Copyright © 2005, European Society of Cardiology
Host-derived circulating cells do not significantly contribute to cardiac regeneration in heterotopic rat heart transplants
aDepartment of Biomedical Sciences, University of Padua, Viale G. Colombo 3, 35121 Padova, Italy
bConsiglio Nazionale delle Ricerche Institute of Neurosciences, University of Padua, Italy
cDirezione Sanitaria and Clinica Chirurgica III, Padua General Hospital, Italy
dCORIT (Consorzio per la Ricerca sul Trapianto d'Organi), Italy
eDepartment of Medical and Surgical Sciences, Italy
fInstitute of Pathological Anatomy, University of Padua, Italy
gVenetian Institute of Molecular Medicine (VIMM), Padua, Italy
* Corresponding authors. Ausoni is to be contacted at Department of Biomedical Sciences University of Padua Viale G. Colombo 3, 35121 Padova, Italy. Tel.: +39 049 8276036; fax: +39 049 8276040. Schiaffino, Venetian Institute of Molecular Medicine (VIMM), Via Orus 2, 35129 Padova, Italy. Tel.: +39 049 8276034; fax: +39 049 8276040. Email address: ausoni{at}civ.bio.unipd.it stefano.schiaffino{at}unipd.it
Objectives: The aim of this study was to investigate the contribution of host-derived circulating cells to cardiac repair after tissue damage using the model of heterotopic heart transplantation between transgenic recipient rats expressing green fluorescent protein (GFP) and wild-type donors.
Methods: Unlabeled donor rat hearts, some of which underwent prolonged cold ischemia pretreatment, were transplanted into the abdominal cavity of GFP+ transgenic recipient rats and were analyzed 15 and 90 days after surgery. An additional experimental group underwent heart transplantation following administration of granulocyte-colony stimulatory factor (G-CSF) to mobilize bone marrow cells.
Results: Most transplants contained GFP+ mature cardiomyocytes. However, systematic counting in the transplants showed that the proportion of GFP+ cardiomyocytes was only 0.0005% to 0.008% of all cardiomyocytes. These relative proportions did not change after G-CSF treatment, despite evidence for sustained marrow cell mobilization. Confocal image analysis showed that the majority of GFP+ cardiomyocytes contained a high number of nuclei, suggesting that these cells may derive from fusion events. Very rarely, small GFP+ undifferentiated cells, expressing GATA-4, were also identified. Occasionally, GFP+ endothelial cells, but not smooth muscle cells, were detected in blood vessels of some transplants.
Conclusions: Our results demonstrate that cardiomyocytes expressing a host transgenic marker are detectable in heterotopic heart transplants; however, they do not significantly contribute to repopulation of the damaged myocardium.
KEYWORDS Cardiac regeneration; Adult stem cells; Heterotopic heart transplantation; Trangenic rats
1 These authors contributed equally to the work.
2 These authors contributed equally to the work.
Time for primary review 25 days
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