To Recruit or To Graft? -Comparing the recruitment of resident non-neuronal cells by lineage reprogramming with engraftment of stem cell-derived neurons for neuronal replacement therapies

Daniel A Peterson^*

• Rosalind Franklin University of Medicine and Science, North Chicago, United States

Neurons are post-mitotic cells that are not replaced once lost, leading to the need forneuronal replacement therapies for central nervous system (CNS) repair. The generation ofinduced pluripotent stem cell (iPSC) derived human neurons is relatively advanced, withthe capacity to generate pure and validated populations of diYerent neuronal subtypes asclinical grade cells ready for engraftment. Clinical trials using human-derived embryonicstem cells (hESC) and iPSC-derived neurons are underway. As an alternative approach,the ability to target in vivo resident non-neuronal cells with reprogramming factors toinduce replacement neurons has been demonstrated. The ability to engineer a definedpopulation of resident replacement neurons that retain their cytoarchitectural locationmay permit an additional, more focused therapeutic strategy for specific circuits that couldcomplement the bulk engraftment of ex vivo stem cell-derived replacement neurons. Thismini-review summarizes and compares these two strategies and oYers a perspective onthe steps needed to advance recruitment as a complementary therapeutic strategy.