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(Circulation. 2006;114:I-138 – I-144.)
© 2006 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Tissue-Engineered Injectable Collagen-Based Matrices for Improved Cell Delivery and Vascularization of Ischemic Tissue Using CD133⁺ Progenitors Expanded From the Peripheral Blood

Erik J. Suuronen, PhD; John P. Veinot, MD; Serena Wong, BSc; Varun Kapila, BSc; Joel Price, MD; May Griffith, PhD; Thierry G. Mesana, MD, PhD; Marc Ruel, MD, MPH

From the Division of Cardiac Surgery (E.J.S., V.K., J.P., T.G.M., M.R.), the Department of Cellular and Molecular Medicine (S.W., M.G., M.R.), and the Department of Pathology and Laboratory Medicine (J.P.V.), University of Ottawa, Ottawa, Ontario, Canada.

Correspondence to Marc Ruel, University of Ottawa Heart Institute, Division of Cardiac Surgery, 40 Ruskin St, Laboratory H553, Ottawa, Ontario, Canada, K1Y 4W7. E-mail mruel{at}ottawaheart.ca

Background— The use of stem and/or progenitor cells to achieve potent vasculogenesis in humans has been hindered by low cell numbers, implant capacity, and survival. This study investigated the expansion of CD133⁺ cells and the use of an injectable collagen-based tissue engineered matrix to support cell delivery and implantation within target ischemic tissue.

Methods and Results— Adult human CD133⁺ progenitor cells from the peripheral blood were generated and expanded by successive removal and culture of CD133^– cell fractions, and delivered within an injectable collagen-based matrix into the ischemic hindlimb of athymic rats. Controls received injections of phosphate-buffered saline, matrix, or CD133⁺ cells alone. Immunohistochemistry of hindlimb muscle 2 weeks after treatment revealed that the number of CD133⁺ cells retained within the target site was >2-fold greater when delivered by matrix than when delivered alone (P<0.01). The transplanted CD133⁺ cells incorporated into vascular structures, and the matrix itself also was vascularized. Rats that received matrix and CD133⁺ cells demonstrated greater intramuscular arteriole and capillary density than other treatment groups (P<0.05 and P<0.01, respectively).

Conclusions— Compared with other experimental approaches, treatment of ischemic muscle tissue with generated CD133⁺ progenitor cells delivered in an injectable collagen-based matrix significantly improved the restoration of a vascular network. This work demonstrates a novel approach for the expansion and delivery of blood CD133⁺ cells with resultant improvement of their implantation and vasculogenic capacity.

Key Words: angiogenesis • cells • endothelial progenitor cells • ischemia • revascularization • tissue engineering