation and enlargement of cysts in multiple organs. The kidneys are particularly affected and patients may eventually develop end-stage renal disease (ESRD). We hypothesize that bone marrow mesenchymal stromal cells (BMMSCs) are renotropic and may improve kidney function via anti-apoptotic, anti-fibrotic, and anti-inflammatory effects. In this study, we aim to assess the safety and tolerability of a BMMSC infusion in ADPKD patients.MethodsWe performed a single-arm phase I clinical trial with a 12-month follow-up. This study enrolled six eligible ADPKD patients with an estimated glomerular filtration rate (eGFR) of 25–60 ml/min/1.73 m2. Patients received autologous cultured BMMSCs (2 × 106 cells/kg) through the cubital vein according to our infusion protocol. We investigated safety issues and kidney function during the follow-up visits, and compared the findings to baseline and 1 year prior to the intervention.ResultsThere were no patients lost to follow-up. We observed no cell-related adverse events (AE) and serious adverse events (SAE) after 12 months of follow-up. The mean eGFR value of 33.8 ± 5.3 ml/min/1.73 m2 1 year before cell infusion declined to 26.7 ± 3.1 ml/min/1.73 m2 at baseline (P = 0.03) and 25.8 ± 6.2 ml/min/1.73 m2 at the 12-month follow-up visit (P = 0.62). The mean serum creatinine (SCr) level of 2 ± 0.3 mg/dl 1 year before the infusion increased to 2.5 ± 0.4 mg/dl at baseline (P = 0.04) and 2.5 ± 0.6 mg/dl at the 12-month follow-up (P = 0.96). This indicated significant changes between the differences of these two periods (12 months before infusion to baseline, and 12 months after infusion to baseline) in SCr (P = 0.05), but not eGFR (P = 0.09).ConclusionsThis trial demonstrated the safety and tolerability of an intravenous transplantation of autologous BMMSCs. BMMSC efficacy in ADPKD patients should be investigated in a randomized placebo-controlled trial with a larger population, which we intend to perform.Trial registrationClinicalTrials.gov, NCT02166489. Registered on June 14, 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0557-7) contains supplementary material, which is available to authorized users.

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Mesenchymal Stromal Cells Improve Renovascular Function in Polycystic Kidney Disease

Cited by 27 publications

References 51 publications

A new scaffold containing small intestinal submucosa and mesenchymal stem cells improves pancreatic islet function and survival in vitro and in vivo

A new scaffold containing small intestinal submucosa and mesenchymal stem cells improves pancreatic islet function and survival in vitro and in vivo

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

Safety and tolerability of autologous bone marrow mesenchymal stromal cells in ADPKD patients

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