Imaging gene expression in human mesenchymal stem cells: from small to large animals

Area of Science:

• Regenerative Medicine
• Biomedical Imaging
• Molecular Imaging

Background:

• Human mesenchymal stem cells (MSCs) are promising for cardiac repair.
• Non-invasive imaging is crucial for tracking MSCs after transplantation.
• Reporter gene imaging allows visualization of gene expression in transplanted cells.

Purpose of the Study:

• To assess the feasibility of reporter gene imaging in human MSCs implanted in porcine myocardium.
• To evaluate the utility of clinical positron emission tomography (PET)-computed tomography (CT) scanning for this purpose.

Main Methods:

• Human MSCs were transduced with a reporter gene (HSV1-sr39tk) using adenovirus.
• Cell cultures were used to characterize gene expression and radiotracer uptake.
• Transduced MSCs were injected into rat and swine myocardium.
• Imaging was performed using micro-PET and clinical PET-CT with FHBG radiotracer.

Main Results:

• Reporter gene expression and radiotracer accumulation increased with viral dose in cell culture.
• Significant elevation of cardiac FHBG uptake was observed in rats post-MSC injection.
• In swine, myocardial radiotracer uptake was not elevated without a scaffold.
• Using matrigel as a scaffold improved signal-to-background ratio in swine, correlating with MSC number.

Conclusions:

• Reporter gene imaging of human MSCs is translatable to large animal models.
• Co-administration of a scaffold is essential for enhancing intramyocardial retention and imaging of MSCs.