title: Podocalyxin-like protein 1 is a relevant marker for human c-kit(pos) cardiac stem cells.
abstract: Cardiac progenitor cells (CPCs) from adult myocardium offer an alternative cell therapy approach for ischaemic heart disease. Improved clinical performance of CPCs in clinical trials requires a comprehensive definition of their biology and specific interactions with the environment. In this work we characterize specific human CPC surface markers and study some of their related functions. c-kit(pos) human CPCs (hCPCs) were characterized for cell surface marker expression, pluripotency, early and late cardiac differentiation markers and therapeutic activity in a rat model of acute myocardial infarction. The results indicate that hCPCs are a mesenchymal stem cell (MSC)-like population, with a similar immunoregulatory capacity. A partial hCPC membrane proteome was analysed by liquid chromatography-mass spectrometry/mass spectrometry and 36 proteins were identified. Several, including CD26, myoferlin and podocalyxin-like protein 1 (PODXL), have been previously described in other stem-cell systems. Suppression and overexpression analysis demonstrated that PODXL regulates hCPC activation, migration and differentiation; it also modulates their local immunoregulatory capacity. Therefore, hCPCs are a resident cardiac population that shares many features with hMSCs, including their capacity for local immunoregulation. Expression of PODXL appears to favour the immature state of hCPCs, while its downregulation facilitates their differentiation. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Cardiovascular Development and Repair, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Moscoso
authors.affiliation: Inbiomed Foundation, San Sebastian, Spain.
authors.forename: Naiara
authors.initials: N
authors.lastname: Tejados
authors.affiliation: Vascular Biology and Inflammation Departments, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Barreiro
authors.affiliation: Regenerative Medicine and Heart Transplantation Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Sepúlveda
authors.affiliation: Cardiovascular Development and Repair, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Izarra
authors.affiliation: Cardiovascular Development and Repair, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Calvo
authors.affiliation: Inbiomed Foundation, San Sebastian, Spain.
authors.forename: Akaitz
authors.initials: A
authors.lastname: Dorronsoro
authors.affiliation: Inbiomed Foundation, San Sebastian, Spain.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Salcedo
authors.affiliation: Department of Cardiac Surgery, Hospital de Navarra, Pamplona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Sádaba
authors.affiliation: Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Díez-Juan
authors.affiliation: Inbiomed Foundation, San Sebastian, Spain.
authors.forename: César
authors.initials: C
authors.lastname: Trigueros
authors.affiliation: Cardiovascular Development and Repair, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bernad
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D012795:Sialoglycoproteins / Q000096:biosynthesis*
chemical_list: D000943:Antigens, Differentiation; D012795:Sialoglycoproteins; C001643:podocalyxin; D019009:Proto-Oncogene Proteins c-kit
keywords: Human cardiac progenitor cells; PODXL; differentiation; immunoregulation; membrane proteome; migration