Tissue-Specific Stem Cells

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Toward Engineering a Human Neoendothelium with Circulating Progenitor Cells†‡§

  1. Josephine B. Allen,
  2. Sadiya Khan,
  3. Karen A. Lapidos,
  4. Guillermo A. Ameer¶,*

Article first published online: 9 DEC 2009

DOI: 10.1002/stem.275

Issue

STEM CELLS

STEM CELLS

Volume 28, Issue 2, pages 318–328, February 2010

Additional Information

How to Cite

Allen, J. B., Khan, S., Lapidos, K. A. and Ameer, G. A. (2010), Toward Engineering a Human Neoendothelium with Circulating Progenitor Cells. STEM CELLS, 28: 318–328. doi: 10.1002/stem.275

Author Information

  1. Northwestern University, Evanston, Illinois, USA

  1. Telephone: 847-467-6719; Fax: 847-491-4928

*Northwestern University, Biomedical Engineering Department, 2145 Sheridan Road, E310, Evanston, Illinois 60208, USA, and Department of Surgery, Feinberg School of Medicine, Chicago, Illinois 60611, USA

  1. †

    Author contributions: J.A.: Conception and design, collection and analysis of data, manuscript writing; S.K. and K.L.: Collection and analysis of data; G.A.: Conception and design, manuscript writing, final approval of manuscript. G.A. is a member of the Institute for BioNanotechnology in Medicine.

  2. ‡

    Disclosure of potential conflicts of interest is found at the end of this article.

  3. §

    First published online in STEM CELLSEXPRESS January 28, 2010.

Publication History

  1. Issue published online: 16 FEB 2010
  2. Article first published online: 9 DEC 2009
  3. Accepted manuscript online: 9 DEC 2009 12:00AM EST
  4. Manuscript Accepted: 24 NOV 2009
  5. Manuscript Received: 14 JUL 2009

Funded by

  • Illinois Regenerative Medicine Institute and the Department of Defense (TATRC). Grant Number: W81XWH-05-1-0381
  • American Heart Association pre-doctoral fellowship

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Keywords:

  • Endothelial progenitor cells;
  • Elastomer;
  • Antithrombogenic;
  • Fibrolytic

Abstract

Tissue-engineered vascular grafts may one day provide a solution to many of the limitations associated with using synthetic vascular grafts. However, identifying a suitable cell source and polymer scaffold to recreate the properties of a native blood vessel remains a challenge. In this work, we assess the feasibility of using endothelial progenitor cells (EPCs) found in circulating blood to generate a functional endothelium on poly(1,8-octanediol-co-citrate) (POC), a biodegradable elastomeric polyester. EPCs were isolated from human blood and biochemically differentiated into endothelial-like cells (HE-like) in vitro. The differentiated cell phenotype and function was confirmed by the appearance of the characteristic endothelial cell (EC) cobblestone morphology and positive staining for EC markers, von Willebrand factor, vascular endothelial cadherin, flk-1, and CD31. In addition, HE-like cells cultured on POC express endothelial nitric oxide synthase at levels comparable to aortic ECs. Furthermore, as with mature endothelial cells, HE-like cell populations show negligible expression of tissue factor. Similarly, HE-like cells produce and secrete prostacyclin and tissue plasminogen activator at levels comparable to venous and aortic ECs. When compared to fibroblast cells, HE-like cells cultured on POC show a decrease in the rate of plasma and whole-blood clot formation as well as a decrease in platelet adhesion. Finally, the data show that HE-like cells can withstand physiological shear stress of 10 dynes/cm2 when cultured on POC-modified expanded poly(tetrafluoroethylene) vascular grafts. Collectively, these data are the foundation for future clinical studies in the creation of an autologous endothelial cell-seeded vascular graft. STEM CELLS 2010;28:318–328

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