VEGF is a mediator of the renoprotective effects of multipotent marrow stromal cells in acute kidney injury.
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.
Tögel
Florian
F
University of Utah, Division of Nephrology, Department of Medicine, Salt Lake City, UT, USA.|VA Medical Center, Section of Nephrology, Salt Lake City, UT, USA.
Zhang
Ping
P
University of Utah, Division of Nephrology, Department of Medicine, Salt Lake City, UT, USA.|VA Medical Center, Section of Nephrology, Salt Lake City, UT, USA.
Hu
Zhuma
Z
University of Utah, Division of Nephrology, Department of Medicine, Salt Lake City, UT, USA.|VA Medical Center, Section of Nephrology, Salt Lake City, UT, USA.
Westenfelder
Christof
C
University of Utah, Division of Nephrology, Department of Medicine, Salt Lake City, UT, USA.|VA Medical Center, Section of Nephrology, Salt Lake City, UT, USA.|Department of Physiology, University of Utah, Salt Lake City, UT, USA.
D000818:Animals; D001483:Base Sequence; D017077:Culture Media, Conditioned; D017931:DNA Primers; D004195:Disease Models, Animal; D005260:Female; D055785:Gene Knockdown Techniques; D007668:Kidney / Q000503:physiopathology*; D039902:Multipotent Stem Cells / Q000166:cytology*; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology*
D017077:Culture Media, Conditioned; D017931:DNA Primers; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A