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Cell Therapy for Spasticity

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Recovery of function through neuroregeneration is the intent of cell therapy for spinal cord injury with its many secondary health manisfestations including problematic spasticity. Various forms of stem cells have been clinically applied to SCI such as embryonic stem cell derived oligodendrocyte progenitor cells (NCT02302157), neural stem cells (NCT 01321333, 02163876, 01725880, 03069404), and mesenchymal stem cells derived from umbilical cord blood, adipose or bone marrow; protocols can be reviewed at www.clinicaltrials.gov.

To date, safety and feasibility of stem cell administration in human SCI have been reported (Levi et al 2018a and b; Vaquero et al 2018).  Preliminary efficacy, including for spasticity, has also been reported (Levi et al 2018 and Vaquero et al 2018).

Table: Cell Therpy Interventions for Reducing Spasticity
Discussion

Human neural stem cells were surgically implanted in trial participants with chronic (4-24 months post-injury) cervical SCI and assessed for neurological improvement focusing on the UEMS (Upper Extremity Motor Score) of the ISNCSCI (International Standards for Neurological Classification of SCI) and GRASSP (Graded Redefined Assessment of Strength, Sensation and Prehension) measures for upper extremity function. (Levi et al 2018; RCT).  Of the secondary measures in this RCT, the MAS revealed a non-significant decrease in spasticity over 6 months of observation in the treated group.

Similarly, the primary outcome of a pre-post trial for intrathecal administration of autologous mesenchymal stromal cells in chronic (13.65+/-14.79 years post-injury) SCI was the ISNCSCI for sensory and motor improvements and spasticity was assessed secondarily using the Ashworth and Penn scales (Vaquero et al 2018).  No statistical difference was seen in spasticity, pre and post stem cell administration.  However, variable improvement was documented during the trial without persistence of effect to the end of follow-up.

Conclusion

Level 1b evidence (Levi et al 2018; RCT,N=10) has not demonstrated that transplantation of human neural stem cells results in persistent spasticity reduction in participants with chronic cervical SCI.

Level 4 evidence (Vaquero et al 2018; Pre/post, N=11) reveals that initial improvements in spasticity are not persistent as a result of intrathecal administration of autologous mesenchymal stem cells in SCI.

  • Human neural stem cell transplantation in chronic SCI does not reduce spasticity secondary to SCI.

    Intrathecal injection of autologous mesenchymal stem cells in people with chronic SCI is unlikely to result in persistent spasticity reduction