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

Zachary T. Olmsted, Cinzia Stigliano, Annalisa Scimemi, Tatiana Wolfe, Jose Cibelli, Philip J. Horner, Janet L. Paluh

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number102827
JournaliScience
Volume24
Issue number8
DOIs
StatePublished - Aug 20 2021

Keywords

  • Bioengineering
  • Neuroscience
  • Tissue engineering

ASJC Scopus subject areas

  • General

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