Ethel J. Ngen
Johns Hopkins University School of Medicine, USA
Title: Molecular Imaging Biosensors for Precise Therapeutic Interventions in Regenerative Medicine
Biography
Biography: Ethel J. Ngen
Abstract
Precision medicine aims to provide personalized treatment plans tailored to the specific needs of individual patients. With the growing need for more personalized therapeutic regimens in regenerative medicine, we will demonstrate the importance of cellular imaging biosensors to noninvasively visualize, characterize, and quantify the effective delivery, biodistribution, survival, and engraftment of transplanted stem cells in vivo. The applicability of a novel dual-contrast magnetic resonance imaging (MRI) technique to noninvasively image transplanted stem cells will be discussed. This dual-contrast MRI technique involves two different classes of MRI contrast agents, possessing different diffusion coefficients: high-molecular-weight superparamagnetic iron oxide nanoparticles (SPIONs; T2/T2* contrast agents, with low diffusion coefficients) and low-molecular-weight gadolinium chelates (T1 contrast agents, with high diffusion coefficients). Human mesenchymal stem cells were dual labeled with SPIONs and a gadolinium-based chelate (GdDTPA). The viability, proliferation rate, and differentiation potential of the labeled stem cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead stem cells was next evaluated using MRI phantoms. We next evaluated the efficiency of this technique to image transplanted stem cells in vivo in both immune-competent and immune-deficient mice, following the induction of radiation-induced brain injury in the mice. All MRI results were validated with bioluminescence imaging. In Immune-deficient mice where the transplanted stem cells survived, and both contrast agents were in close proximity, the T2/T2* contrast from the SPIONs predominated and the T1 contrast from the gadolinium chelates was quenched. This T2/T2* MRI contrast was used to track stem cell delivery and stem cell migration. In immune-competent mice where the stem cell died following transplantation, a diffused positive (T1) MRI contrast was generated in the vicinity of the dead cells and served as an imaging marker for cell death (Figure 1). Ultimately, this technique could be used to manage and personalize stem cell therapies in regenerative medicine.