Stem Cell Imaging – Translational Approaches
Heike Daldrup-Link, M.D., Ph.D.
Stem Cell Therapy has the potential to revolutionize modern medicine by providing unprecedented opportunities for reconstitution of previously incurable diseases and tissue injuries. The field is continuously expanding and rapidly entering clinical applications, with currently over 4000 ongoing clinical stem cell trials worldwide for the treatment of over 1400 diseases. Imaging will be most useful for monitoring those therapeutic cells, which are designed to persist long-term (months to years) in vivo. Therapeutic cells migrate, proliferate, differentiate, and respond to their environment in vitro and in vivo. Despite great promises from pre-clinical applications, there are many open questions regarding safe applications of therapeutic cells in patients: (1) Imaging tools need to diagnose stem cell delivery and engraftment at the target site and in addition, be sensitive enough to detect cell migrations to other sites. A variety of translational MR, SPECT and PET imaging tools have been developed for this purpose. (2) In order to determine whether a patient needs repeat dosing or other interventions, more sophisticated biomarkers are needed which provide additional information about the quantity, viability and long-term survival of the transplanted cells. (3) The propagation of autologous “off the shelf” cell therapeutics adds an urgent need of clinically applicable diagnostic tools for detection of immune responses to stem cell transplants. Immediately clinically applicable immune cell tracking techniques and label-free imaging approaches based on cell type–specific markers are under development for this purpose. (4) There is an unmet need of clinical imaging technologies for in vivo detection of stem cell differentiation processes towards undesired differentiation outcomes. Especially for cell products derived from pluripotent cells, we need clinical imaging tools for in vivo detection of contaminating pluripotent cells, which may give rise to teratoma or other tumor formations. Biomarkers for cell proliferation would further facilitate early tumor detection and therapeutic interventions. (5) Desired tissue regeneration outcomes can be diagnosed with the help of cell-lineage specific biomarkers, integrated with state-of-the art clinical expertise about morphological and functional target tissue characteristics.
In summary clinical cell tracking tools will improve monitoring of stem cell transplants in patients, enable clinicians to optimize stem cell delivery and retention, help to detect complications at an early stage and ultimately, improve tissue repair outcomes and related disabilities.