Intraparenchymal Injection of Bone Marrow Mesenchymal Stem Cells Reduces Kidney Fibrosis after Ischemia-Reperfusion in Cyclosporine-Immunosuppressed Rats

Alfarano, Chiara; Roubeix, Christophe; Chaaya, Rana; Ceccaldi, Caroline; Calise, Denis; Mias, Céline; Cussac, Daniel; Bascands, Jean-Loup; Parini, Angelo

doi:10.3727/096368912x640448

Cited by 79 publications

(73 citation statements)

References 46 publications

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“…In rodent models, MSCs retard the progression of CKD by suppressing fibrosis. [37][38][39] Our study confirmed this effect and further demonstrated that MSC therapy with CS-IGF-1C hydrogel showed increased attenuation of fibrosis by substantially inhibiting expression of MMPs; this has been implicated in initiation and progression of renal fibrosis through epithelialmesenchymal transition as well as activation of fibroblasts. 40 Concordantly, cotransplantation of ADSCs and CS-IGF-1C hydrogel led to downregulated expression of a range of profibrotic genes, such as TGF-b, collagen type 1 a1, and fibronectin, in addition to increased expression of antifibrotic genes after AKI.…”

Section: Discussionsupporting

confidence: 75%

IGF-1 C Domain–Modified Hydrogel Enhances Cell Therapy for AKI

Feng

Zhang

Yang³

et al. 2016

JASN

107

135

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Low cell retention and engraftment after transplantation limit the successful application of stem cell therapy for AKI. Engineered microenvironments consisting of a hydrogel matrix and growth factors have been increasingly successful in controlling stem cell fate by mimicking native stem cell niche components. Here, we synthesized a bioactive hydrogel by immobilizing the C domain peptide of IGF-1 (IGF-1C) on chitosan, and we hypothesized that this hydrogel could provide a favorable niche for adipose-derived mesenchymal stem cells (ADSCs) and thereby enhance cell survival in an AKI model. In vitro studies demonstrated that compared with no hydrogel or chitosan hydrogel only, the chitosan-IGF-1C hydrogel increased cell viability through paracrine effects. In vivo, cotransplantation of the chitosan-IGF-1C hydrogel and ADSCs in ischemic kidneys ameliorated renal function, likely by the observed promotion of stem cell survival and angiogenesis, as visualized by bioluminescence imaging and attenuation of fibrosis. In conclusion, IGF-1C immobilized on a chitosan hydrogel provides an artificial microenvironment for ADSCs and may be a promising therapeutic approach for AKI.

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Section: Discussionsupporting

confidence: 75%

IGF-1 C Domain–Modified Hydrogel Enhances Cell Therapy for AKI

Feng

Zhang

Yang³

et al. 2016

JASN

107

135

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“…19 Furthermore, several animal studies determined that the administration of mesenchymal-derived stem cells significantly reduced fibrosis in the lung, kidney, and liver. [12][13][14] There are, however, no reports of stem cell-based therapy in the clinical management of urethral stricture disease. Our study is a proofof-concept study that demonstrates that local injection of ADSCs prevents fibrosis induced by TGF-β1 injection.…”

Section: Discussionmentioning

confidence: 99%

“…11 Furthermore, a number of animal studies have demonstrated that mesenchymal stem cells have antifibrotic properties that can reduce fibrosis in the lung, kidney, and liver. [12][13][14] We sought to evaluate the potential therapeutic benefits of adipose-derived stem cell (ADSCs) therapy in decreasing fibrotic tissue in a rat model of urethral fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Effect of adipose tissue-derived stem cell injection in a rat model of urethral fibrosis

