Transplanted human glial-restricted progenitors can rescue the survival of dysmyelinated mice independent of the production of mature, compact myelin

Agatha Lyczek, Antje Arnold, Jiangyang Zhang, James T. Campanelli, Miroslaw Janowski, Jeff W Bulte, Piotr Walczak

Research output: Contribution to journalArticle

Abstract

The therapeutic effect of glial progenitor transplantation in diseases of dysmyelination is currently attributed to the formation of new myelin. Using magnetic resonance imaging (MRI), we show that the therapeutic outcome in dysmyelinated shiverer mice is dependent on the extent of cell migration but not the presence of mature and compact myelin. Human or mouse glial restricted progenitors (GRPs) were transplanted into rag2−/ shiverer mouse neonates and followed for over one year. Mouse GRPs produced mature myelin as detected with multi-parametric MRI, but showed limited migration without extended animal lifespan. In sharp contrast, human GRPs migrated extensively and significantly increased animal survival, but production of mature myelin did not occur until 46 weeks post-grafting. We conclude that human GRPs can extend the survival of transplanted shiverer mice prior to production of mature myelin, while mouse GRPs fail to extend animal survival despite the early presence of mature myelin. This paradox suggests that transplanted GRPs provide therapeutic benefits through biological processes other than the formation of mature myelin capable to foster rapid nerve conduction, challenging the current dogma of the primary role of myelination in regaining function of the central nervous system.

Original languageEnglish (US)
Pages (from-to)74-86
Number of pages13
JournalExperimental Neurology
Volume291
DOIs
StatePublished - May 1 2017

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Myelin Sheath
Neuroglia
Survival
Magnetic Resonance Imaging
Biological Phenomena
Neural Conduction
Therapeutic Uses
Cell Movement
Central Nervous System
Transplantation
Therapeutics

Keywords

  • Glial progenitors
  • MRI
  • Myelin
  • Shiverer
  • Transplantation

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Transplanted human glial-restricted progenitors can rescue the survival of dysmyelinated mice independent of the production of mature, compact myelin. / Lyczek, Agatha; Arnold, Antje; Zhang, Jiangyang; Campanelli, James T.; Janowski, Miroslaw; Bulte, Jeff W; Walczak, Piotr.

In: Experimental Neurology, Vol. 291, 01.05.2017, p. 74-86.

Research output: Contribution to journalArticle

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