Molecular imaging-guided regenerative medicine: visualizing in vivo functional behaviors of grafted stem cells

In the past few decades, the global community has witnessed rapid advances of regenerative medicine, in which stem cell therapy exhibits great potential for clinical translation. However, there remains challenges, such as low cell survival rate, insufficient directed migration, and uncontrollable differentiation, restricting fast clinical applications. To solve these problems, it is necessary to track grafted stem cells in vivo, especially monitoring functional behaviors after transplantation and uncovering the inner mechanisms, which further promote evaluation of the therapeutic efficacy and safety for clinical practice. Molecular imaging is a revolutionary technique with advantages of non-invasive, real-time quantitative, and multimodal integration. It can transfer cell behaviors and biological changes into the visible image data, solving the key issues in regenerative medicine, including cell fate tracking, function recovery evaluation, and safety monitoring. Therefore, resolving in vivo functional behaviors of grafted stem cells through molecular imaging can enormously accelerate translation of stem cell therapy for clinical practice.

Visualizing in vivo functional behaviors of stem cells

Survival and proliferation

The in vivo survival and proliferative capacity of stem cells are the fundamental determinants of therapeutic efficacy. Through engineered reporter systems, such as luciferase for bioluminescent survival mapping and thymidine kinase derivatives for positron emission tomography (PET)-based proliferation quantification, molecular imaging reveals spatiotemporal patterns of cell survival, metabolism, division, and proliferation. Neural progenitors integrated with firefly luciferase and herpes simplex virus thymidine kinase were transplanted into infarcted brains, of which the engraftment and proliferation were monitored by both bioluminescence and PET imaging.1 Additionally, [11C]methionine and [18F]fluorothymidine PET can also help visualize stem cell proliferation in vivo, due to the high demand of amino acids and nucleotides during proliferation.

Migration and homing

The targeted migration and precise homing of stem cells to injury sites are pivotal for achieving functional tissue repair for regeneration. By utilizing multimodal systems, such as fluorescent proteins combined with magnetic resonance imaging (MRI) and PET, molecular imaging can capture spatiotemporal migration kinetics, chemoattractant-driven navigation, and niche-specific engraftment selectivity. Mesenchymal stem cells (MSCs) labeled with superparamagnetic iron oxide nanoparticles were tracked in vivo in a mouse model of inflammatory bowel disease.2 MRI provided dynamic tracking of MSC distribution, viability, and homing, revealing better performance through the intraperitoneal route. It effectively contributed to the preferred administration pathway in stem cell therapy guided by visualization of migration and homing.