Transplantable human motor networks as a neuron-directed strategy for spinal cord injury

• Published in: iScience 2021-08, Vol.24 (8), p.102827-102827, Article 102827
• Main Authors: Olmsted, Zachary T., Stigliano, Cinzia, Scimemi, Annalisa, Wolfe, Tatiana, Cibelli, Jose, Horner, Philip J., Paluh, Janet L.
• Format: Article
• Language: English
• Subjects: Bioengineering; Neuroscience; Tissue engineering
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2021.102827

To repair neural circuitry following spinal cord injury (SCI), neural stem cell (NSC) transplantation has held a primary focus; however, stochastic outcomes generate challenges driven in part by NSC differentiation and tumor formation. The recent ability to generate regionally specific neurons and their support cells now allows consideration of directed therapeutic approaches with pre-differentiated and networked spinal neural cells. Here, we form encapsulated, transplantable neuronal networks of regionally matched cervical spinal motor neurons, interneurons, and oligodendrocyte progenitor cells derived through trunk-biased neuromesodermal progenitors. We direct neurite formation in alginate-based neural ribbons to generate electrically active, synaptically connected networks, characterized by electrophysiology and calcium imaging before transplantation into rodent models of contused SCI for evaluation at 10-day and 6-week timepoints. The in vivo analyses demonstrate viability and retention of interconnected synaptic networks that readily integrate with the host parenchyma to advance goals of transplantable neural circuitry for SCI treatment. [Display omitted] •Neuromesodermal progenitor derivation of human spinal neurons as therapeutic cells•Neural ribbons bridge in vitro network formation and in vivo host transplantation•In vivo visualization of encapsulated graft placement with magnetic resonance imaging•Six-week viability of human neuronal networks with OPCs in rat contusion SCI Neuroscience; Bioengineering; Tissue engineering