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Case Center For Imaging Research

Molecular Imaging Research

 
 
Case Western Reserve University and University Hospitals Health System

 

In Vitro Evaluation of Imaging Potential of Mesenchymal Stem Cell Transplantation Following NIS Transfer

Mesenchymal Stem Cells (MSCs) found in human bone marrow are able to proliferate extensively in vitro without loss of differentiation potential. They represent a novel cellular therapy of inherited or degenerative diseases. We have demonstrated that culture-expanded autologous and allogeneic MSCs can be safely infused into humans and the preliminary results showed that MSCs facilitate hematopoietic engraftment and reduce graft versus host disease (GVHD). However, there is insufficient information about in vivo distribution and survival of intravenously infused MSCs and, their contribution to normal tissue function. In this in vitro study, we tested the feasibility of using Na+/I- symporter (NIS) gene, normally expressed in the thyroid gland as shown on the right, as a reporter gene for the eventual in vivo imaging of MSCs’ distribution and persistence, simply with radioiodide or equivalent (such as the pertechnetate) as tracer.

Human MSC (hMSC) cultures were established from bone marrow aspirate specimens, and were transduced with NIS gene using lentiviral vector wpts.hNIS as shown below.

The radioiodide uptake increased up to 30+ fold in NIS-hMSC comparing with wt hMSC, and the amount of uptake was proportional to the number of the cells as shown below.
Such uptake was inhibited completely by NaClO4, a known NIS specific inhibitor, as shown below. The in vitro half lives (retention) of radioiodide in NIS-hMCS was 7 min, also shown below.