Characterization of CD133 Antibody-Directed Recellularized Heart Valves

J. Koudy Williams, Elizabeth S. Miller, Magan R. Lane, Anthony Atala, James J. Yoo, James E. Jordan

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

CD133mAb conjugation (CD133-C) hastens in vivo recellularization of decellularized porcine heart valve scaffolds when placed in the pulmonary position of sheep. We now characterize this early cellularization process 4 h, 3, 7, 14, 30, or 90 days post-implantation. Quantitative immunohistochemistry identified cell types as well as changes in cell markers and developmental cues. CD133+/CD31 cells adhered to the leaflet surface of CD133-C leaflets by 3 days and transitioned to native leaflet-like CD133/CD31+ cells by 30 days. Leaflet interstitium became increasingly populated with both alpha-smooth muscle actin (αSMA) and vimentin+ cells from 14 to 90 days post-implantation. Wnt3a, and beta-catenin proteins were expressed at early (3–14 days) but not later (30–90 days) time points. In contrast, matrix metalloproteinase-2 and periostin proteins were increasingly expressed over 90 days. Thus, early development of CD133-C constructs includes a fairly rapid transition from a precursor cell adhesion/migration/transdifferentiation phenotype to a more mature cell/native valve-like matrix metabolism phenotype.

Original languageEnglish (US)
Pages (from-to)411-420
Number of pages10
JournalJournal of cardiovascular translational research
Volume8
Issue number7
DOIs
StatePublished - Sep 4 2015
Externally publishedYes

Keywords

  • CD133
  • Cell signaling
  • Endothelial precursor cells
  • Matrix
  • Remodeling
  • Sheep
  • Transdifferentiation
  • Valve interstitial cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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