Abstract 514: Homing of Mesenchymal Stem Cells Following Intravenous Injection: The Wrong Approach for Cell Delivery to Infarcted Myocardium? A Quantitative Assessment Using Nanoparticle Labeling
Mesenchymal stem cells (MSC) may have the ability to home to the site of injury when administered intravenously after myocardial infarction (MI) and to repair necrotic myocardium. However, whether MSC can survive and target the myocardium when transplanted immediately after MI is uncertain. Purpose: To test the distribution of rat MSC quantitatively when given by two routes of administration immediately after myocardial infarction in rats.
Methods: MI was induced in Fisher rats, and 10 min after coronary artery occlusion rats randomly received 2 million rat MSC, labeled with isotopic colloidal nanoparticles (europium), injected either directly into the infarcted region of the heart (n=5) or intravenously via the tail vein (n = 6). After 4 days tissues were obtained from infarcted and non-infarcted myocardium and from lung, kidney, spleen, and liver. Tissues were desiccated and analyzed for europium label together with known quantities of labeled MSCs alone (Biophysics Assay Laboratory, Worcester, MA).
Results: In rats receiving MSC injected directly into the heart, europium label was observed in 5/5 rats in the infarcted region of the heart (mean value equivalent to ~ 500,000 cells) at day 4. No label was present in non-infarcted myocardium or in other tissues. In contrast, in rats receiving IV administration of MSC, no label was present in either region of the heart, however label was observed in the liver of 4/6 rats (mean value equivalent to ~200,000 cells) and in the spleen of 1/6 rats.
Conclusion: When administered immediately after myocardial infarction, direct injection of MSC resulted in 25 % of the labeled cells remaining in the heart after 4 days. When administered IV, no labeled cells were detected in the heart, but label was present only in liver and spleen. Thus IV injection of cells may not be an appropriate route of delivery as a treatment immediately after myocardial infarction; direct intramyocardial wall injection appears superior.