title: Bone marrow cells adopt the cardiomyogenic fate in vivo.
abstract: The possibility that adult bone marrow cells (BMCs) retain a remarkable degree of developmental plasticity and acquire the cardiomyocyte lineage after infarction has been challenged, and the notion of BMC transdifferentiation has been questioned. The center of the controversy is the lack of unequivocal evidence in favor of myocardial regeneration by the injection of BMCs in the infarcted heart. Because of the interest in cell-based therapy for heart failure, several approaches including gene reporter assay, genetic tagging, cell genotyping, PCR-based detection of donor genes, and direct immunofluorescence with quantum dots were used to prove or disprove BMC transdifferentiation. Our results indicate that BMCs engraft, survive, and grow within the spared myocardium after infarction by forming junctional complexes with resident myocytes. BMCs and myocytes express at their interface connexin 43 and N-cadherin, and this interaction may be critical for BMCs to adopt the cardiomyogenic fate. With time, a large number of myocytes and coronary vessels are generated. Myocytes show a diploid DNA content and carry, at most, two sex chromosomes. Old and new myocytes show synchronicity in calcium transients, providing strong evidence in favor of the functional coupling of these two cell populations. Thus, BMCs transdifferentiate and acquire the cardiomyogenic and vascular phenotypes restoring the infarcted heart. Together, our studies reveal that locally delivered BMCs generate de novo myocardium composed of integrated cardiomyocytes and coronary vessels. This process occurs independently of cell fusion and ameliorates structurally and functionally the outcome of the heart after infarction.
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Marcello
authors.initials: M
authors.lastname: Rota
authors.forename: Jan
authors.initials: J
authors.lastname: Kajstura
authors.forename: Toru
authors.initials: T
authors.lastname: Hosoda
authors.forename: Claudia
authors.initials: C
authors.lastname: Bearzi
authors.forename: Serena
authors.initials: S
authors.lastname: Vitale
authors.forename: Grazia
authors.initials: G
authors.lastname: Esposito
authors.forename: Grazia
authors.initials: G
authors.lastname: Iaffaldano
authors.forename: M Elena
authors.initials: ME
authors.lastname: Padin-Iruegas
authors.forename: Arantxa
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Roberto
authors.initials: R
authors.lastname: Rizzi
authors.forename: Narissa
authors.initials: N
authors.lastname: Small
authors.forename: John
authors.initials: J
authors.lastname: Muraski
authors.forename: Roberto
authors.initials: R
authors.lastname: Alvarez
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Chen
authors.forename: Konrad
authors.initials: K
authors.lastname: Urbanek
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
authors.forename: Steven R
authors.initials: SR
authors.lastname: Houser
authors.forename: Annarosa
authors.initials: A
authors.lastname: Leri
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sussman
authors.forename: Piero
authors.initials: P
authors.lastname: Anversa
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division; D004247:DNA / Q000235:genetics; D004171:Diploidy; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D009203:Myocardial Infarction / Q000628:therapy; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology; D012038:Regeneration; D033581:Stem Cell Transplantation; D014019:Tissue Donors
chemical_list: D015703:Antigens, CD; D004247:DNA; D017493:Leukocyte Common Antigens