Genetic Modification of Mesenchymal Stem Cells to Overexpress <i>CXCR4</i> and <i>CXCR7</i> Does Not Improve the Homing and Therapeutic Potentials of These Cells in Experimental Acute Kidney Injury

Gheisari, Yousof; Azadmanesh, Kayhan; Ahmadbeigi, Naser; Nassiri, Seyed Mahdi; Golestaneh, Azadeh Fahim; Naderi, Mahmood; Vasei, Mohammad; Arefian, Ehsan; Samiee, Siamak Mirab; Shafiee, Abbas; Soleimani, Masoud; Zeinali, Sirous

doi:10.1089/scd.2011.0588

Cited by 47 publications

(29 citation statements)

References 57 publications

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“…29 However, its functional role in AKI remains uncertain. 30,31 Zaruba et al reported that pharmacologic inhibition of DPP-4 was able to increase the homing of SDF-1 receptor-positive endothelial progenitor cells at sites of myocardial damage in mice, thereby reducing cardiac remodeling, functional improvement, and survival. 32 However, plasma SDF-1 levels in mice treated by the DPP-4 inhibitor were lower than in untreated mice, indicating that plasma SDF-1 might play no role in renal protection by AG.…”

Section: Discussionmentioning

confidence: 99%

Protection of Glucagon-Like Peptide-1 in Cisplatin-Induced Renal Injury Elucidates Gut-Kidney Connection

Katagiri¹,

Hamasaki

Doi

et al. 2013

Journal of the American Society of Nephrology

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Accumulating evidence of the beyond-glucose lowering effects of a gut-released hormone, glucagon-like peptide-1 (GLP-1), has been reported in the context of remote organ connections of the cardiovascular system. Specifically, GLP-1 appears to prevent apoptosis, and inhibition of dipeptidyl peptidase-4 (DPP-4), which cleaves GLP-1, is renoprotective in rodent ischemia-reperfusion injury models. Whether this renoprotection involves enhanced GLP-1 signaling is unclear, however, because DPP-4 cleaves other molecules as well. Thus, we investigated whether modulation of GLP-1 signaling attenuates cisplatin (CP)-induced AKI. Mice injected with 15 mg/kg CP had increased BUN and serum creatinine and CP caused remarkable pathologic renal injury, including tubular necrosis. Apoptosis was also detected in the tubular epithelial cells of CP-treated mice using immunoassays for single-stranded DNA and activated caspase-3. Treatment with a DPP-4 inhibitor, alogliptin (AG), significantly reduced CP-induced renal injury and reduced the renal mRNA expression ratios of Bax/Bcl-2 and Bim/Bcl-2. AG treatment increased the blood levels of GLP-1, but reversed the CP-induced increase in the levels of other DPP-4 substrates such as stromal cell-derived factor-1 and neuropeptide Y. Furthermore, the GLP-1 receptor agonist exendin-4 reduced CP-induced renal injury and apoptosis, and suppression of renal GLP-1 receptor expression in vivo by small interfering RNA reversed the renoprotective effects of AG. These data suggest that enhancing GLP-1 signaling ameliorates CP-induced AKI via antiapoptotic effects and that this gut-kidney axis could be a new therapeutic target in AKI.

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Section: Discussionmentioning

confidence: 99%

Protection of Glucagon-Like Peptide-1 in Cisplatin-Induced Renal Injury Elucidates Gut-Kidney Connection

Katagiri¹,

Hamasaki

Doi

et al. 2013

Journal of the American Society of Nephrology

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“…Their results showed that overexpression of the CXCR4 gene enhanced BMSC migration to the kidney after AKI. However, Gheisari et al reported a different conclusion [28]. In their study, CXCR4 and CXCR7 were separately and simultaneously overexpressed in BMSCs with a lentiviral vector system, and the homing and renoprotective potentials of these cells were evaluated in the mouse model of cisplatin-induced AKI.…”