Sangkum

Yafi

Kim³

et al. 2016

CUAJ

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Introduction: We sought to evaluate the therapeutic effect of adipose tissue-derived stem cells (ADSCs) in a rat model of urethral fibrosis. Methods: Eighteen (18) male Sprague-Dawley rats (300-350 g) were divided into three groups: (1) sham (saline injection); (2) urethral fibrosis group (10 μg transforming growth factor beta 1 (TGF-β1) injection); and (3) ADSCs group (10 μg TGF-β1 injection plus 2 x 10 5 ADSCs). Rat ADSCs were harvested from rat inguinal fat pads. All study animals were euthanized at two weeks after urethral injection. Following euthanasia, rat urethral tissue was harvested for histologic evaluation. Type I and III collagen levels were quantitated by Western blot analysis. Results: TGF-β1 injection induced significant urethral fibrosis and increased collagen type I and III expression (p<0.05). Significant decrease in submucosal fibrosis and collagen type I and III expression were noted in the ADSCs group compared with the urethral fibrosis group (p<0.05). TGF-β1 induced fibrotic changes were ameliorated by injection of ADSCs. Conclusions: Local injection of ADSCs in a rat model of urethral fibrosis significantly decreased collagen type I and III. These findings suggest that ADSC injection may prevent scar formation and potentially serve as an adjunct treatment to increase the success rate of primary treatment for urethral stricture disease. Further animal and clinical studies are needed to confirm these results. IntroductionUrethral stricture disease is a scarring process of the urethral mucosa and the surrounding spongy tissue of the corpus spongiosum.1 The reported estimated incidence of urethral stricture disease in an older veterans population is 0.6%.2 The incidence of urethral stricture diagnoses among Medicare beneficiaries was 1.4% in 1992 and 0.9% in 2001, respectively.3 Various modalities are available for the treatment of urethral strictures, including urethral dilatation, direct visual internal urethrotomy (DVIU), and various urethroplasty techniques. The long-term recurrencefree rates after DVIU and urethral dilatation remain quite poor. 4 Urethroplasty remains the standard of care for urethral strictures, but recurrence rates as high as 15.6% have been reported following surgery. 5 Factors predictive of treatment failure are not well-documented. 5 However, long stricture length (>4-5 cm), lichen sclerosus, infectious or iatrogenic etiologies, prior urethroplasty, and failed endoscopic therapy are risk factors of urethroplasty failure.6,7 Current adjunctive treatments that aim to improve treatment outcomes include injection of mitomycin c and steroids. [8][9][10] Results of these different treatment options remain inconsistent and, as such, none of these modalities have been widely adopted.Stem cells have the ability to undergo self-renewal and multilineage differentiation, and to form terminally differentiated cells.11 Furthermore, a number of animal studies have demonstrated that mesenchymal stem cells have antifibrotic properties that can reduce fibrosis in the lung, ki...

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“…Direct parenchymal injection allows efficient local delivery of MSCs and promotes the recovery of renal fuction. 29 However, the locally delivered MSCs tend to be confined to the injection site without diffusion to the whole kidney. Furthermore, this invasive method may cause bleeding and tissue destruction leading to secondary kidney damage and adverse effect on renal function recovery.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats

Wu¹,

Li²,

Gong³

et al. 2014

IJN

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Mesenchymal stem cell (MSC) therapy has been considered a promising strategy to cure diabetic nephropathy (DN). However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1) plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MB SDF-1 ) via covalent conjugation. The characterization and bioactivity of MB SDF-1 were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MB SDF-1 . The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24 hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8 μg/mL. MB SDF-1 remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24 hours compared with control treatments in normal rats and DN rats. In conclusion, ultrasound-targeted MB SDF-1 destruction could promote the homing of MSCs to early DN kidneys and provide a novel potential therapeutic approach for DN kidney repair.

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Intraparenchymal Injection of Bone Marrow Mesenchymal Stem Cells Reduces Kidney Fibrosis after Ischemia-Reperfusion in Cyclosporine-Immunosuppressed Rats

Cited by 79 publications

References 46 publications

IGF-1 C Domain–Modified Hydrogel Enhances Cell Therapy for AKI

IGF-1 C Domain–Modified Hydrogel Enhances Cell Therapy for AKI

Effect of adipose tissue-derived stem cell injection in a rat model of urethral fibrosis

Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats

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