A new in vivo/in vitro model for assessing the capacity of human derived oral mucosa stem cells to colonize the infarcted myocardium

Abstract

Ischemic heart failure (IHF) is a leading cause for mortality and morbidity worldwide. Stem cell (SC) therapy is a promising strategy for IHF treatment. A major prerequisite for successful SC therapy is homogenous colonization of the infarcted myocardium. This process implies SC migration from the transplantation site. The purposes of the present study were to develop a new model system capable of quantifying SC migration within the infarcted myocardium and to assess the effect of post myocardial infarction (MI) remodeling on the migration of a newly identified neural crest SC population derived from the oral mucosa (hOMSC). MI was induced in rats. Myocardial scar tissue was collected at 0,1,3,7,14, and 28 days post-MI. DiI-labeledhOMSC were injected in the center of cylindrical scar tissue specimens harvested from each post-MI time point and transferred to organ culture. Changes in host and hOMSC cell densities were quantified in the center and periphery of specimens after 0, 3, 7, 14, and 28 days of culture by morphometric fluorescence microscopy. The results indicate a decrease in hOMSC density in the central zone and an increase in density in the peripheral zones indicating hOMSC migration from the central transplantation site to the rest of the infarcted myocardium. The average hOMSC density increased overtime due to cell proliferation. The level of hOMSC migration and proliferation was significantly affected by post-MI remodeling phase being higher in post-MI tissue that still comprised cardiomyofibers than in granulation and fibrotic tissues. Preliminary hOMSC transplantation in nude rat supports these findings. The present study shows that the new in vivo/in vitro model system is sufficiently sensitive to detect and quantify changes in the migratory capacity of stem cells within the infarcted myocardium and suggest that cell therapy applied in the early stages (up to 3 days) of post-MI remodeling facilitates the process of tissue colonization.