Hydrogel-based scaffolds to support intrathecal stem cell transplantation as a gateway to the spinal cord: clinical needs, biomaterials, and imaging technologies

The prospects for cell replacement in spinal cord diseases are impeded by inefficient stem
cell delivery. The deep location of the spinal cord and complex surgical access, as well as
densely packed vital structures, question the feasibility of the widespread use of multiple
spinal cord punctures to inject stem cells. Disorders characterized by disseminated
pathology are particularly appealing for the distribution of cells globally throughout the
spinal cord in a minimally invasive fashion. The intrathecal space, with access to a
relatively large surface area along the spinal cord, is an attractive route for global stem cell
delivery, and, indeed, is highly promising, but the success of this approach relies on the
ability of cells 1) to survive in the cerebrospinal fluid (CSF), 2) to adhere to the spinal cord
surface, and 3) to migrate, ultimately, into the parenchyma. Intrathecal infusion of cell
suspension, however, has been insufficient and we postulate that embedding
transplanted cells within hydrogel scaffolds will facilitate reaching these goals. In this
review, we focus on practical considerations that render the intrathecal approach clinically
viable, and then discuss the characteristics of various biomaterials that are suitable to
serve as scaffolds. We also propose strategies to modulate the local microenvironment
with nanoparticle carriers to improve the functionality of cellular grafts. Finally, we
provide an overview of imaging modalities for in vivo monitoring and characterization of
biomaterials and stem cells. This comprehensive review should serve as a guide for those
planning pre-clinical and clinical studies on intrathecal stem cell transplantation.