@article{fdbd7c1403d44efc961ed235d9d6f4ca,
title = "Transplantable human motor networks as a neuron-directed strategy for spinal cord injury",
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.",
keywords = "Bioengineering, Neuroscience, Tissue engineering",
author = "Olmsted, {Zachary T.} and Cinzia Stigliano and Annalisa Scimemi and Tatiana Wolfe and Jose Cibelli and Horner, {Philip J.} and Paluh, {Janet L.}",
note = "Funding Information: This work was funded by the New York State Department of Health (NYS DOH) Spinal Cord Injury Research Board (NYSCIRB), Projects to Accelerate Research Translation (PART) award C33278GG and SUNY Polytechnic SEED award 917035-21 and used a published line developed through previous New York State stem cell research (NYSTEM) funding. This work was also supported by NSF/IOS1655365 and SUNY Albany Research Foundation grants to A.S. J.P. and Z.O. designed experiments and wrote the manuscript with input from all co-authors. Z.O. compiled figures, and performed hiPSC maintenance, neural differentiation and analysis, neural ribbon studies and shipping, in vitro imaging, electrophysiology sample preparation, and MEA experiments. A.S. performed patch clamp experiments and analysis. C.S. and P.H. conducted in vivo grafting studies and data acquisition. T.W. assisted with MRI. The F3.5.2 hiPSC line was previously derived in collaboration with J.C. who also provided key input for experiments and the final manuscript. The authors declare no competing interests. Multiple authors on this paper received support from a program NYSTEM designed to increase minority representation in science. The research in this paper includes work with ethnically diverse human iPS lines generated from that support. In order to bring increased representation of the diverse U.S. and global populations to stem cell research, multiple authors on this paper have played an integral role in the reprogramming, characterization, and application of iPSC lines from self-reported African American, Hispanic Latino, and Asian fibroblast donors. These lines represented the first such lines of their kind, and the African American line F3.5.2 is applied here in this iScience study. Furthermore, lines from all three donors have been used in numerous other publications, including generation of the first gastruloids, termed ?elongating multi-lineage organized (EMLO) gastruloids?, published in Nature Communications (PMID: 34021144). Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = aug,
day = "20",
doi = "10.1016/j.isci.2021.102827",
language = "English (US)",
volume = "24",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier",
number = "8",
}