Section: Introductionmentioning

confidence: 96%

Administration of BMSCs with Muscone in Rats with Gentamicin-Induced AKI Improves Their Therapeutic Efficacy

et al. 2014

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The therapeutic action of bone marrow-derived mesenchymal stem cells (BMSCs) in acute kidney injury (AKI) has been reported by several groups. However, recent studies indicated that BMSCs homed to kidney tissues at very low levels after transplantation. The lack of specific homing of exogenously infused cells limited the effective implementation of BMSC-based therapies. In this study, we provided evidence that the administration of BMSCs combined with muscone in rats with gentamicin-induced AKI intravenously, was a feasible strategy to drive BMSCs to damaged tissues and improve the BMSC-based therapeutic effect. The effect of muscone on BMSC bioactivity was analyzed in vitro and in vivo. The results indicated that muscone could promote BMSC migration and proliferation. Some secretory capacity of BMSC still could be improved in some degree. The BMSC-based therapeutic action was ameliorated by promoting the recovery of biochemical variables in urine or blood, as well as the inhibition of cell apoptosis and inflammation. In addition, the up-regulation of CXCR4 and CXCR7 expression in BMSCs could be the possible mechanism of muscone amelioration. Thus, our study indicated that enhancement of BMSCs bioactivities with muscone could increase the BMSC therapeutic potential and further developed a new therapeutic strategy for the treatment of AKI.

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“…Many researchers come up with the paracrine hypothesis for the underlying mechanism, namely, the BMSCs can accelerate the recovery of erectile function by releasing a variety of growth factors [36,37] , including the vascular endothelial growth factor (VEGF), fibroblast growth factor-2, hepatocyte growth factor and insulin-like growth factor-1 [38] . VEGF is a cytokine that has been shown to stimulate endothelial cell growth and modulate angiogenesis, and can promote proliferation, delay senescence, suppress apoptosis and increase the survival of various cells types [10,39] .…”

Section: Discussionmentioning

confidence: 99%

B Cell Lymphoma-2-Modified Bone Marrow-Derived Mesenchymal Stem Cells Transplantation for the Treatment of Diabetes Mellitus-Induced Erectile Dysfunction in a Rat Model

Sun¹,

Luo²,

Feng³

et al. 2016

Urol Int

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Objective: The study aimed to explore the effects of B cell lymphoma-2 (Bcl-2)-modified bone marrow-derived mesenchymal stem cells (BMSCs) transplantation for the treatment of diabetes mellitus-induced erectile dysfunction (DMED) in a rat model. Methods: The DMED rat model was successfully established. Thirty-six DMED rats were assigned into the Bcl-2-BMSCs, null-BMSCs, BMSCs and phosphate buffered saline (PBS) groups. Meanwhile, 9 normal rats injected with PBS were taken as the normal control group. Results: In the Bcl-2-BMSCs group, the average times of erection, rate of erection, peak intra-cavernous pressure (ICP) and peak ICP/mean arterial pressure were higher than those in the null-BMSCs, BMSCs and PBS groups, but were lower than those in the normal control group. In the Bcl-2-BMSCs group, capillary vessels and Bcl-2 mRNA and protein expressions were similar to those in the normal control group, while they were higher than those in other groups. Conclusion: These findings indicate that Bcl-2-modified BMSC transplantation could improve erectile function in DMED rats.

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Genetic Modification of Mesenchymal Stem Cells to Overexpress CXCR4 and CXCR7 Does Not Improve the Homing and Therapeutic Potentials of These Cells in Experimental Acute Kidney Injury

Cited by 47 publications

References 57 publications

Protection of Glucagon-Like Peptide-1 in Cisplatin-Induced Renal Injury Elucidates Gut-Kidney Connection

Protection of Glucagon-Like Peptide-1 in Cisplatin-Induced Renal Injury Elucidates Gut-Kidney Connection

Administration of BMSCs with Muscone in Rats with Gentamicin-Induced AKI Improves Their Therapeutic Efficacy

B Cell Lymphoma-2-Modified Bone Marrow-Derived Mesenchymal Stem Cells Transplantation for the Treatment of Diabetes Mellitus-Induced Erectile Dysfunction in a Rat Model

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