This Article Full Text Full Text (PDF) All Versions of this Article: 35/10/2378    most recent 01.STR.0000141893.33677.5dv1 Alert me when this article is cited 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 He, T. Articles by Katusic, Z. S. Search for Related Content PubMed PubMed Citation Articles by He, T. Articles by Katusic, Z. S. Related Collections Endothelium/vascular type/nitric oxide Angiogenesis Cell biology/structural biology

(Stroke. 2004;35:2378.)
© 2004 American Heart Association, Inc.

Original Contributions

Transplantation of Circulating Endothelial Progenitor Cells Restores Endothelial Function of Denuded Rabbit Carotid Arteries

Tongrong He, MD PhD; Leslie A. Smith; Sean Harrington, BS; Karl A. Nath, MD; Noel M. Caplice, MD PhD Zvonimir S. Katusic, MD PhD

From the Mayo Clinic of Medicine, Rochester, Minn.

Background and Purpose— Circulating endothelial progenitor cells (EPCs) play an important role in repair of injured vascular endothelium and neovascularization. The present study was designed to determine the effect of EPCs transplantation on the regeneration of endothelium and recovery of endothelial function in denuded carotid arteries.

Methods— Isolated mononuclear cells from rabbit peripheral blood were cultured in endothelial growth medium for 7 days, yielding EPCs. A rabbit model of common carotid artery denudation by passage of a deflated balloon catheter was used to evaluate the effects of EPCs on endothelial regeneration and vasomotor function. Immediately after denudation, autologous EPCs (10⁵ cells in 200 µL saline) or 200 µL saline alone (control) were administered into the lumen of injured artery.

Results— Four weeks after transplantation, fluorescence-labeled colonies of EPCs were found in the vessel wall. Local transplantation of EPCs as compared with saline administration accelerated endothelialization and significantly improved endothelium-dependent relaxation when assessed 4 weeks after denudation (n=4 to 5, P<0.05). Transplantation of EPCs did not affect vasomotor function of arterial smooth muscle cells. Protein array analysis of conditioned media obtained from cultured EPCs demonstrated the ability of these cells to produce and release a number of proangiogenic cytokines.

Conclusions— We conclude that local delivery of cultured circulating EPCs into the lumen of denuded carotid arteries accelerates endothelialization and improves endothelial function. Paracrine effects of EPCs may contribute to regenerative properties of EPCs.

Key Words: angiogenesis • carotid arteries • cell culture • cell transplantation • nitric oxide • stem cells

This article has been cited by other articles:

				C.-F. Lam, P.-J. Chang, Y.-S. Huang, Y.-H. Sung, C.-C. Huang, M.-W. Lin, Y.-C. Liu, and Y.-C. Tsai Prolonged Use of High-Dose Morphine Impairs Angiogenesis and Mobilization of Endothelial Progenitor Cells in Mice Anesth. Analg., August 1, 2008; 107(2): 686 - 692. [Abstract] [Full Text] [PDF]

				T. He, T. Lu, L. V. d'Uscio, C.-F. Lam, H.-C. Lee, and Z. S. Katusic Angiogenic Function of Prostacyclin Biosynthesis in Human Endothelial Progenitor Cells Circ. Res., July 3, 2008; 103(1): 80 - 88. [Abstract] [Full Text] [PDF]

				S. Brunner, H. D. Theiss, A. Murr, T. Negele, and W.-M. Franz Primary hyperparathyroidism is associated with increased circulating bone marrow-derived progenitor cells Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1670 - E1675. [Abstract] [Full Text] [PDF]

				K. Lamping Endothelial Progenitor Cells: Sowing the Seeds for Vascular Repair Circ. Res., May 11, 2007; 100(9): 1243 - 1245. [Full Text] [PDF]

				A. V. R. Santhanam, L. A. Smith, T. He, K. A. Nath, and Z. S. Katusic Endothelial Progenitor Cells Stimulate Cerebrovascular Production of Prostacyclin By Paracrine Activation of Cyclooxygenase-2 Circ. Res., May 11, 2007; 100(9): 1379 - 1388. [Abstract] [Full Text] [PDF]

				S. V. Pislaru, A. Harbuzariu, R. Gulati, T. Witt, N. P. Sandhu, R. D. Simari, and G. S. Sandhu Magnetically Targeted Endothelial Cell Localization in Stented Vessels J. Am. Coll. Cardiol., November 7, 2006; 48(9): 1839 - 1845. [Abstract] [Full Text] [PDF]

				R. Gulati and R. D. Simari Cell Therapy for Angiogenesis: Embracing Diversity Circulation, September 13, 2005; 112(11): 1522 - 1524. [Full Text] [PDF]

				T. He, T. E. Peterson, and Z. S. Katusic Paracrine mitogenic effect of human endothelial progenitor cells: role of interleukin-8 Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H968 - H972. [Abstract] [Full Text] [PDF]

				V. J. Dzau, M. Gnecchi, A. S. Pachori, F. Morello, and L. G. Melo Therapeutic Potential of Endothelial Progenitor Cells in Cardiovascular Diseases Hypertension, July 1, 2005; 46(1): 7 - 18. [Abstract] [Full Text] [PDF]