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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

Assessment of microvessel density in renal cortex sections of rats 4 weeks after AKI. (A) CD34 staining of renal vasculature without nuclear counterstaining. (B) Binary image of (A) made with ImageJ in order to automatically determine the area percentage of the stained vessels. (C) Calculated mean vascular area (percent of section) per visual field in the renal cortex. Three 20× field per section from every group (n= 5) were randomly chosen and averages are plotted. Animals treated with regular MSCs have a significantly higher vascular area compared to VEGF knockdown MSC treated animals and controls (vehicle treated).
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f4: Assessment of microvessel density in renal cortex sections of rats 4 weeks after AKI. (A) CD34 staining of renal vasculature without nuclear counterstaining. (B) Binary image of (A) made with ImageJ in order to automatically determine the area percentage of the stained vessels. (C) Calculated mean vascular area (percent of section) per visual field in the renal cortex. Three 20× field per section from every group (n= 5) were randomly chosen and averages are plotted. Animals treated with regular MSCs have a significantly higher vascular area compared to VEGF knockdown MSC treated animals and controls (vehicle treated).

Mentions: VEGF is the major mediator of vascular growth and repair and microvascular injury is an important pathophysiological component of AKI [15, 16]. Therefore, we determined renal microvessel density at 4 weeks after ischemia/reperfusion AKI in animals treated with regular MSCs and VEGF knockdown MSCs, using an immunostaining approach. Paraffin sections of kidneys were immunostained with CD34 to visualize the renal vasculature (Fig. 4A). No counterstaining was applied and all sections were examined the same way with ImageJ. Area percentage of staining from binary images (Fig. 4B) was determined with the ‘measure’ function. Animals treated with regular MSCs had a significantly higher percentage area of vasculature compared to animals treated with VEGF knockdown MSCs and vehicle treated animals (Fig. 4C; P < 0.001). Tissue injury (apoptosis/necrosis) was not determined at this time point since surviving animals had recovered from the acute phase of AKI and these data would not have added additional information.


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)

Assessment of microvessel density in renal cortex sections of rats 4 weeks after AKI. (A) CD34 staining of renal vasculature without nuclear counterstaining. (B) Binary image of (A) made with ImageJ in order to automatically determine the area percentage of the stained vessels. (C) Calculated mean vascular area (percent of section) per visual field in the renal cortex. Three 20× field per section from every group (n= 5) were randomly chosen and averages are plotted. Animals treated with regular MSCs have a significantly higher vascular area compared to VEGF knockdown MSC treated animals and controls (vehicle treated).
© Copyright Policy
Related In: Results  -  Collection

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

f4: Assessment of microvessel density in renal cortex sections of rats 4 weeks after AKI. (A) CD34 staining of renal vasculature without nuclear counterstaining. (B) Binary image of (A) made with ImageJ in order to automatically determine the area percentage of the stained vessels. (C) Calculated mean vascular area (percent of section) per visual field in the renal cortex. Three 20× field per section from every group (n= 5) were randomly chosen and averages are plotted. Animals treated with regular MSCs have a significantly higher vascular area compared to VEGF knockdown MSC treated animals and controls (vehicle treated).
Mentions: VEGF is the major mediator of vascular growth and repair and microvascular injury is an important pathophysiological component of AKI [15, 16]. Therefore, we determined renal microvessel density at 4 weeks after ischemia/reperfusion AKI in animals treated with regular MSCs and VEGF knockdown MSCs, using an immunostaining approach. Paraffin sections of kidneys were immunostained with CD34 to visualize the renal vasculature (Fig. 4A). No counterstaining was applied and all sections were examined the same way with ImageJ. Area percentage of staining from binary images (Fig. 4B) was determined with the ‘measure’ function. Animals treated with regular MSCs had a significantly higher percentage area of vasculature compared to animals treated with VEGF knockdown MSCs and vehicle treated animals (Fig. 4C; P < 0.001). Tissue injury (apoptosis/necrosis) was not determined at this time point since surviving animals had recovered from the acute phase of AKI and these data would not have added additional information.

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