Systemically delivered adipose stromal vascular fraction cells disseminate to peripheral artery walls and reduce vasomotor tone through a CD11b+ cell-dependent mechanism.
Vasoactivity, an important aspect of tissue healing, is often compromised in disease and tissue injury. Dysfunction in the smaller vasoactive arteries is most impactful, given the role of these vessels in controlling downstream tissue perfusion. The adipose stromal vascular fraction (SVF) is a mix of homeostatic cells shown to promote tissue healing. Our objective was to test the hypothesis that autologous SVF cells therapeutically modulate peripheral artery vasoactivity in syngeneic mouse models of small artery function. Analysis of vasoactivity of saphenous arteries isolated from normal mice 1 week after intravenous injection of freshly isolated SVF cells revealed that pressure-dependent artery vasomotor tone was decreased by the SVF cell isolate, but not one depleted of CD11b(+) cells. Scavenging hydrogen peroxide in the vessel wall abrogated the artery relaxation promoted by the SVF cell isolate. Consistent with a CD11b(+) cell being the relevant cell type, SVF-derived F4/80-positive macrophages were present within the adventitia of the artery wall coincident with vasorelaxation. In a model of artery inflammation mimicking a common disease condition inducing vasoactive dysfunction, the SVF cells potentiated relaxation of saphenous arteries without structurally remodeling the artery via a CD11b(+) cell-dependent manner. Our findings demonstrate that freshly isolated, adipose SVF cells promote vasomotor relaxation in vasoactive arteries via a hydrogen peroxide-dependent mechanism that required CD11b(+) cells (most likely macrophages). Given the significant impact of small artery dysfunction in disease, we predict that the intravenous delivery of this therapeutic cell preparation would significantly improve tissue perfusion, particularly in diseases with diffuse vascular involvement.
Cardiovascular Innovation Institute, Department of Surgery, Department of Physiology and Biophysics, and Department of Radiology, University of Louisville, Louisville, Kentucky, USA; Christina M. Kleinert Institute, Louisville, Kentucky, USA.
Marvin E
ME
Morris
Cardiovascular Innovation Institute, Department of Surgery, Department of Physiology and Biophysics, and Department of Radiology, University of Louisville, Louisville, Kentucky, USA; Christina M. Kleinert Institute, Louisville, Kentucky, USA.
Jason E
JE
Beare
Cardiovascular Innovation Institute, Department of Surgery, Department of Physiology and Biophysics, and Department of Radiology, University of Louisville, Louisville, Kentucky, USA; Christina M. Kleinert Institute, Louisville, Kentucky, USA.
Robert M
RM
Reed
Cardiovascular Innovation Institute, Department of Surgery, Department of Physiology and Biophysics, and Department of Radiology, University of Louisville, Louisville, Kentucky, USA; Christina M. Kleinert Institute, Louisville, Kentucky, USA.
Jacob R
JR
Dale
Cardiovascular Innovation Institute, Department of Surgery, Department of Physiology and Biophysics, and Department of Radiology, University of Louisville, Louisville, Kentucky, USA; Christina M. Kleinert Institute, Louisville, Kentucky, USA.
Amanda J
AJ
LeBlanc
Cardiovascular Innovation Institute, Department of Surgery, Department of Physiology and Biophysics, and Department of Radiology, University of Louisville, Louisville, Kentucky, USA; Christina M. Kleinert Institute, Louisville, Kentucky, USA.
Christina L
CL
Kaufman
Cardiovascular Innovation Institute, Department of Surgery, Department of Physiology and Biophysics, and Department of Radiology, University of Louisville, Louisville, Kentucky, USA; Christina M. Kleinert Institute, Louisville, Kentucky, USA.
Huaiyu
H
Zheng
Cardiovascular Innovation Institute, Department of Surgery, Department of Physiology and Biophysics, and Department of Radiology, University of Louisville, Louisville, Kentucky, USA; Christina M. Kleinert Institute, Louisville, Kentucky, USA.
Chin K
CK
Ng
Cardiovascular Innovation Institute, Department of Surgery, Department of Physiology and Biophysics, and Department of Radiology, University of Louisville, Louisville, Kentucky, USA; Christina M. Kleinert Institute, Louisville, Kentucky, USA.
Stuart K
SK
Williams
Cardiovascular Innovation Institute, Department of Surgery, Department of Physiology and Biophysics, and Department of Radiology, University of Louisville, Louisville, Kentucky, USA; Christina M. Kleinert Institute, Louisville, Kentucky, USA jay.hoying@louisville.edu.
James B
JB
Hoying
D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001158:Arteries / Q000166:cytology* / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D017154:Stromal Cells / Q000166:cytology*; D014666:Vasomotor System / Q000378:metabolism*
D039481:CD11b Antigen; C509295:ITGAM protein, human
Adipose stromal vascular fraction; Cell therapy; Macrophage; Small artery; Vasomotor tone