Plasticity of CD133+ cells: role in pulmonary vascular remodeling.
OBJECTIVE
Studies in pulmonary arteries (PA) of patients with chronic obstructive pulmonary disease (COPD) suggest that bone marrow-derived endothelial progenitor cells (CD133(+)) may infiltrate the intima and differentiate into smooth muscle cells (SMC). This study aimed to evaluate the plasticity of CD133(+) cells to differentiate into SMC and endothelial cells (EC) in both cell culture and human isolated PA.


METHODS
Plasticity of granulocyte-colony stimulator factor (G-CSF)-mobilized peripheral blood CD133(+) cells was assessed in co-cultures with primary lines of human PA endothelial cells (PAEC) or SMC (PASMC) and in isolated human PA. We also evaluated if the phenotype of differentiated progenitor cells was acquired by fusion or differentiation.


RESULTS
The in vitro studies demonstrated CD133(+) cells may acquire the morphology and phenotype of the cells they were co-cultured with. CD133(+) cells co-incubated with human isolated PA were able to migrate into the intima and differentiate into SMC. Progenitor cell differentiation was produced without fusion with mature cells.


CONCLUSIONS
We provide evidence of plasticity of CD133(+) cells to differentiate into both endothelial cells and SMC, reinforcing the idea of their potential role in the remodeling process of PA in COPD. This process was conducted by transdifferentiation and not by cell fusion.
Díez
Marta
M
Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Ciber de Enfermedades Respiratorias, Universitat de Barcelona, Barcelona, Spain.
Barberà
Joan A
JA
Ferrer
Elisabet
E
Fernández-Lloris
Raquel
R
Pizarro
Sandra
S
Roca
Josep
J
Peinado
Victor I
VI
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology; D010455:Peptides / Q000378:metabolism*; D010641:Phenotype; D011651:Pulmonary Artery / Q000166:cytology* / Q000502:physiology; D017539:Tunica Intima / Q000166:cytology
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides