Washout of transplanted cells from the heart: a potential new hurdle for cell transplantation therapy.
OBJECTIVE
The number of viable transplanted cells in the heart is sharply decreased shortly after cell injection. The exact mechanics of cell loss are unclear. We hypothesized that immature cardiac cells transplanted directly into rat heart could be washed out via the cardiac vasculature, and carried to other organs.


METHODS
Female Fischer rats were subjected to 60 min of coronary artery occlusion followed by 3 h of reperfusion (OR group) or 4 h or permanent coronary artery occlusion (PO group). Neonatal rat cardiac cells (5x10(6)) were injected directly into the free wall of the left ventricle at either 15 min post-reperfusion (OR group) or 75 min after occlusion (PO group). At the end of the protocol, a histological analysis for transplanted cells in the heart (i.e. microscopic examination for cells in approximately 790 histogic fields within each heart) and polymerase chain reaction (PCR)-based determination of the Sry gene (a male cell marker) in the heart and other organs were performed.


RESULTS
In the OR group, only 3.39+/-0.69% fields contained immature cells compared to 6.57+/-1.33% fields in the PO group (p<0.05). Cardiac blood vessels contained round, immature cardiomyocytes. PCR analysis revealed that 100% of the animals (5 of 5) in both groups had cells present in their hearts and lungs, 40% of the OR group and 60% of the PO group demonstrated cells in the liver and kidneys, and 40% of the PO group had cells in the spleen.


CONCLUSIONS
Neonatal cardiomyocytes injected directly into the area at risk of the heart escape acutely from the infract to other organs through the vascular system of the heart; loss of cells is more prominent with reperfusion.
Dow
Joan
J
Heart Institute, Good Samaritan Hospital, 1225 Wilshire Boulevard, Los Angeles, CA 90017, USA.
Simkhovich
Boris Z
BZ
Kedes
Larry
L
Kloner
Robert A
RA
D000818:Animals; D002452:Cell Count; D003326:Coronary Circulation; D005260:Female; D005819:Genetic Markers; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000637:transplantation*; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344; D014998:Y Chromosome
D005819:Genetic Markers