Recent developments and future challenges on imaging for stem cell research

Abstract

As clinical trials with stem cells for cardiac regenerative therapy move forward, advances in imaging equipment and technique offer powerful methods to evaluate therapeutic efficacy. Methodologies to label stem cells for tracking continue to expand. Non-invasive imaging offers the potential to better understand the interaction of exogenous stem cells with the host to answer questions such as the best cell type(s), timing of delivery, dose, and delivery route. If successful, these techniques may enable individually tailored dosing of stem cell therapeutics. However, techniques that are suitable for animal models of cardiac disease may have hurdles to clinical translation beyond simple biocompatibility issues. Challenges include the high cost of advanced imaging techniques, applicability in acute ischemic disease, and regulatory approval. In this review, we will cover some new imaging techniques and labeling strategies and assess the obstacles to clinical adoption.

Keywords: CT Imaging; Magnetic Resonance Imaging; Radionuclide Imaging; Reporter Gene Imaging; Stem Cells.

Fig. 1

Electromechnical-mapping-guided mesenchymal stem cell delivery in a swine myocardial infarction (MI) model. a Endocardial mapping of a pig heart 16 days after MI. MSCs transfected with a truncated thymidine kinase reporter gene were intramyocardially injected into the border zone of the infarction (white arrows), and unlabeled MSCs were delivered into noninfarcted posterior wall (yellow arrow). b ¹³N-ammonia positron emission tomography with transmission scan of the pig heart showing perfusion defect in the anterior wall and apex 16 days after MI. c The location of two injection sites of reporter gene transfected MSCs are demonstrated by¹⁸F-FHBG PET image of the pig heart 8 h after injection. Unlabeled MSCs could not be detected. d Registration of ¹⁸F-FHBG PET (hot scale) with MRI (gray scale) demonstrating tracer uptake only at MSCs injection sites. Reprinted from Gyöngysi et al. [17] with permission

Fig. 2

X-ray angiogram of the rabbit peripheral hindlimb before intervention (a) and after femoral artery occlusion using a platinum coil (black arrow; b). X-ray visible, mesenchymal stem cells containing microcapsules appear as radiopacities in the medial thigh of the rabbit after intramuscular delivery (b). Q quarter for reference of size and opacity. Reprinted from Nahrendorf et al. [30] with permission

Fig. 3

Bioluminescence images of the medial thigh of a rabbit model of peripheral arterial disease provides the ability to assess cell viability in vivo of intramuscularly injected X-ray-visible encapsulated mesenchymal stem cells that were transfected with a reporter gene as well as nonencapsulated reporter gene transfected MSCs. Reprinted from Tsui and Kraitchman [40] with permission