Safety of direct injection of oligodendrocyte progenitor cells into the spinal cord of uninjured Göttingen minipigs

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  • 1 Department of Neurosurgery, Rush University Medical Center, Chicago, Illinois;
  • | 2 USC Neurorestoration Center, Los Angeles;
  • | 3 Department of Neurosurgery, Stanford University, Palo Alto; and
  • | 4 Asterias Biotherapeutics, a wholly owned subsidiary of Lineage Cell Therapeutics, Carlsbad, California
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OBJECTIVE

This study was conducted as a final proof-of-safety direct injection of oligodendrocyte progenitor cells into the uninjured spinal cord prior to translation to the human clinical trials.

METHODS

In this study, 107 oligodendrocyte progenitor cells (LCTOPC1, also known as AST-OPC1 and GRNOPC1) in 50-μL suspension were injected directly into the uninjured spinal cords of 8 immunosuppressed Göttingen minipigs using a specially designed stereotactic delivery device. Four additional Göttingen minipigs were given Hanks’ Balanced Salt Solution and acted as the control group.

RESULTS

Cell survival and no evidence of histological damage, abnormal inflammation, microbiological or immunological abnormalities, tumor formation, or unexpected morbidity or mortality were demonstrated.

CONCLUSIONS

These data strongly support the safety of intraparenchymal injection of LCTOPC1 into the spinal cord using a model anatomically similar to that of the human spinal cord. Furthermore, this research provides guidance for future clinical interventions, including mechanisms for precise positioning and anticipated volumes of biological payloads that can be safely delivered directly into uninjured portions of the spinal cord.

ABBREVIATIONS

gDNA = genomic DNA; HBSS = Hanks’ Balanced Salt Solution; ISH = in situ hybridization; OPC = oligodendrocyte progenitor cell; qPCR = quantitative polymerase chain reaction; SCI = spinal cord injury; VAP = vascular access port.

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Contributor Notes

Correspondence Richard G. Fessler: Rush University Medical Center, Chicago, IL. rfessler@rush.edu.

INCLUDE WHEN CITING Published online July 9, 2021; DOI: 10.3171/2020.12.SPINE201853.

Disclosures Dr. Lebkowski: employed by Geron, Inc. at the time of the study; and employee of Astrias Biotherapeutics. Dr. Priest: employed by Geron, Inc. at the time of the study and Neurona Therapuetics. Dr. Wirth: employed by Geron, Inc. and Lineage Cell Therapeutics at the time of the study.

  • 1

    Anderson KD, Fridén J, Lieber RL. Acceptable benefits and risks associated with surgically improving arm function in individuals living with cervical spinal cord injury. Spinal Cord. 2009;47(4):334338.

    • Search Google Scholar
    • Export Citation
  • 2

    Almad A, Sahinkaya FR, McTigue DM. Oligodendrocyte fate after spinal cord injury. Neurotherapeutics. 2011;8(2):262273.

  • 3

    Hu R, Zhou J, Luo C, et al. . Glial scar and neuroregeneration: histological, functional, and magnetic resonance imaging analysis in chronic spinal cord injury. J Neurosurg Spine. 2010;13(2):169180.

    • Search Google Scholar
    • Export Citation
  • 4

    Scheff SW, Rabchevsky AG, Fugaccia I, et al. . Experimental modeling of spinal cord injury: characterization of a force-defined injury device. J Neurotrauma. 2003;20(2):179193.

    • Search Google Scholar
    • Export Citation
  • 5

    Patel SP, Smith TD, VanRooyen JL, et al. . Serial diffusion tensor imaging in vivo predicts long-term functional recovery and histopathology in rats following different severities of spinal cord injury. J Neurotrauma. 2016;33(10):917928.

    • Search Google Scholar
    • Export Citation
  • 6

    Ek CJ, Habgood MD, Callaway JK, et al. . Spatio-temporal progression of grey and white matter damage following contusion injury in rat spinal cord. PLoS One. 2010;5(8):e12021.

    • Search Google Scholar
    • Export Citation
  • 7

    Priest CA, Manley NC, Denham J, et al. . Preclinical safety of human embryonic stem cell-derived oligodendrocyte progenitors supporting clinical trials in spinal cord injury. Regen Med. 2015;10(8):939958.

    • Search Google Scholar
    • Export Citation
  • 8

    Manley NC, Priest CA, Denham J, et al. . Human embryonic stem cell-derived oligodendrocyte progenitor cells: preclinical efficacy and safety in cervical spinal cord injury. Stem Cells Transl Med. 2017;6(10):19171929.

    • Search Google Scholar
    • Export Citation
  • 9

    Nistor GI, Totoiu MO, Haque N, et al. . Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia. 2005;49(3):385396.

    • Search Google Scholar
    • Export Citation
  • 10

    Keirstead HS, Nistor G, Bernal G, et al. . Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci. 2005;25(19):46944705.

    • Search Google Scholar
    • Export Citation
  • 11

    Zhang YW, Denham J, Thies RS. Oligodendrocyte progenitor cells derived from human embryonic stem cells express neurotrophic factors. Stem Cells Dev. 2006;15(6):943952.

    • Search Google Scholar
    • Export Citation
  • 12

    Amariglio N, Hirshberg A, Scheithauer BW, et al. . Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med. 2009;6(2):e1000029.

    • Search Google Scholar
    • Export Citation
  • 13

    Santamaría AJ, Solano JP, Benavides FD, Guest JD. Intraspinal delivery of Schwann cells for spinal cord injury. In: Monje PV, Kim HA, eds.Schwann Cells: Methods and Protocols, Methods in Molecular Biology. Vol 1739. Springer Science+Business Media, LLC;2018:467484.

    • Search Google Scholar
    • Export Citation

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