Intravenous injection of mesenchymal stem cells is effective in treating liver fibrosis

Zhao, Wei; Liu, Jun-Jie; Cao, Da-Yong; Li, Xiao; Zhang, Linying; He, Yong; Yue, Shu-Qiang; Wang, Desheng; Dou, Kefeng

doi:10.3748/wjg.v18.i10.1048

Cited by 129 publications

(102 citation statements)

References 39 publications

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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%

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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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Section: Discussionmentioning

confidence: 99%

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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show abstract

“…We identified eGFP DNA in the lungs and liver after systemic infusion of FVB-GFP MSCs to mice with and without arthritis. MSCs have been shown to engraft to lung and liver and this is to be expected due to the high circulating blood volume in these organs [48][49][50]. During active inflammation, hepatocytes become upregulated and increase production of acute phase proteins [51] leading to the hypothesis that the increased hepatocyte activity may generate chemoattractants for MSCs.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic Murine Mesenchymal Stem Cells: Migration to Inflamed Joints In Vivo and Amelioration of Collagen Induced Arthritis When Transduced to Express CTLA4Ig

Sullivan

Barry

Ritter

et al. 2013

Stem Cells and Development

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“…Carboxy fluorescein diacetate succinimidyl ester (CFSE) 39 and 4,6-diamidino-2-phenylindole, dihydrochloride (DAPI), 24 chloromethylbenzamidodialkylcarbocyanine (CM-Dil) 40 fluorescent dyes are commonly used to examine cell localization. The red fluorochrome PKH26, which mainly binds to the cell membrane, is an efficient cell tracer to locate transplanted cells.…”

Section: Tracing Of Transplanted Cellsmentioning

confidence: 99%

“…17 Injection of doses between 0.5-1 mL/kg CCl4 dissolved in olive [18][19][20] or corn oil 5,21 twice a week for 4-8 weeks 18,22 have been used for liver injury in small animal models. 12,20 CCl4 can be injected to rodents intraperitoneally 12,23,24 or subcutaneously. 5,18,20,21 Paracetamol, 25 ally alcohol (AA) 26 and dimethylnitroseamine (DMN) are other chemical agents for inducing liver damage in rodents.…”

Section: Introductionmentioning

confidence: 99%

Methods of Liver Stem Cell Therapy in Rodents as Models of Human Liver Regeneration in Hepatic Failure

Goradel¹,

Darabi²,

Shamsasenjan³

et al. 2015

Adv Pharm Bull

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Intravenous injection of mesenchymal stem cells is effective in treating liver fibrosis

Abstract: MSC administration is able to protect against liver fibrosis. Intravenous injection is the most favorable treatment modality through promotion of IL10 expression.

Cited by 129 publications

References 39 publications

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

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

Allogeneic Murine Mesenchymal Stem Cells: Migration to Inflamed Joints In Vivo and Amelioration of Collagen Induced Arthritis When Transduced to Express CTLA4Ig

Methods of Liver Stem Cell Therapy in Rodents as Models of Human Liver Regeneration in Hepatic Failure

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