Does the preclinical evidence for functional remyelination following myelinating cell engraftment into the injured spinal cord support progression to clinical trials?

Abstract

This article reviews all historical literature in which rodent-derived myelinating cells have been engrafted into the contused adult rodent spinal cord. From 2,500 initial PubMed citations identified, human cells grafts, bone mesenchymal stem cells, olfactory ensheathing cells, non-myelinating cell grafts, and rodent grafts into hemisection or transection models were excluded, resulting in the 67 studies encompassed in this review. Forty five of those involved central nervous system (CNS)-derived cells, including neural stem progenitor cells (NSPCs), neural restricted precursor cells (NRPs) or oligodendrocyte precursor cells (OPCs), and 22 studies involved Schwann cells (SC). Of the NSPC/NPC/OPC grafts, there was no consistency with respect to the types of cells grafted and/or the additional growth factors or cells co-grafted. Enhanced functional recovery was reported in 31/45 studies, but only 20 of those had appropriate controls making conclusive interpretation of the remaining studies impossible. Of those 20, 19 were properly powered and utilized appropriate statistical analyses. Ten of those 19 studies reported the presence of graft-derived myelin, 3 reported evidence of endogenous remyelination or myelin sparing, and 2 reported both. For the SC grafts, 16/21 reported functional improvement, with 11 having appropriate cellular controls and 9/11 using proper statistical analyses. Of those 9, increased myelin was reported in 6 studies. The lack of consistency and replication among these preclinical studies are discussed with respect to the progression of myelinating cell transplantation therapies into the clinic.

The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury

“…The transplantation of cells into the injured spinal cord with the aim of producing new oligodendrocytes or Schwann cells has been frequently pursued to improve remyelination, and is the topic of several thorough reviews (Assinck, Duncan, Hilton, et al, 2017;Kanno, Pearse, Ozawa, Itoi, & Bunge, 2015;Myers et al, 2016). Transplanted cells will be in competition with endogenous OPC-derived remyelinating cells, which are capable of efficient, if somewhat delayed, remyelination.…”

“…Many of these surviving axons are stripped of their myelin (demyelinated; Bunge, Puckett, Becerra, Marcillo, & Quencer, ; Guest, Hiester, & Bunge, ; Norenberg et al, ) likely due to the loss of oligodendrocytes. Accordingly, many have hypothesized that myelin regeneration is a plausible therapeutic target to promote signal conduction and protect axons from secondary damage (Alizadeh, Dyck, & Karimi‐Abdolrezaee, ; Myers, Bankston, Burke, Ohri, & Whittemore, ; Papastefanaki & Matsas, ; Plemel et al, ). However, there is no direct evidence that oligodendrocyte remyelination contributes to the partial spontaneous functional recovery after SCI.…”

Sudan black: a fast, easy and non‐toxic method to assess myelin repair in demyelinating diseases

“…Moreover, sudan black staining enables the visualization of the tissue structure including demyelinated axons (Figure c ) which is not the case for MBP immunostaining. Of note here is also that the auto‐ and background‐fluorescence quenching properties of sudan black which lead to an accentuation of fluorescent signal from structures outside of the myelin sheaths (Figure b ).…”

The influence of neurotransplantation with different allogenic tissues on the course of the spasticity and chronic pain syndrome after experimental spinal cord injury

“…Попри цей оче-видний факт, вивчення впливу таких втручань при спінальній травмі на перебіг синдрому спастичності [28,29] та хронічного больового синдрому [30][31][32][33][34][35][36][37][38][39][40] становить міноритарну частку робіт, присвячених темі відновного лікування спінальної травми. Крім того, очевидним є факт обмеження сучасних нейроінженер-них втручань при спінальній травмі [41][42][43][44]; відсутній порівняльний аналіз їх ефективності на тлі тканинної нейротрансплантації, передусім тих її варіантів, що оперують найбільш місткими джерелами потенційних учасників нейропластичного процесу. З позиції сучас-ної ембріології такими джерелами є:…”