Volume 44, February 2004 TRANSFUSION 239 Blackwell Science, LtdOxford, UKTRFTransfusion0041-11322004 American Association of Blood BanksFebruary 2004442Original Article MARROW CELLS AFTER HEART INJURYCIULLA ET AL. ABBREVIATIONS: LV = left ventricle; MMNCs = marrow MNCs. From the Istituto di Medicina Cardiovascolare, Centro di Fisiologia Clinica e Ipertensione, University of Milan, IRCCS Ospedale Maggiore di Milano; II Cattedra di Anatomia Patologica, Dipartimento Medicina, Chirurgia e Odontoiatria, University of Milan, A. O. San Paolo and IRCCS Ospedale Maggiore di Milano; Cell Factory “Franco Calori,” Centro Trasfusionale e di Immunologia dei Trapianti, IRCCS Ospedale Maggiore di Milano, Milan, Italy. Address reprint requests to: Michele M. Ciulla, MD, PhD, Istituto di Medicina Cardiovascolare, Centro di Fisiologia Clinica e Ipertensione, Università di Milano, IRCCS Ospedale Maggiore di Milano, Via F. Sforza 35–20122 Milano, Italy; e-mail: michele.ciulla@unimi.it. This work was supported by grants from Cariplo, Eurocord II, Eurocord III, Progetto Ricerca Finalizzata 2001, and FIRB 2001. Received for publication August 1, 2003; revision received September 9, 2003, and accepted September 16, 2003. TRANSFUSION 2004;44:239-244. T R A N S P L A N T A T I O N A N D C E L L U L A R E N G I N E E R I N G The translocation of marrow MNCs after experimental myoca cryoinjury is proportional to the infarcted area Michele M. Ciulla, Stefano Ferrero, Lorenza Lazzari, Raffaella Pacchiana, Roberta Paliotti, Umberto Gianelli, Giuseppe Busca, Arturo Esposito, Silvano Bosari, Fabio Magrini, and Paolo Rebull BACKGROUND: The selective homing of peripherally injected marrow MNCs (MMNCs) has recently been demonstrated in a model of cryodamaged heart. However, the mechanism underlying this phenomenon is still unknown. In the hypothesis that this process is related to the necrotic area extension, the infarcted area was correlated with the number of homed MMNCs in a model of experimental cryodamaged heart. STUDY DESIGN AND METHODS: A total of 12 donor and 12 recipient inbred isogenic adult (4 weeks old) Fisher rats were used to mimic autologous trans- plantation. Myocardial damage was obtained in recipient rats by cryoinjury. MMNCs were purified, labeled with PKH26 (a red fluorescent cell dye), and infused 7 days after the injury through the femoral vein of recipient rats. One week after peripheral administration, the number of homed MMNCs was assessed and the infarct size was correlated with the number of cells present in the target. RESULTS: Labeled cells were found only in the injured myocardium of the treated animals (n = 6), where a mean of 12 ± 3 PKH26+ cells per section examined were found; a significant correlation was found between the infarct size and the estimated number of cells (p = 0.008) CONCLUSION: These data indicate that the homing of MMNCs is related to the extent of the myocardial injury, suggesting that cellular therapy for regeneration of damaged myocardium should be individualized by taking into consideration the extension of the area to repair. ecently, a number of in vitro and in vivo studies reported that marrow contains multipotent progenitor cells, capable not only of colonizing different tissues, but also of proliferating and transdifferentiating into cell lineages of host organs, including osteocytes,chondrocytes,adipocytes, myo- cytes, and even cardiomyocytes. 1-6 This fact implies that marrow represents a reservoir of progenitor cells that in steady state circulate at low to undetectable levels, while perturbations of the hemato- poietic system, such as those resulting from chemother- apy, 7 or administration of cytokines such as G-CSF, 8 lead to a transient increase in the number of circulating pro- genitor cells. These evidences opened a new perspective in cytokine-induced cardiac repair by administration of G- CSF as mobilizing factor. 9 Recently, the cytokine mobiliza- tion axis has been described by Levesque et al. 10 Because myocardial infarction is associated with a marked activa- tion of the cytokines cascadeand their production is proportional to the damaged tissue extension, 11 it seems R