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Restorative effects of human neural stem cell grafts on the primate spinal cord

Abstract

We grafted human spinal cord–derived neural progenitor cells (NPCs) into sites of cervical spinal cord injury in rhesus monkeys (Macaca mulatta). Under three-drug immunosuppression, grafts survived at least 9 months postinjury and expressed both neuronal and glial markers. Monkey axons regenerated into grafts and formed synapses. Hundreds of thousands of human axons extended out from grafts through monkey white matter and synapsed in distal gray matter. Grafts gradually matured over 9 months and improved forelimb function beginning several months after grafting. These findings in a 'preclinical trial' support translation of NPC graft therapy to humans with the objective of reconstituting both a neuronal and glial milieu in the site of spinal cord injury.

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Figure 1: Graft concept, procedure, survival, and differentiation.
Figure 2: Changes in graft density and cell size.
Figure 3: Axon emergence from grafts.
Figure 4: Host axons regenerate into human NPC grafts.

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Acknowledgements

Human 566RSC-UBQT neural stem cells were a gift from NeuralStem, Inc. This work was supported by the Veterans Administration (Gordon Mansfield Spinal Cord Injury Collaborative Consortium, RR&D B7332R, MHT; RR&D RX001045, JHB), the National Institutes of Health (R01 NS042291, MHT; R01 NS104442, MHT), the Department of Defense (W81XWH-12-1-0592; E.S.R.), the Craig H. Neilsen Foundation (M.H.T.), the Bernard and Anne Spitzer Charitable Trust (M.H.T.), and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (M.H.T.).

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Authors

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E.S.R., J.H.B., P.L., E.A.S., K.K., L.A.H., Y.S.N.-L., A.R.F., M.S.B., J.C.B., and M.H.T. designed the experiments. E.S.R., J.H.B., P.L., H.K., E.A.S., K.K., R.M., S.H., Y.S.N.-L., J.C.B., and M.H.T. carried out the experiments. E.S.R., J.H.B., H.K., E.A.S., J.L.W., J.J.L., J.R.H., L.A.H., A.R.F., and M.H.T. analyzed the data. E.S.R. and M.H.T. wrote the manuscript. E.S.R., J.H.B., P.L., H.K., E.A.S., K.K., J.L.W., J.J.L., R.M., S.H., J.R.H., L.A.H., Y.S.N.-L., A.R.F., M.S.B., J.C.B., and M.H.T. edited the manuscript.

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Correspondence to Mark H Tuszynski.

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Rosenzweig, E., Brock, J., Lu, P. et al. Restorative effects of human neural stem cell grafts on the primate spinal cord. Nat Med 24, 484–490 (2018). https://doi.org/10.1038/nm.4502

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