Long-term Angiogenesis Efficacy Using a Heparin-Conjugated Fibrin (HCF) Delivery System with HBM-MSCs

Abstract

Background and Objectives: Heparin-conjugated fibrin (HCF) is suitable for the release and localization of bFGF. We analyzed the effects of a bFGF delivery system using HCF with human bone marrow-derived mesenchymal stem cells (HBM-MSCs) in a dog ischemic limb model. Methods and Results: Animals were divided into HBM-MSCs, HBM-MSCs＋HCF, bFGF-HCF, and HBM-MSCs＋ bFGF-HCF groups. A total of 1×10 7 HBM-MSCs were injected per animal, and the amount of bFGF was 1 mg per dog. Ischemic muscles were harvested at eight weeks and six months after injection of cells. The HBM-MSCs＋ bFGF-HCF group exhibited decreased proportions of capillaries and arterioles six months after transplantation. However, there were more cells positive for the angiogenic factors, VEGF and PDGF, in the eight-week specimens compared with those harvested six months after transplantation. Conclusions: Our results demonstrated that a single injection of HBM-MSCs did not have significant long-term angiogenic effects; however, a bFGF delivery system using HCF exerted prolonged angiogenic effects when combined with HBM-MSCs.

ETV2/ER71 Transcription Factor as a Therapeutic Vehicle for Cardiovascular Disease

“…More recently, another study in a swine model of MI reported that adenovirus carrying human SCF enhanced cardiac functions, with an increase of c-KIT + cells, vessel density, and a decrease in apoptosis 115. In a dog model of hindlimb ischemia, human bone marrow- derived mesenchymal stem cells together with the sustained release of bFGF via heparin-conjugated fibrin promoted the angiogenic effect, as indicated by the increased arterioles and capillaries, as well as PDGF- and VEGFA-positive cells 6 months after transplantation 116. Large animal models are essential, not only for their usefulness in translating preclinical results into clinical research, but also for determining optimal dosage and delivery route for human use 117.…”