EPCs-Collagen Sponge Complex Promotes Neovascularization of Chronic Cerebral Ischemia following Multiple Burr Hole (MBH) Surgery

Abstract

Objective: The aim of this study was to explore the effect of endothelial progenitor cells (EPCs)-collagen sponge complex on the neovascularization of chronic cerebral ischemia following multiple burr hole (MBH) surgery. Methods: Bone marrow-derived EPCs from 5 Fisher 344 (F344) inbred rats were cultured and amplified in vitro, then co-cultured to become the EPCs-collagen sponge complex. Chronic cerebral hypo-perfusion was induced in 30 inbred male F344 rats by permanent bilateral internal carotid artery occlusion (BICAO). The MBH operation was performed three days after BICAO surgery. Rats were then randomly divided into 3 groups (n=10 each group); EPCs-collagen sponge complex + MBH; collagen sponge + MBH and MBH group. Either EPCs-collagen sponge complex or collagen sponge was implanted at the burr hole site in the EPCs-collagen sponge complex + MBH and the collagen sponge + MBH group, respectively. Regional cerebral blood flow (rCBF) was measured by Laser Doppler Flowmetry (LDF), EPCs were tracked by fluorescein, and immune-histochemical analysis for the neovascularization was performed 21 days after MBH surgery. Results: Before the MBH surgery, no differences of rCBF between the EPCs-collagen sponge complex + MBH group, the collagen sponge + MBH group and the MBH alone group (P>0.05) were found. The increase of rCBF in the EPCs-collagen sponge complex + MBH group (20.29 ± 10.21%) was significantly higher when compared with the other two groups 21 days after MBH surgery (7.39 ± 6.85% and 10.32 ± 6.27%, respectively; P<0.05). The amount of new blood vessels in the EPCs-collagen sponge complex + MBH group was also significantly greater than the other two groups (78.2 ± 4.7 vs. 48.7 ± 6.1 vs. 46.9 ± 7.3; P<0.05). The labeled EPCs were incorporated into the endothelial cells of vessels at the burr hole sites. Conclusion: The EPCs-collagen sponge complex enhances angiogenesis after MBH surgery under chronic cerebral hypo-perfusion condition, and increases the blood flow perfusion in ischemic cerebral tissue.