hiPSC-derived Neural Stem/Progenitor Cells in Chronic Cervical Spinal Cord Injury

Abstract

hiPSCs have the potential to provide plentiful autologous cells for clinical translation to spinal cord injury, but substantial hurdles remain. The necessary conditions for effective cell replacement and plasticity to occur in a safe manner are yet to be determined. This work evaluated the use of hiPSCs at three different differentiation states as potential therapeutic agents in chronic cervical spinal cord injury, a condition for which current treatment modalities are mostly ineffective. While driving hiPSCs to a fully differentiated state (i.e. astrocytes), with specific regional, morphological and phenotypic features, was feasible in vitro, hiPSC-derived astrocytes did not prove to be an effectively transplantable resource. Multipotent caudalized hiPSC-NPCs engrafted well into the hostile lesion environment and differentiated into multiple neural and glial cell types in vivo that translated into only modest functional recovery. Finally, transplantation of hiPSC-NSCs showed that broad differentiation potential brings a concomitant risk of overgrowth. Finding a balance between competency and unchecked proliferation will be key to effectively and safely realizing the potential of hiPSCs in spinal cord injury. Additionally, there is a need for solid preclinical foundation and demonstration of safety (both biological and procedural) before clinical trials can be attempted. Despite these caveats, hiPSC-derived neural cells still show promise as a means of inducing cellular plasticity in a vastly underserved population of patients suffering from chronic cervical SCI.