Perivascular delivery of encapsulated mesenchymal stem cells improves postischemic angiogenesis via paracrine activation of VEGF-A

Katare, R., Riu, F., Rowlinson, J., Lewis, A., Holden, R., Meloni, M., Reni, C., Wallrapp, C., Emanueli, C. and Madeddu, P. (2013) Perivascular delivery of encapsulated mesenchymal stem cells improves postischemic angiogenesis via paracrine activation of VEGF-A. Arteriosclerosis, Thrombosis, and Vascular Biology, 33(8), pp. 1872-1880. (doi: 10.1161/ATVBAHA.113.301217)

Abstract

Objective—To test the therapeutic activity of perivascular transplantation of encapsulated human mesenchymal stem cells (MSCs) in an immunocompetent mouse model of limb ischemia.<p></p> Approach and Results—CD1 mice underwent unilateral limb ischemia, followed by randomized treatment with vehicle, alginate microbeads (MBs), MB-encapsulated MSCs (MB-MSCs), or MB-MSCs engineered with glucagon-like peptide-1. Treatments were applied directly in the perivascular space around the femoral artery. Laser Doppler and fluorescent microsphere assessment of blood flow showed a marked improvement of perfusion in the MB-MSCs and MB-MSCs engineered with glucagon-like peptide-1 groups, which was associated with increased foot salvage particularly in MB-MSCs engineered with glucagon-like peptide-1–treated mice. Histological analysis revealed increased capillary and arteriole density in limb muscles of the 2 MSC groups. Furthermore, MB-MSCs engineered with glucagon-like peptide-1 and, to a lesser extent, MB-MSC treatment increased functional arterial collaterals alongside the femoral artery occlusion. Analysis of expressional changes in ischemic muscles showed that MB-MSC transplantation activates a proangiogenic signaling pathway centered on vascular endothelial growth factor A. In contrast, intramuscular MB-MSCs caused inflammatory reaction, but no improvement of reparative vascularization. Importantly, nonencapsulated MSCs were ineffective either by intramuscular or perivascular route.<p></p> Conclusions—Perivascular delivery of encapsulated MSCs helps postischemic reperfusion. This novel biological bypass method might be useful in patients not amenable to conventional revascularization approaches.<p></p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Meloni, Dr Marco
• Authors: Katare, R., Riu, F., Rowlinson, J., Lewis, A., Holden, R., Meloni, M., Reni, C., Wallrapp, C., Emanueli, C., and Madeddu, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Arteriosclerosis, Thrombosis, and Vascular Biology
• Publisher: American Heart Association
• ISSN: 1079-5642
• ISSN (Online): 1524-4636