Progenitor cells from the explanted heart generate immunocompatible myocardium within the transplanted donor heart.
BACKGROUND
Chronic rejection, accelerated coronary atherosclerosis, myocardial infarction, and ischemic heart failure determine the unfavorable evolution of the transplanted heart in humans.


OBJECTIVE
Here we tested whether the pathological manifestations of the transplanted heart can be corrected partly by a strategy that implements the use of cardiac progenitor cells from the recipient to repopulate the donor heart with immunocompatible cardiomyocytes and coronary vessels.


RESULTS
A large number of cardiomyocytes and coronary vessels were created in a rather short period of time from the delivery, engraftment, and differentiation of cardiac progenitor cells from the recipient. A proportion of newly formed cardiomyocytes acquired adult characteristics and was integrated structurally and functionally within the transplant. Similarly, the regenerated arteries, arterioles, and capillaries were operative and contributed to the oxygenation of the chimeric myocardium. Attenuation in the extent of acute damage by repopulating cardiomyocytes and vessels decreased significantly the magnitude of myocardial scarring preserving partly the integrity of the donor heart.


CONCLUSIONS
Our data suggest that tissue regeneration by differentiation of recipient cardiac progenitor cells restored a significant portion of the rejected donor myocardium. Ultimately, immunosuppressive therapy may be only partially required improving quality of life and lifespan of patients with cardiac transplantation.
D'Alessandro
David A
DA
Department of Cardiothoracic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, New York, USA.
Kajstura
Jan
J
Hosoda
Toru
T
Gatti
Alessandro
A
Bello
Ricardo
R
Mosna
Federico
F
Bardelli
Silvana
S
Zheng
Hanqiao
H
D'Amario
Domenico
D
Padin-Iruegas
M Elena
ME
Carvalho
Adriana Bastos
AB
Rota
Marcello
M
Zembala
Michael O
MO
Stern
David
D
Rimoldi
Ornella
O
Urbanek
Konrad
K
Michler
Robert E
RE
Leri
Annarosa
A
Anversa
Piero
P
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D002459:Cell Fusion; D003331:Coronary Vessels / Q000166:cytology; D004285:Dogs; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006333:Heart Failure / Q000276:immunology / Q000473:pathology; D016027:Heart Transplantation; D006648:Histocompatibility; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology*; D012038:Regeneration / Q000276:immunology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
D007166:Immunosuppressive Agents; D049452:Green Fluorescent Proteins