An implantable human stem cell-derived tissue-engineered rostral migratory stream for directed neuronal replacement

The rostral migratory stream (RMS) facilitates neuroblast migration from the subventricular zone to the olfactory bulb throughout adulthood. Brain lesions attract neuroblast migration out of the RMS, but resultant regeneration is insufficient. Increasing neuroblast migration into lesions has improved recovery in rodent studies. We previously developed techniques for fabricating an astrocyte-based Tissue-Engineered RMS (TE-RMS) intended to redirect endogenous neuroblasts into distal brain lesions for sustained neuronal replacement. Here, we demonstrate that astrocyte-like-cells can be derived from adult human gingiva mesenchymal stem cells and used for TE-RMS fabrication. We report that key proteins enriched in the RMS are enriched in TE-RMSs. Furthermore, the human TE-RMS facilitates directed migration of immature neurons in vitro. Finally, human TE-RMSs implanted in athymic rat brains redirect migration of neuroblasts out of the endogenous RMS. By emulating the brain’s most efficient means for directing neuroblast migration, the TE-RMS offers a promising new approach to neuroregenerative medicine. O’Donnell et al. describe their Tissue-Engineered Rostral Migratory Stream (TE-RMS) comprised of human astrocyte-like cells that can be derived from adult gingival stem cells within one week, which reorganizes into bundles of bidirectional, longitudinally-aligned astrocytes to emulate the endogenous RMS. Establishing immature neuronal migration in vitro and in vivo, their study demonstrates surgical feasibility and proof-of-concept evidence for this nascent technology.