Elsevier

Mayo Clinic Proceedings

Volume 95, Issue 2, February 2020, Pages 406-414
Mayo Clinic Proceedings

Case report
CELLTOP Clinical Trial: First Report From a Phase 1 Trial of Autologous Adipose Tissue–Derived Mesenchymal Stem Cells in the Treatment of Paralysis Due to Traumatic Spinal Cord Injury

https://doi.org/10.1016/j.mayocp.2019.10.008Get rights and content

Abstract

Spinal cord injury (SCI) is a devastating condition with limited pharmacological treatment options to restore function. Regenerative approaches have recently attracted interest as an adjuvant to current standard of care. Adipose tissue–derived (AD) mesenchymal stem cells (MSCs) represent a readily accessible cell source with high proliferative capacity. The CELLTOP study, an ongoing multidisciplinary phase 1 clinical trial conducted at Mayo Clinic (ClinicalTrials.gov Identifier: NCT03308565), is investigating the safety and efficacy of intrathecal autologous AD-MSCs in patients with blunt, traumatic SCI. In this initial report, we describe the outcome of the first treated patient, a 53-year-old survivor of a surfing accident who sustained a high cervical American Spinal Injury Association Impairment Scale grade A SCI with subsequent neurologic improvement that plateaued within 6 months following injury. Although he improved to an American Spinal Injury Association grade C impairement classification, the individual continued to be wheelchair bound and severely debilitated. After study enrollment, an adipose tissue biopsy was performed and MSCs were isolated, expanded, and cryopreserved. Per protocol, the patient received an intrathecal injection of 100 million autologous AD-MSCs infused after a standard lumbar puncture at the L3-4 level 11 months after the injury. The patient tolerated the procedure well and did not experience any severe adverse events. Clinical signs of efficacy were observed at 3, 6, 12, and 18 months following the injection in both motor and sensory scores based on International Standards for Neurological Classification of Spinal Cord Injury. Thus, in this treated individual with SCI, intrathecal administration of AD-MSCs was feasible and safe and suggested meaningful signs of improved, rather than stabilized, neurologic status warranting further clinical evaluation.

Section snippets

Study Patient

The patient is a 53-year-old male who suffered a surfing accident resulting in a C3-4 SCI. Neurologic examination at the time of the accident revealed complete loss of motor and sensory function below the level of injury along with loss of bowel and bladder sensation. Accordingly, the individual was diagnosed with an American Spinal Injury Association (ASIA) grade A SCI, and underwent a C2-6 posterior cervical decompression and fusion. Postoperatively, improvement in motor and sensory function

Safety and Adverse Events

The patient tolerated the procedure well and did not experience any severe adverse events related to the injection. He reported a mild to moderate headache on day 2, which resolved with acetaminophen. Throughout the 18-month follow-up, no other safety issues or adverse events were reported.

ASIA Motor Score

The total upper extremity motor score progressively improved from 35 at baseline to 44 at 18 months, with more marked improvement on the right (19 at baseline to 25 at 18 months) compared with the left side

Discussion

Spinal cord injury has a complex pathophysiology. One of the more challenging aspects of this life altering pathophysiology is the onset of secondary mechanisms of tissue insult in the subacute and chronic phase following the primary injury. Glial scarring limits axonal regeneration as a complex physicochemical barrier by secreting growth inhibitor molecules. These microenvironmental changes cause the chronically injured spinal cord to be in a refractory state.11 In addition to bridging the

Conclusion

Intrathecal AD-MSC administration may have the potential to improve neurologic function in patients with plateaued clinical improvement following SCI. Further clinical translation of this therapeutic strategy would require demonstration of treatment safety and efficacy in a sufficiently powered randomized controlled trial and identification of prognostic factors predictive of response to intervention.

References (23)

  • Z. Zhou et al.

    Comparison of mesenchymal stromal cells from human bone marrow and adipose tissue for the treatment of spinal cord injury

    Cytotherapy

    (2013)
  • National Spinal Cord Injury Statistical Center. Spinal Cord Injury Facts and Figures at a Glance. NSCISC website,...
  • Spinal cord injury facts and figures at a glance

    J Spinal Cord Med

    (2012)
  • D.P. Lammertse et al.

    Autologous incubated macrophage therapy in acute, complete spinal cord injury: results of the phase 2 randomized controlled multicenter trial

    Spinal Cord

    (2012)
  • N. Evaniew et al.

    Methylprednisolone for the treatment of patients with acute spinal cord injuries: a propensity score-matched cohort study from a Canadian multi-center spinal cord injury registry

    J Neurotrauma

    (2015)
  • S. Casha et al.

    Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury

    Brain

    (2012)
  • N. Evaniew et al.

    Methylprednisolone for the treatment of patients with acute spinal cord injuries: a systematic review and meta-analysis

    J Neurotrauma

    (2016)
  • K.A. Leech et al.

    Effects of serotonergic medications on locomotor performance in humans with incomplete spinal cord injury

    J Neurotrauma

    (2014)
  • A. Norouzi Javidan et al.

    Does consumption of polyunsaturated fatty acids influence on neurorehabilitation in traumatic spinal cord-injured individuals? a double-blinded clinical trial

    Spinal Cord

    (2014)
  • V.R. Dasari et al.

    Mesenchymal stem cells in the treatment of spinal cord injuries: a review

    World J Stem Cells

    (2014)
  • S.K. Oh et al.

    Current concept of stem cell therapy for spinal cord injury: a review

    Korean J Neurotrauma

    (2016)
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    For editorial comment, see page 224

    Grant Support: This work was supported by grants from Regenerative Medicine Minnesota and Mayo Clinic Transform the Practice.

    Potential Competing Interests: Dr Terzic is a member of the board for Rion, LLC. The other authors report no competing interests.

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