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MEDICAL SCIENCES
Tissue-engineered endothelial and epithelial implants differentially and synergistically regulate airway repair

Brett G. Zani^*,, Koji Kojima, Charles A. Vacanti, and Elazer R. Edelman^*,

*Harvard–Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139; and Laboratory for Tissue Engineering and Regenerative Medicine, Department of Anesthesiology, and Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115

Communicated by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, March 12, 2008 (received for review December 27, 2007)

Abstract

The trilaminate vascular architecture provides biochemical regulation and mechanical integrity. Yet regulatory control can be regained after injury without recapitulating tertiary structure. Tissue-engineered (TE) endothelium controls repair even when placed in the perivascular space of injured vessels. It remains unclear from vascular repair studies whether endothelial implants recapitulate the vascular epithelial lining or expose injured tissues to endothelial cells (ECs) with unique healing potential because ECs line the vascular epithelium and the vasa vasorum. We examined this issue in a nonvascular tubular system, asking whether airway repair is controlled by bronchial epithelial cells (EPs) or by ECs of the perfusing bronchial vasculature. Localized bronchial denuding injury damaged epithelium, narrowed bronchial lumen, and led to mesenchymal cell hyperplasia, hypervascularity, and inflammatory cell infiltration. Peribronchial TE constructs embedded with EPs or ECs limited airway injury, although optimum repair was obtained when both cells were present in TE matrices. EC and EP expression of PGE₂, TGFβ1, TGFβ2, GM-CSF, IL-8, MCP-1, and soluble VCAM-1 and ICAM-1 was altered by matrix embedding, but expression was altered most significantly when both cells were present simultaneously. EPs may provide for functional control of organ injury and fibrous response, and ECs may provide for preservation of tissue perfusion and the epithelium in particular. Together the two cells optimize functional restoration and healing, suggesting that multiple cells of a tissue contribute to the differentiated biochemical function and repair of a tissue, but need not assume a fixed, ordered architectural relationship, as in intact tissues, to achieve these effects.

tissue engineering | airway disease | vascular disease

Author contributions: B.G.Z., K.K., C.A.V., and E.R.E. designed research; B.G.Z. and K.K. performed research; C.A.V. and E.R.E. contributed new reagents/analytic tools; B.G.Z., K.K., and E.R.E. analyzed data; and B.G.Z. and E.R.E. wrote the paper.

Conflict of interest statement: The authors have a pending patent on the technology presented in this article that has been licensed to Pervasis Therapeutics. R.L. and E.R.E. hold an equity share in this company.

To whom correspondence should be addressed. E-mail: zani{at}mit.edu

© 2008 by The National Academy of Sciences of the USA

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