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VEGF is a mediator of the renoprotective effects of multipotent marrow stromal cells in acute kidney injury.

Tögel F, Zhang P, Hu Z, Westenfelder C - J. Cell. Mol. Med. (2008)

Bottom Line: Knockdown of vascular enthothelial growth factor (VEGF) by siRNA reduced effectiveness of MSCs in the treatment of ischemic AKI in a rat model.Animals treated with MSCs had increased renal microvessel density compared to VEGF knockdown MSC-treated and vehicle-treated animals.These results show that VEGF is an important mediator of the early and late phase of renoprotective action after AKI in the context of stem cell treatment.

View Article: PubMed Central - PubMed

Affiliation: University of Utah, Division of Nephrology, Department of Medicine, Salt Lake City, UT 84148, USA.

ABSTRACT
Adult stem cell treatment of complex disorders is a promising therapeutic approach and multipotent marrow stromal cells (MSCs) have been shown to be effective in various animal models of diseases. Acute kidney injury (AKI) is a common and serious problem in hospitalized patients and bone marrow derived multipotent MSCs have been shown to be effective in different models of AKI. The mechanism of action of MSCs is complex but involves paracrine actions including growth factor secretion. Knockdown of vascular enthothelial growth factor (VEGF) by siRNA reduced effectiveness of MSCs in the treatment of ischemic AKI in a rat model. Animals treated with MSCs had increased renal microvessel density compared to VEGF knockdown MSC-treated and vehicle-treated animals. These results show that VEGF is an important mediator of the early and late phase of renoprotective action after AKI in the context of stem cell treatment.

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Related in: MedlinePlus

In vivo study to determine the effect of VEGF knockdown on therapeutic effectiveness in an ischemia/reperfusion model of AKI in rats. Left panel: Regular MSCs (grey bars) were renoprotective and enhance recovery from AKI in rats compared to VEGF knockdown MSCs (black bars). Right panel: Survival was increased in animals treated with wild type MSCs compared to VEGF knockdown MSCs (P < 0.05; n= 8).
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f3: In vivo study to determine the effect of VEGF knockdown on therapeutic effectiveness in an ischemia/reperfusion model of AKI in rats. Left panel: Regular MSCs (grey bars) were renoprotective and enhance recovery from AKI in rats compared to VEGF knockdown MSCs (black bars). Right panel: Survival was increased in animals treated with wild type MSCs compared to VEGF knockdown MSCs (P < 0.05; n= 8).

Mentions: In order to investigate the applicability of our in vitro results to the in vivo situation, we studied the comparative renoprotective effects of wild type MSCs and to VEGF knockdown MSCs in the standard model of ischemia/reperfusion AKI. Female SD rats were subjected to 48 min. of bilateral renal pedicle clamping to induce severe AKI. Regular MSCs were renoprotective as shown by lower serum creatinine values on days 1 and 7 compared to vehicle injection (Fig. 3A). VEGF knockdown rendered MSCs less effective in exerting renoprotection and recovery, which was highly significant at day 7 (P= 0.0004). Survival of animals treated with VEGF knockdown MSCs during the first three days after clamping was lower compared to MSC treated animals (Fig. 2B).


VEGF is a mediator of the renoprotective effects of multipotent marrow stromal cells in acute kidney injury.

Tögel F, Zhang P, Hu Z, Westenfelder C - J. Cell. Mol. Med. (2008)

In vivo study to determine the effect of VEGF knockdown on therapeutic effectiveness in an ischemia/reperfusion model of AKI in rats. Left panel: Regular MSCs (grey bars) were renoprotective and enhance recovery from AKI in rats compared to VEGF knockdown MSCs (black bars). Right panel: Survival was increased in animals treated with wild type MSCs compared to VEGF knockdown MSCs (P < 0.05; n= 8).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4940776&req=5

f3: In vivo study to determine the effect of VEGF knockdown on therapeutic effectiveness in an ischemia/reperfusion model of AKI in rats. Left panel: Regular MSCs (grey bars) were renoprotective and enhance recovery from AKI in rats compared to VEGF knockdown MSCs (black bars). Right panel: Survival was increased in animals treated with wild type MSCs compared to VEGF knockdown MSCs (P < 0.05; n= 8).
Mentions: In order to investigate the applicability of our in vitro results to the in vivo situation, we studied the comparative renoprotective effects of wild type MSCs and to VEGF knockdown MSCs in the standard model of ischemia/reperfusion AKI. Female SD rats were subjected to 48 min. of bilateral renal pedicle clamping to induce severe AKI. Regular MSCs were renoprotective as shown by lower serum creatinine values on days 1 and 7 compared to vehicle injection (Fig. 3A). VEGF knockdown rendered MSCs less effective in exerting renoprotection and recovery, which was highly significant at day 7 (P= 0.0004). Survival of animals treated with VEGF knockdown MSCs during the first three days after clamping was lower compared to MSC treated animals (Fig. 2B).

Bottom Line: Knockdown of vascular enthothelial growth factor (VEGF) by siRNA reduced effectiveness of MSCs in the treatment of ischemic AKI in a rat model.Animals treated with MSCs had increased renal microvessel density compared to VEGF knockdown MSC-treated and vehicle-treated animals.These results show that VEGF is an important mediator of the early and late phase of renoprotective action after AKI in the context of stem cell treatment.

View Article: PubMed Central - PubMed

Affiliation: University of Utah, Division of Nephrology, Department of Medicine, Salt Lake City, UT 84148, USA.

ABSTRACT
Adult stem cell treatment of complex disorders is a promising therapeutic approach and multipotent marrow stromal cells (MSCs) have been shown to be effective in various animal models of diseases. Acute kidney injury (AKI) is a common and serious problem in hospitalized patients and bone marrow derived multipotent MSCs have been shown to be effective in different models of AKI. The mechanism of action of MSCs is complex but involves paracrine actions including growth factor secretion. Knockdown of vascular enthothelial growth factor (VEGF) by siRNA reduced effectiveness of MSCs in the treatment of ischemic AKI in a rat model. Animals treated with MSCs had increased renal microvessel density compared to VEGF knockdown MSC-treated and vehicle-treated animals. These results show that VEGF is an important mediator of the early and late phase of renoprotective action after AKI in the context of stem cell treatment.

Show MeSH
Related in: MedlinePlus