title: Human neonatal cardiovascular progenitors: unlocking the secret to regenerative ability.
abstract: Although clinical benefit can be achieved after cardiac transplantation of adult c-kit+ or cardiosphere-derived cells for myocardial repair, these stem cells lack the regenerative capacity unique to neonatal cardiovascular stem cells. Unraveling the molecular basis for this age-related discrepancy in function could potentially transform cardiovascular stem cell transplantation. In this report, clonal populations of human neonatal and adult cardiovascular progenitor cells were isolated and characterized, revealing the existence of a novel subpopulation of endogenous cardiovascular stem cells that persist throughout life and co-express both c-kit and isl1. Epigenetic profiling identified 41 microRNAs whose expression was significantly altered with age in phenotypically-matched clones. These differences were correlated with reduced proliferation and a limited capacity to invade in response to growth factor stimulation, despite high levels of growth factor receptor on progenitors isolated from adults. Further understanding of these differences may provide novel therapeutic targets to enhance cardiovascular regenerative capacity.
authors.affiliation: Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors.forename: Tania I
authors.initials: TI
authors.lastname: Fuentes
authors.forename: Nancy
authors.initials: N
authors.lastname: Appleby
authors.forename: Eric
authors.initials: E
authors.lastname: Tsay
authors.forename: J Julian
authors.initials: JJ
authors.lastname: Martinez
authors.forename: Leonard
authors.initials: L
authors.lastname: Bailey
authors.forename: Nahidh
authors.initials: N
authors.lastname: Hasaniya
authors.forename: Mary
authors.initials: M
authors.lastname: Kearns-Jonker
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000367:Age Factors; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D060850:LIM-Homeodomain Proteins; D035683:MicroRNAs; D017978:Receptors, Growth Factor; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D019009:Proto-Oncogene Proteins c-kit