Autocrine angiogenic vascular prosthesis with bone marrow transplantation

Abstract

Synthetic vascular prostheses are foreign bodies, so that blood coagulation can occur on their luminal surfaces, causing graft occlusion very frequently in prostheses of small diameter. A vascular prosthesis needs angiogenesis for endothelialization of the luminal surface, as endothelial cells have natural and permanent antithrombogenic properties. To induce capillary growth into the graft, we developed a method of transplanting bone marrow cells, which are primitive, strong enough to survive, and create blood cells, resulting in the inducement of capillary growth. In an animal experiment, marrow cells were infiltrated into the walls of long-fibril expanded polytetrafluoroethylene (ePTFE) vascular grafts. The grafts were implanted in the abdominal aortic position of 24 dogs autologously. Marrow cells survived and continued exogenous hemopoiesis for up to six months and were immunohistochemically reactive to basic fibroblast growth factor (bFGF). All the grafts older than three weeks had complete endothelialization and maintained their patency. Twenty grafts without bone marrow were implanted as controls. Endothelialization was present at anastomotic sites, but other areas were covered with fresh thrombi. Four out of seven control grafts were patent with endothelial cell lining at six months, but three were occluded and one of the four grafts was still covered with a thrombus layer. Bone marrow with its unique native properties produced autocrine angiogenicity in the graft.

Hemangioblasts, angioblasts, and adult endothelial cell progenitors

“…Elegant studies by Sauvage and colleagues showed that when blood flow is present, implanted synthetic arterial grafts can be reendothelialized even when endothelial cell ingrowth from the anastomoses and the vaso vasorum are apparently prevented (Shi et al, 1994;Wu et al, 1995). Another study found that when bone marrow cells were infiltrated into synthetic vascular grafts, endothelialization occurred more rapidly than in uninfiltrated controls (Noishiki et al, 1996). All of these studies pointed to the presence of hemangioblasts, endothelial cells, or their precursors in the blood and/or bone marrow and provided strong evidence for adult vasculogenesis.…”

First Evidence That Bone Marrow Cells Contribute to the Construction of Tissue-Engineered Vascular Autografts In Vivo

“…12 In light of these reports, we hypothesized that BMCs would contribute to histogenesis in TEVAs. To test this hypothesis, we seeded labeled BMCs onto a biodegradable scaffold, which was then implanted to the inferior vena cava (IVC) of dogs.…”

Current address: Shinji Tomita, MD, Cardiothoracic Surgical Unit, Level 4, Auckland City Hospital, Auckland, New Zealand

“…We used them as the candidate cell for transplantation and as a source of growth factors such as VEGF and b-FGF. 6,7 BMC can be taken easily and autologously. Hamano et al reported that the growth factor from BMC was enhanced under hypoxia, and induced angiogenesis.…”

“…There are several possible reasons for this result. We used BMC as the source of growth factors 6,7 that could induce angiogenesis. The capillary density of group 3 was the greatest in the comparison of all the groups, which suggests that the growth factor in the BMC is involved in the formation of capillary at the border of the damaged myocardium.…”