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(Circulation. 2006;114:I-378 – I-383.)
© 2006 American Heart Association, Inc.

Surgery for Aortic and Peripheral Vascular Disease

Development of a New Method for Endovascular Aortic Repair

Combination Therapy of Cell Transplantation and Stent Grafts With a Drug Delivery System

Masaki Kajimoto, MD; Takatsugu Shimono, MD; Koji Hirano, MD; Yoichiro Miyake, MD; Yasuhiro Sawada, MD; Noriyuki Kato, MD; Hitoshi Hirata, MD; Kyoko Imanaka-Yoshida, MD; Masakatsu Nishikawa, MD; Toshimichi Yoshida, MD; Hideto Shimpo, MD; Takashi Horiuchi, PhD; Keiichi Miyamoto, PhD

From the Departments of Thoracic and Cardiovascular Surgery (M.K., T.S., K.H., Y.M., Y.S., H.S.), Orthopaedics (H.H.), Hematology (M.N.), Radiology (N.K.), Pathology (K.I-Y., T.Y.), Mie University School of Medicine, and the Department of Chemistry for Materials (T.H., K.M.), Faculty of Engineering, Mie University, Tsu, Japan

Correspondence to Takatsugu Shimono, MD, Department of Thoracic and Cardiovascular Surgery, Mie University, Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie 514-8507, Japan. E-mail simono-t{at}clin.medic.mie-u.ac.jp

Background— Endovascular aortic repair by stent grafts (S/Gs) has been developed as a less invasive treatment for aortic aneurysms. However, some aneurysmal cavities can remain without organization, causing re-expansion. We demonstrated previously that transplantation of a cell combination (myoblasts and fibroblasts) promoted thrombus organization in a rat model. We also developed basic fibroblast growth factor (bFGF) slow-delivery S/Gs coated with elastin and impregnated with bFGF. Here, we evaluated the effects of cell transplantation combined with bFGF slow release on canine thoracic aortic aneurysmal sacs after S/Gs repair.

Methods and Results— Thoracic aortic aneurysms were surgically created with jugular vein patches in 15 beagles. Myoblasts and fibroblasts of autologous skeletal muscle were isolated and cultured for cell transplantation. The S/Gs had 6 holes and produced endoleaks in the excluded cavities. Collagen gel (gel group, n=5) or a mixture of skeletal myoblasts and fibroblasts with collagen gel (cell group, n=5) were injected into the aneurysmal sacs excluded by the S/Gs. We also studied the effects of combined therapy of bFGF slow-release S/Gs and cell transplantation (hybrid group, n=5). After 14 days, histological analyses revealed that the excluded aneurysmal cavities of the gel group were filled with fresh thrombus, whereas the excluded cavities in the cell-transplanted groups were occupied by organized tissue. The percentages of the organized areas relative to the excluded cavities, evaluated by Masson’s trichrome staining, were 18.1±4.0%, 52.6±4.0%, and 77.1±6.9% in the gel, cell, and hybrid groups, respectively. Collagen fibers had already appeared, and increased numbers of -smooth muscle actin-positive cells were observed in the hybrid group.

Conclusions— Cell transplantation accelerated thrombus organization. Moreover, slow release of bFGF enhanced the effects of cell transplantation. Cell transplantation into unorganized spaces may improve the outcomes of endovascular treatments of aortic aneurysms.

Key Words: aorta • aneurysm • stents • cells • thrombus