Mesenchymal stem cell injection ameliorates chronic renal failure in a rat model

Villanueva, Sandra; Ewertz, Ernesto; Carrión, Flavio; Tapia, Andrés; Vergara, César; Céspedes, Carlos L.; Sáez, Pablo J.; Luz, P. A. C.; Irarrázabal, Carlos E.; Carreño, Juan; Figueroa, Fernando; Vío, Carlos P.

doi:10.1042/cs20110108

Cited by 73 publications

(76 citation statements)

References 51 publications

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“…Dosing was based on similar published manuscripts. 12,13 Sections of bladder tissue were fixed in 4% paraformaldehyde. Paraffin blocks were prepared with xylene and alcohol, washed with phosphate-buffered saline (PBS), and mounted using 4-feet 6-diamidino-2-phenylindole (DAPI) containing mounting-solution (ProLong Gold Antifade mounting medium, Invitrogen, ON, Canada).…”

Section: Methodsmentioning

confidence: 99%

Benefits of mesenchymal stem cells after partial bladder outlet obstruction

Al-Saikan

Ding

Tredget

et al. 2016

CUAJ

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Introduction: Partial bladder outlet obstruction (pBOO) results in significant morbidity and mortality in the pediatric and adult populations. Mesenchymal stem cells (MSC) have been widely studied in many organ systems for the treatment and prevention of fibrotic and inflammatory conditions. Therefore, we hypothesize that systemic administration of MSC will demonstrate short-term biochemical, histological, and urodynamic benefits in an animal model for pBOO. Methods: After University ethics approval, 5 x 106 green fluorescent protein GFP-labeled MSC were intravenously injected concurrently with pBOO in adult Sprague-Dawley rats. Five groups (n=3/ group) were analyzed: a) unobstructed controls; b) pBOO for seven days with intravenous MSC (7d+MSC); c) pBOO for seven days without intravenous MSC (7d-MSC); d) pBOO for 14 days with intravenous MSC (14d+MSC), e) pBOO for 14 days without MSC (14d-MSC). Urodynamics were performed at the end of the experimental period and bladders were weighed. Immunohistochemistry was performed for GFP detection and reverse transcription polymerase chain reaction (RT-PCR) to detect mRNA of: TGF-B, HIF-1a, RhoA, GRP-78, lumican, and decorin. Results: All animals remained healthy. GFP was detected in all treatment groups. MSC treatment resulted in a significant decrease in bladder capacity (0.91 cc vs. 2.15 cc, p=0.04). Treatment also resulted in significant decreases in mRNA levels of: TGF-B, HIF-1a, Rho-A, and GRP-78. Conclusions: Systemic treatment with MSC was well tolerated and resulted in MSC accumulation after pBOO. Despite our low numbers, we were able to successfully demonstrate short-term urodynamic improvements and widespread, significant decreases in inflammatory mediators. We believe that this decreased inflammatory cascade will help prevent long-term detrusor deterioration.

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Section: Methodsmentioning

confidence: 99%

Benefits of mesenchymal stem cells after partial bladder outlet obstruction

Al-Saikan

Ding

Tredget

et al. 2016

CUAJ

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“…In an eff ort to address the mechanisms involved in the amelioration of renal disease induced by MSCs, we recently evaluated several functional and molecular markers of kidney damage and regeneration in rats subjected to 5/6 nephrectomy (NPX) (Villanueva et al, 2011). In this well known model of chronic kidney disease, a single intravenous infusion of 0.5×10 6 MSCs was associated with significant reduction of serum creatinine and infl ammatory markers including macrophage infi ltration and interstitial α-SMA (α-smooth muscle actin).…”

Section: Msc Paracrine Factors In the Repair Mechanismmentioning

confidence: 99%

Mesenchymal Stem Cell treatment for autoimmune diseases: a critical review

et al. 2012

Self Cite

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Mesenchymal stem cells (MSCs) are now known to display not only stem cell multipotency, but also robust antiinfl ammatory and regenerative properties. After widespread in-vitro and in-vivo preclinical testing, autologous and allogeneic MSCs have been applied in a range of immune mediated conditions, including graft versus host disease, Crohn´s disease, multiple sclerosis, refractory systemic lupus erythematosus and systemic sclerosis. Current data suggests that MSCs may not only replace diseased tissues, but also exert several trophic, regenerative and antiinfl ammatory eff ects. While the clinical outcome in case reports and phase I-II trials seems occasionally striking, these limited results point to the need to perform controlled multicenter trials. Future advances from stem cell science can be expected to pinpoint signifi cant MSC subpopulations and/or stem cell markers for improved regenerative or immunoregulatory properties.

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“…A number of studies have hypothesised that certain growth factors or specific hormones, including HGF, EGF and IGF-1, are able to promote this transformation process, and accelerate the differentiation of nascent epithelial cells (30)(31)(32). In addition, several scholars have demonstrated that BMSCs are able to secrete a number of cytokines, thereby promoting the proliferation and repair of the endogenous renal tubular epithelial cells (33,34).…”

Section: Discussionmentioning

confidence: 99%

Effect of bone marrow stem cell mobilisation on the expression levels of cellular growth factors in a rat model of acute tubular necrosis

Bi¹,

Hou²,

Da-sheng³

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to observe the mobilisation effects of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) on bone marrow stem cells (BMSCs) in rats with renal ischaemia-reperfusion injury. In addition, the effects of the BMSCs on the expression levels of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) were investigated, with the aim to further the understanding of the protective mechanisms of SCF and G-CSF in renal ischaemia-reperfusion injury. The model and treatment groups were established using a model of unilateral renal ischaemia-reperfusion injury, in which the treatment group and the treatment control group were subcutaneously injected once a day with 200 µg/kg SCF and 50 µg/kg G-CSF, 24 h after the modelling, for five consecutive days. The CD34 + cell count was measured in the peripheral blood using flow cytometry. The mRNA expression levels of HGF and EGF were determined using polymerase chain reaction analysis, while the protein expression levels of HGF and EGF were detected using immunohistochemistry. The CD34 + cell count in the peripheral blood of the treatment and treatment control groups was significantly higher compared with that in the model group (P<0.05). However, CD34 expression levels in the cells from the renal tissues of the model and treatment groups were significantly higher compared with that of the control and treatment control groups (P<0.05), with the greatest increase observed in the treatment group. The mRNA and protein expression levels of HGF and EGF in the treatment group were significantly higher compared with the model group (P<0.05). Therefore, the results indicated that a combination of SCF and G-CSF can promote the repair of acute tubular necrosis. This combination, which can mobilise sufficient numbers of BMSCs to migrate back to the injured site, is a key factor in promoting the repair of renal tubular injury. Upregulation of HGF and EGF was also shown to promote the repair of renal tubular injury.

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Mesenchymal stem cell injection ameliorates chronic renal failure in a rat model

Cited by 73 publications

References 51 publications

Benefits of mesenchymal stem cells after partial bladder outlet obstruction

Benefits of mesenchymal stem cells after partial bladder outlet obstruction

Mesenchymal Stem Cell treatment for autoimmune diseases: a critical review

Effect of bone marrow stem cell mobilisation on the expression levels of cellular growth factors in a rat model of acute tubular necrosis

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