Homing of peripherally injected bone marrow cells in rat after experimental myocardial injury.
OBJECTIVE
Significant progress has been achieved during the past 10 years in cell transplantation and recent research has focused on the possibility of improving ventricular function after myocardial infarction. Most studies in the field of cardiac tissue repair are performed by direct intramyocardial injection of cells of different origin. Since this approach requires a surgical intervention, in this study we investigated the feasibility of non-invasive administration of bone marrow mononuclear cells (BMMNCs) by assessing the fate of peripherally injected, purified, labeled cells in cryodamaged hearts.


METHODS
Ten donor and ten recipient inbred isogenic adult (4 weeks old) Fisher rats were used as models to mimic autologous transplantation. Myocardial damage was obtained in recipient rats by placing a frozen metal probe on the anterior left ventricular wall for 15 seconds (freeze-thaw injury technique). BMMNCs were purified and labeled with a red fluorescent cell dye. Seven days after the injury about 15-25x10(6) cells were infused through the femoral vein of recipient rats. Seven days after the infusion, the heart, lungs, liver, kidneys, spleen and thymus were harvested to track transplanted cells.


RESULTS
Labeled cells were found only in the injured area of the heart and not in the normal tissue, and a limited number of cells were identified in the spleen of all the animals. Most of the labeled cells in the infarcted area were Thy-1(+) and some were CD34(+).


CONCLUSIONS
Our data suggest that peripherally injected BMMNCs can traffic through the circulation to the site of damage; we hypothesize that tissue injury leads to the priming of a cytokine cascade acting as chemoattractant for the infused cells.
Ciulla
Michele M
MM
Istituto di Clinica Medica Generale e Terapia Medica, Centro di Fisiologia Clinica e Ipertensione, Università di Milano, IRCCS Ospedale Maggiore di Milano, Milan, Italy. michele.ciulla@unimi.it
Lazzari
Lorenza
L
Pacchiana
Raffaella
R
Esposito
Arturo
A
Bosari
Silvano
S
Ferrero
Stefano
S
Gianelli
Umberto
U
Paliotti
Roberta
R
Busca
Giuseppe
G
Giorgetti
Alessandra
A
Magrini
Fabio
F
Rebulla
Paolo
P
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D007267:Injections; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology; D014463:Ultrasonography