Tissue-engineered vascular grafts form neovessels that arise from regeneration of the adjacent blood vessel

Narutoshi Hibino, Gustavo Villalona, Nicholas Pietris, Daniel R. Duncan, Adam Schoffner, Jason D. Roh, Tai Yi, Lawrence W. Dobrucki, Dane Mejias, Rajendra Sawh-Martinez, Jamie K. Harrington, Albert Sinusas, Diane S. Krause, Themis Kyriakides, W. Mark Saltzman, Jordan S. Pober, Toshiharu Shin'oka, Christopher K. Breuer

Research output: Contribution to journalArticle

Abstract

We developed a tissue-engineered vascular graft composed of biodegradable scaffold seeded with autologous bone marrow-derived mononuclear cells (BMMCs) that is currently in clinical trial and developed analogous mouse models to study mechanisms of neovessel formation. We previously reported that seeded human BMMCs were rapidly lost after implantation into immunodeficient mice as host macrophages invaded the graft. As a consequence, the resulting neovessel was entirely of host cell origin. Here, we investigate the source of neotissue cells in syngeneic BMMC-seeded grafts, implanted into immunocompetent mouse recipients. We again find that seeded BMMCs are lost, declining to 0.02% at 14 d, concomitant with host macrophage invasion. In addition, we demonstrate using sex-mismatched chimeric hosts that bone marrow is not a significant source of endothelial or smooth muscle cells that comprise the neovessel. Furthermore, using composite grafts formed from seeded scaffold anastomosed to sex-mismatched natural vessel segments, we demonstrate that the adjacent vessel wall is the principal source of these endothelial and smooth muscle cells, forming 93% of proximal neotissue. These findings have important implications regarding fundamental mechanisms underlying neotissue formation; in this setting, the tissue-engineered construct functions by mobilizing the body's innate healing capabilities to "regenerate" neotissue from preexisting committed tissue cells.

Original languageEnglish (US)
Pages (from-to)2731-2739
Number of pages9
JournalFASEB Journal
Volume25
Issue number8
DOIs
StatePublished - Aug 2011
Externally publishedYes

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Keywords

  • Bone marrow chimera
  • Composite vascular implant
  • Microcomputed tomography angiography

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Hibino, N., Villalona, G., Pietris, N., Duncan, D. R., Schoffner, A., Roh, J. D., Yi, T., Dobrucki, L. W., Mejias, D., Sawh-Martinez, R., Harrington, J. K., Sinusas, A., Krause, D. S., Kyriakides, T., Saltzman, W. M., Pober, J. S., Shin'oka, T., & Breuer, C. K. (2011). Tissue-engineered vascular grafts form neovessels that arise from regeneration of the adjacent blood vessel. FASEB Journal, 25(8), 2731-2739. https://doi.org/10.1096/fj.11-182246