This Article Full Text Full Text (PDF) All Versions of this Article: 23/12/2266    most recent 01.ATV.0000100403.78731.9Fv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Herder, C. Articles by Seifried, E. Search for Related Content PubMed PubMed Citation Articles by Herder, C. Articles by Seifried, E. Related Collections Gene expression Coagulation Gene therapy

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:2266.)
© 2003 American Heart Association, Inc.

Thrombosis

Sustained Expansion and Transgene Expression of Coagulation Factor VIII–Transduced Cord Blood–Derived Endothelial Progenitor Cells

Christian Herder; Torsten Tonn; Robert Oostendorp; Sven Becker; Ulrich Keller; Christian Peschel; Manuel Grez; Erhard Seifried

From the Institute for Transfusion Medicine and Immunohematology (C.H., T.T., S.B., E.S.), Red Cross Blood Donor Service Baden-Württemberg–Hessen, Frankfurt am Main; Georg-Speyer-Haus (C.H., M.G.), Institute for Biomedical Research, Frankfurt am Main; and III Medizinische Klinik (R.O., U.K., C.P.), Klinikum Rechts der Isar, Technical University Munich, Germany.

Correspondence to Dr Torsten Tonn, Institute for Transfusion Medicine and Immunohematology, Red Cross Blood Donor Service Baden-Württemberg–Hessen, Sandhofstr. 1, 60528 Frankfurt am Main, Germany. E-mail ttonn{at}bsdhessen.de

Objective— Although hemophilia A seems particularly suitable for gene therapy because even low amounts of plasma coagulation factor VIII (FVIII) provide a significant clinical benefit to the patients, the ideal target cell for recombinant FVIII expression and gene therapy approaches remains to be identified. In this study, we tested the capacity of cord blood–derived endothelial progenitor cells (CBECs) for FVIII expression on stable lentiviral transduction.

Methods and Results— CD34⁺ endothelial progenitor cells (EPCs) from cord blood were differentiated into CBECs. Endothelial phenotype was characterized, and lentiviral transduction of early-passage CBECs with a vector encoding FVIII and EGFP did not alter their functional properties and proliferative potential. CBEC could be expanded by 5 to 9 orders of magnitude, thus allowing the expansion of up to 10¹⁵ FVIII-secreting CBECs, starting from as little as 10⁶ CD34⁺ cells. CBECs proved to be highly suitable for FVIII secretion, with 0.35 to 0.39 IU FVIII:C/5x10⁴ cells per 48 hours (7.0 to 7.8 IU FVIII:C/10⁶ cells per 48 hours), which remained stable over the expansion period.

Conclusions— Our data indicate that CBECs are attractive target cells for inherited coagulation disorders such as hemophilia A, which on lentiviral transduction can be readily expanded to large numbers of transplantable gene-modified cells in vitro.

Key Words: hemophilia • factor VIII • cord blood • endothelial progenitor cells • lentiviral gene therapy

This article has been cited by other articles:

				T. Higuchi, M. Anton, K. Dumler, S. Seidl, J. Pelisek, A. Saraste, A. Welling, F. Hofmann, R. A.J. Oostendorp, B. Gansbacher, et al. Combined Reporter Gene PET and Iron Oxide MRI for Monitoring Survival and Localization of Transplanted Cells in the Rat Heart J. Nucl. Med., July 1, 2009; 50(7): 1088 - 1094. [Abstract] [Full Text] [PDF]

				M. van den Biggelaar, E. A.M. Bouwens, N. A. Kootstra, R. P. Hebbel, J. Voorberg, and K. Mertens Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells Haematologica, May 1, 2009; 94(5): 670 - 678. [Abstract] [Full Text] [PDF]

				S. F. De Meyer, K. Vanhoorelbeke, M. K. Chuah, I. Pareyn, V. Gillijns, R. P. Hebbel, D. Collen, H. Deckmyn, and T. VandenDriessche Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral vectors expressing von Willebrand factor Blood, June 15, 2006; 107(12): 4728 - 4736. [Abstract] [Full Text] [PDF]

				L. G. Melo, M. Gnecchi, A. S. Pachori, D. Kong, K. Wang, X. Liu, R. E. Pratt, and V. J. Dzau Endothelium-Targeted Gene and Cell-Based Therapies for Cardiovascular Disease Arterioscler Thromb Vasc Biol, October 1, 2004; 24(10): 1761 - 1774. [Abstract] [Full Text] [PDF]

				J. D. Pearson Using Endothelial Progenitor Cells for Gene Therapy Arterioscler Thromb Vasc Biol, December 1, 2003; 23(12): 2117 - 2118. [Full Text] [PDF]