PMID- 17965233
OWN - NLM
STAT- MEDLINE
DCOM- 20080128
LR  - 20220310
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 104
IP  - 45
DP  - 2007 Nov 6
TI  - Bone marrow cells adopt the cardiomyogenic fate in vivo.
PG  - 17783-8
AB  - 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.
FAU - Rota, Marcello
AU  - Rota M
AD  - Cardiovascular Research Institute, Department of Medicine, New York Medical 
      College, Valhalla, NY 10595, USA.
FAU - Kajstura, Jan
AU  - Kajstura J
FAU - Hosoda, Toru
AU  - Hosoda T
FAU - Bearzi, Claudia
AU  - Bearzi C
FAU - Vitale, Serena
AU  - Vitale S
FAU - Esposito, Grazia
AU  - Esposito G
FAU - Iaffaldano, Grazia
AU  - Iaffaldano G
FAU - Padin-Iruegas, M Elena
AU  - Padin-Iruegas ME
FAU - Gonzalez, Arantxa
AU  - Gonzalez A
FAU - Rizzi, Roberto
AU  - Rizzi R
FAU - Small, Narissa
AU  - Small N
FAU - Muraski, John
AU  - Muraski J
FAU - Alvarez, Roberto
AU  - Alvarez R
FAU - Chen, Xiongwen
AU  - Chen X
FAU - Urbanek, Konrad
AU  - Urbanek K
FAU - Bolli, Roberto
AU  - Bolli R
FAU - Houser, Steven R
AU  - Houser SR
FAU - Leri, Annarosa
AU  - Leri A
FAU - Sussman, Mark A
AU  - Sussman MA
FAU - Anversa, Piero
AU  - Anversa P
LA  - eng
GR  - R01 HL088243/HL/NHLBI NIH HHS/United States
GR  - R01 HL088243-01/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20071026
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antigens, CD)
RN  - 9007-49-2 (DNA)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
SB  - IM
MH  - Antigens, CD/analysis
MH  - Bone Marrow Cells/*cytology
MH  - Cell Differentiation/*physiology
MH  - Cell Division
MH  - DNA/genetics
MH  - Diploidy
MH  - Humans
MH  - Leukocyte Common Antigens/analysis
MH  - Myocardial Infarction/therapy
MH  - Myocytes, Cardiac/*cytology/physiology
MH  - Regeneration
MH  - *Stem Cell Transplantation
MH  - Tissue Donors
PMC - PMC2077031
COIS- The authors declare no conflict of interest.
EDAT- 2007/10/30 09:00
MHDA- 2008/01/29 09:00
PMCR- 2008/05/06
CRDT- 2007/10/30 09:00
PHST- 2007/10/30 09:00 [pubmed]
PHST- 2008/01/29 09:00 [medline]
PHST- 2007/10/30 09:00 [entrez]
PHST- 2008/05/06 00:00 [pmc-release]
AID - 0706406104 [pii]
AID - 8004 [pii]
AID - 10.1073/pnas.0706406104 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17783-8. doi: 
      10.1073/pnas.0706406104. Epub 2007 Oct 26.