Human Glial Progenitor Cells Effectively Remyelinate the Demyelinated Adult Brain.

Area of Science:

• Neuroscience
• Cell Biology
• Regenerative Medicine

Background:

• Neonatal transplantation of human glial progenitor cells (hGPCs) successfully remyelinates the brains of young myelin-deficient shiverer mice.
• The efficacy of hGPCs in remyelinating the diffusely demyelinated adult central nervous system (CNS) remained largely uninvestigated.

Purpose of the Study:

• To determine if hGPCs can remyelinate both congenitally hypomyelinated adult shiverer mice and normal adult mice subjected to cuprizone-induced demyelination.
• To assess the functional recovery and cellular behavior of transplanted hGPCs in adult demyelinated CNS environments.

Main Methods:

• Subcortical injection of hGPCs into adult shiverer mice and adult mice undergoing cuprizone-induced demyelination.
• Assessment of remyelination, oligodendrocyte differentiation, and host nervous system function (callosal conduction, ambulation).
• RNA sequencing (RNA-seq) analysis of transplanted hGPCs to understand their transcriptional state post-transplantation.

Main Results:

• In adult shiverers, hGPCs dispersed widely, differentiated into myelinating oligodendrocytes, and improved host callosal conduction and ambulation.
• hGPCs successfully remyelinated denuded axons in cuprizone-demyelinated brains, irrespective of delivery timing (pre- or post-demyelination).
• RNA-seq revealed transcriptional activation of oligodendrocyte differentiation programs in hGPCs from demyelinated brains, distinct from those not exposed to demyelination.

Conclusions:

• Transplanted hGPCs can disperse throughout the adult CNS and broadly myelinate regions of dysmyelination.
• hGPCs can be recruited as myelinogenic oligodendrocytes in adult life in response to demyelination.
• These findings support the potential of hGPC transplantation for treating adult CNS demyelinating disorders.