An Implantable Human Stem cell-derived Tissue-engineered Rostral Migratory Stream for Directed Neuronal Replacement

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Departmental Papers (Dental)
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Animals
Astrocytes
Humans
Male
Neural Stem Cells
Neurogenesis
Neurons
Rats
Rats
Nude
Tissue Engineering
animal
astrocyte
human
male
nerve cell
nervous system development
neural stem cell
nude rat
physiology
rat
tissue engineering
transplantation
Dentistry
Oral and Maxillofacial Surgery
Other Dentistry
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O'Donnell, John C
Purvis, Erin M
Helm, Kaila VT
Adewole, Dayo O
Zhang, Qunzhou
Le, Anh D
Cullen, Kacy D
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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. © 2021, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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2021-12-01
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Communications Biology
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