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

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Abstract
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.
Funding Information
  • National Science Foundation (DGE-1845298)
  • Michael J. Fox Foundation for Parkinson’s Research (Therapeutic Pipeline Program #9998)
  • United States Department of Defense | United States Army | Army Medical Command | Medical Research and Materiel Command (W81XWH-16-1-0796)
  • Center for Undergraduate Research and Fellowships at the University of Pennsylvania

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