Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Sep;283(Pt B):560-72.
doi: 10.1016/j.expneurol.2016.04.009. Epub 2016 Apr 13.

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

Scott A Myers  1 , Andrew N Bankston  1 , Darlene A Burke  1 , Sujata Saraswat Ohri  1 , Scott R Whittemore  2
Affiliations
Review

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

Scott A Myers et al. Exp Neurol. 2016 Sep.

Abstract

This article reviews all historical literature in which rodent-derived myelinating cells have been engrafted into the contused adult rodent spinal cord. From 2500 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.

Keywords: Neural precursor cells; Neural stem progenitor cells; Oligodendrocytes; Remyelination; Schwann cells; Spinal cord injury; Transplantation.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Venn diagram illustrating the sequential exclusion of CNS-derived myelinating cell transplantation studies using the indicated criteria.
Figure 2
Figure 2
Venn diagram illustrating the sequential exclusion of Schwann cell transplantation studies using the indicated criteria.
See this image and copyright information in PMC

References

    1. Bachelin C, Lachapelle F, Girard C, Moissonnier P, Serguera-Lagache C, Mallet J, Fontaine D, Chojnowski A, Le Guern E, Nait-Oumesmar B, Baron-Van Evercooren A. Efficient myelin repair in the macaque spinal cord by autologous grafts of Schwann cells. Brain. 2005;128:540–549. - PubMed
    1. Bambakidis NC, Miller RH. Transplantation of oligodendrocyte precursors and sonic hedgehog results in improved function and white matter sparing in the spinal cords of adult rats after contusion. Spine J. 2004;4:16–26. - PubMed
    1. Barakat DJ, Gaglani SM, Neravetla SR, Sanchez AR, Andrade CM, Pressman Y, Puzis R, Garg MS, Bunge MB, Pearse DD. Survival, integration, and axon growth support of glia transplanted into the chronically contused spinal cord. Cell Transplant. 2005;14:225–240. - PubMed
    1. Barbour HR, Plant CD, Harvey AR, Plant GW. Tissue sparing, behavioral recovery, supraspinal axonal sparing/regeneration following sub-acute glial transplantation in a model of spinal cord contusion. BMC Neurosci. 2013;14:106. - PMC - PubMed
    1. Barnett SC, Alexander CL, Iwashita Y, Gilson JM, Crowther J, Clark L, Dunn LT, Papanastassiou V, Kennedy PGE, Franklin RJM. Identification of a human olfactory ensheathing cell that can effect transplant-mediated remyelination of demyelinated CNS axons. Brain. 2000;123:1581–1588. - PubMed

Publication types