Transplanted Human Glial-Restricted Progenitors Can Rescue the Survival of Dysmyelinated Mice Independent of the Production of Mature, Compact Myelin
| Autor: | Jiangyang Zhang, James T. Campanelli, Jeff W.M. Bulte, Antje Arnold, Piotr Walczak, Agatha Lyczek, Miroslaw Janowski |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Time Factors Cell Survival Mice Transgenic Nerve Tissue Proteins Article 03 medical and health sciences Myelin Mice 0302 clinical medicine Developmental Neuroscience Compact myelin Cell Movement Tubulin Gangliosides Glial Fibrillary Acidic Protein medicine Basic Helix-Loop-Helix Transcription Factors Animals Humans Progenitor cell Myelin Proteolipid Protein Myelin Sheath Glial fibrillary acidic protein biology fungi Brain Cell Differentiation Myelin Basic Protein Oligodendrocyte Transcription Factor 2 Myelin basic protein Myelin proteolipid protein Transplantation DNA-Binding Proteins Disease Models Animal 030104 developmental biology medicine.anatomical_structure Neurology nervous system Spinal Cord biology.protein Neuroglia Neuroscience 030217 neurology & neurosurgery Demyelinating Diseases Stem Cell Transplantation |
| Popis: | 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 46weeks 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. |
| Databáze: | OpenAIRE |
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