In Vitro Monitoring of Cardiomyogenic Differentiation of Mesenchymal Stem Cells using Sodium Iodide Symporter Gene

Abstract

There is a need for non-invasive monitoring the differentiation of transplanted cell in stem cell therapy. In this study, we evaluated the usefulness of sodium iodide symporter (NIS) gene as molecular imaging reporter gene during cardiomyogenic differentiation of bone marrow derived mesenchymal stem cells (BMSCs). In a previous study, we showed that a transgenic mouse model expressing NIS driven by the alpha-myosin heavy chain (alpha-MHC) promoter was developed to image cardiomyocytes in vivo with a gamma-camera and micro positron emission tomography (microPET). BMSCs were found to express stem cell specific surface markers including stem cell antigen-1 (Sca-1) and CD44. After treatment with all-trans retinoic acid (ATRA), BMSCs morphologically changed and acquired a cardiomyocyte-like shape. The cardiomyogenic differentiation of BMSCs resulted in upregulated expression of cardiac specific genes including alpha-MHC and ventricular myosin light chain 2 (MLC-2v) and decreased expression of the stem cell specific marker, Sca-1. The ATRA treated BMSCs exhibited higher I-125 uptake than that of non-treated cells, and this result suggested that the cardiomyogenic differentiation upregulated NIS gene activity as reporter in vitro. We demonstrated that, under the control of the alpha-MHC promoter, NIS activity reflected cardiomyogenic differentiation of BMSCs in vitro, and an imaging system based on NIS, the reporter gene, may be a useful tool for monitoring in the lineage specific differentiation of stem cells.