Radiotherapy is an important and effective tool in the war against cancer, but its use for treating brain tumors brings with it unwanted side effects that can cause long term suffering to the patient. Radiation induces the depletion of oligodendrocyte progenitor cells (OPCs) which leads to the loss of the protective myelin sheath that covers neural cell axons causing cognitive decline and motor coordination impairment.
Up until now, there have been no successful treatments for these side effects, but researchers from the group of Viviane Tabar (Memorial Sloan Kettering Cancer) hope to change that. They have optimized a differentiation strategy for the production of replacement OPCs from human pluripotent stem cells (hPSCs) and show that upon transplantation into a rat model these OPCs have myelination capabilities that can reverse radiation induced side effects.
Piao and Major et al show that:
- A clinical dose of radiation given to rats induced the loss of OPCs, loss of myelination, loss of brain volume, and a reduction in cognitive and memory test performance.
- Human oligodendrocyte progenitors (hOPCs) can be efficiently derived and isolated from human embryonic stem cells and induced pluripotent stem cells.
- Oligodendrocytes produced from these cells all have the ability to efficiently myelinate axons in vitro.
- After grafting hOPCs into the forebrain, extensive remyelination in the brain occurs, leading to improved performance in tasks reflecting multiple cognitive processes related to memory and learning.
- Motor co-ordination improved after hOPC grafting into the cerebellum.
This is very welcome news to researchers, clinicians, and patients alike. A new protocol for the production of vast amounts of safe, clinically relevant patient-specific cells and a strategy to improve quality of life among cancer survivors has these researchers looking to the future. Not only do they hope for the implementation of a clinical trial and hopefully a first viable therapeutic option for radiotherapy-related side effects, but they also foresee the adaptation of their work into other fields where demyelination plays a major role in disease pathogenesis.
Read this encouraging study in Cell Stem Cell, January 2015.