title: Human myocardial pericytes: multipotent mesodermal precursors exhibiting cardiac specificity.
abstract: Perivascular mesenchymal precursor cells (i.e., pericytes) reside in skeletal muscle where they contribute to myofiber regeneration; however, the existence of similar microvessel-associated regenerative precursor cells in cardiac muscle has not yet been documented. We tested whether microvascular pericytes within human myocardium exhibit phenotypes and multipotency similar to their anatomically and developmentally distinct counterparts. Fetal and adult human heart pericytes (hHPs) express canonical pericyte markers in situ, including CD146, NG2, platelet-derived growth factor receptor (PDGFR) β, PDGFRα, alpha-smooth muscle actin, and smooth muscle myosin heavy chain, but not CD117, CD133, and desmin, nor endothelial cell (EC) markers. hHPs were prospectively purified to homogeneity from ventricular myocardium by flow cytometry, based on a combination of positive- (CD146) and negative-selection (CD34, CD45, CD56, and CD117) cell lineage markers. Purified hHPs expanded in vitro were phenotypically similar to human skeletal muscle-derived pericytes (hSkMPs). hHPs express mesenchymal stem/stromal cell markers in situ and exhibited osteo-, chondro-, and adipogenic potentials but, importantly, no ability for skeletal myogenesis, diverging from pericytes of all other origins. hHPs supported network formation with/without ECs in Matrigel cultures; hHPs further stimulated angiogenic responses under hypoxia, markedly different from hSkMPs. The cardiomyogenic potential of hHPs was examined following 5-azacytidine treatment and neonatal cardiomyocyte coculture in vitro, and intramyocardial transplantation in vivo. Results indicated cardiomyocytic differentiation in a small fraction of hHPs. In conclusion, human myocardial pericytes share certain phenotypic and developmental similarities with their skeletal muscle homologs, yet exhibit different antigenic, myogenic, and angiogenic properties. This is the first example of an anatomical restriction in the developmental potential of pericytes as native mesenchymal stem cells.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pennsylvania, USA; Department of Orthopedic Surgery, University of Pittsburgh, Pennsylvania, USA; Stem Cell Research Centre, University of Pittsburgh, Pennsylvania, USA.
authors.forename: William C W
authors.initials: WC
authors.lastname: Chen
authors.forename: James E
authors.initials: JE
authors.lastname: Baily
authors.forename: Mirko
authors.initials: M
authors.lastname: Corselli
authors.forename: Mary E
authors.initials: ME
authors.lastname: Díaz
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.forename: Guosheng
authors.initials: G
authors.lastname: Xiang
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Gray
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
authors.forename: Bruno
authors.initials: B
authors.lastname: Péault
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009928:Organ Specificity / Q000502:physiology; D020286:Pericytes / Q000166:cytology / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation
keywords: Coronary vessel; Mesenchymal stem cell; Myocardium; Pericyte; Stem cell; Tissue specificity