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(Circulation. 2005;112:I-111 – I-116.)
© 2005 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Method of Cell Transplantation Promoting the Organization of Intraarterial Thrombus

Koji Hirano, MD; Takatsugu Shimono, MD; Kyoko Imanaka-Yoshida, MD; Keiichi Miyamoto, PhD; Kazuya Fujinaga, MD; Masaki Kajimoto, MD; Yoichiro Miyake, MD; Masakatsu Nishikawa, MD; Toshimichi Yoshida, MD; Atsumasa Uchida, MD; Hideto Shimpo, MD; Isao Yada, MD; Hitoshi Hirata, MD

From the Departments of Thoracic and Cardiovascular Surgery (K.H., T.S., K.F., M.K., Y.M., H.S.), Orthopaedics (H.H., A.U.), Hematology (M.N.), and Pathology (K.I.-Y., T.Y.), Mie University School of Medicine, Tsu; the Department of Chemistry for Materials (K.M.), Faculty of Engineering, Mie University, Tsu; and Graduate School of Health Science (I.Y.), Suzuka University of Medical Science, Suzuka, Japan.

Correspondence to Takatsugu Shimono, MD, Department of Thoracic and Cardiovascular Surgery, Mie University School of Medicine, 2-172, Edobashi, Tsu, Mie 514-8507, Japan. E-mail simono-t{at}clin.medic.mie-u.ac.jp

Background— Endovascular aortic repairs have been developed as less invasive treatments for aortic aneurysms. Some aneurismal cavities, however, remain without organization, causing a re-expansion of the aneurysms. We studied cell transplantation into the aneurismal sac to promote the organization of thrombus for the complete healing of aneurysms.

Methods and Results— Skin fibroblasts and skeletal myoblasts were isolated from rats for cell transplantation. An intraarterial thrombus model was made by ligation of the carotid artery. Culture medium (medium group, n=11), collagen gel (gel group, n=11), fibroblasts with collagen gel (F group, n=15), myoblasts with collagen gel (M group, n=12), or mixture of fibroblasts and myoblasts with collagen gel (F+M group, n=14) were injected into the thrombus. After 28 days, histologically, the arterial lumens of the F and M groups were partly filled with fibrous tissues, whereas in the F+M group organization was almost completed and luminal sizes diminished. Immunohistochemical staining demonstrated that -smooth muscle actin-positive cells were more abundantly contained in the organized area of the F+M group than in the other groups. We also analyzed cellular function in vitro with immunofluorescence; coculture of fibroblasts and myoblasts showed that the fraction of -smooth muscle actin-positive fibroblasts increased. This phenomenon accounts for the rapid organization of thrombus in the F+M group in vivo.

Conclusions— Cell transplantation accelerated thrombus organization. Especially, myoblasts enhanced differentiation of fibroblasts into myofibroblasts, contributing to rapid thrombus organization. Cell transplantation into unorganized spaces seems applicable to endovascular treatment of aneurysms.

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