Mesenchymal stem cell administration at coronary artery reperfusion in the rat by two delivery routes: a quantitative assessment

Abstract

Aims: Ideally, mesenchymal stem cells (MSC) home to and/or remain at the site of damaged myocardium when administered after myocardial infarction. However, MSC may not remain in the heart, but instead relocate to other areas. We investigated quantitatively the distribution of labeled rat MSC, given by two routes after coronary artery occlusion/reperfusion in rats.

Main methods: Rats were subjected to 45 min of coronary artery occlusion and 7 days of reperfusion. Before reperfusion rats received 2 x 10(6) MSC, labeled with europium, injected directly into the ischemic region of the heart (n = 9) or intravenously (n = 8). After 1 week tissues were analyzed for label content together with a standard curve of known quantities of labeled MSC.

Key findings: In rats receiving cells injected directly into the myocardium, 15% of labeled cells were retained in the heart. When the cells were administered intravenously, no MSC were detected in the heart. The route of administration did not affect distribution to other organs, as the number of MSC in liver, spleen and lung was similar with both routes of delivery.

Significance: Even with direct intramyocardial injection, only a small proportion of the cells are retained in the heart, instead traveling to other organs. With intravenous injection there was no evidence that cells "homed" to the damaged heart. Although cell delivery to the heart was significantly affected by the route of administration, the distribution of cells to other organs was similar with both routes of administration.

Figure 1

The relationship between the number of cells and the disintegrations per minute in the standard curve from one expansion. The formula for the relationship is expressed as: (cell number = 1.81 (disintegration per minute) + 3517). The variables were linearly related and showed an excellent correlation (r = 0.99)

Figure 2

Median number of labeled cells detected in liver, lung, spleen and kidney (per gram of tissue) when MSC were administered intravenously or directly into the myocardium. Analyzed by non-parametric statistics (Wilcoxon test) there were no significant differences in the accumulation of cells in these organs based on route of cell delivery.