Characterization of CD133 Antibody-Directed Recellularized Heart Valves.
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.
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA. kwilliam@wakehealth.edu.
J Koudy
JK
Williams
Department of Cardiothoracic Surgery, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
Elizabeth S
ES
Miller
Department of Cardiothoracic Surgery, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
Magan R
MR
Lane
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
Anthony
A
Atala
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
James J
JJ
Yoo
Department of Cardiothoracic Surgery, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
James E
JE
Jordan
D000071916:AC133 Antigen; D000199:Actins / Q000032:analysis; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D057005:Bioengineering / Q000379:methods*; D001705:Bioprosthesis; D004452:Echocardiography; D006023:Glycoproteins / Q000276:immunology*; D006350:Heart Valve Prosthesis; D007150:Immunohistochemistry; D010455:Peptides / Q000276:immunology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology; D011474:Prosthesis Design; D012756:Sheep; D013552:Swine; D054457:Tissue Scaffolds; D020858:Tissue and Organ Harvesting / Q000379:methods; D014746:Vimentin / Q000032:analysis; D060509:Wnt3A Protein / Q000032:analysis; D051176:beta Catenin / Q000032:analysis
D000071916:AC133 Antigen; D000199:Actins; D000906:Antibodies; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014746:Vimentin; D060509:Wnt3A Protein; D051176:beta Catenin
CD133; Cell signaling; Endothelial precursor cells; Matrix; Remodeling; Sheep; Transdifferentiation; Valve interstitial cells