Rats with brain damage have had some of their memory capacity restored after being injected with cells derived from embryonic stem cells. The study focused on the damage caused by radiation, but wider applications may follow.
“Radiation therapy to the brain is a powerful tool in the management of many cancers,” note a team led by Dr. Viviane Tabar of the Memorial Sloan Kettering Cancer Center in Cell Stem Cell. However, the damage can be severe and untreatable. “As we get better at treating some cancers and our patients live longer, it’s becoming increasingly obvious that many of them suffer from long-term quality-of-life issues."
The authors refer to symptoms including, “Progressive impairments in memory, attention, executive function, and motor coordination...as well as learning difficulties and a decrease in intelligence quotients (IQ) in children.” While the brain may find ways to work around some of the damage so that symptoms ease with time, others never heal.
One problem is the widespread destruction of progenitors for brain cells called oligodendrocytes. Oligodendrocytes wrap the nerve fibers that transmit electrical messages within the brain and central nervous system in insulating myelin. Without them, the fibers demyelininate and signal transmission becomes erratic.
Credit: Designua/Shutterstock. A single oligodendrocyte can coat many nerve fibers with myelin.
The researchers found similar effects on rat brains when given clinical levels of radiation. More significantly, they demonstrated that these could be reversed using oligodendrocyte progenitors produced from embryonic stem cells. Following previous work by Tabar, the treatment used human—rather than rodent—stem cells, making the step to clinical application shorter than might otherwise be the case.
Injections took place four weeks after the rats were irradiated. The cells were subsequently found to be widely incorporated into the rats' brains and myelination returned to near normal levels. Moreover, the rodents showed “significant improvements” in memory, which was defined as showing more interest in an object they had not seen before compared with one they had. On the other hand, the motor balance and coordination of the group treated in this way showed no improvement.
The experiment was repeated, but this time injecting the cells into two sites in the rats' brains rather than one. Rats that received cells in both the cerebellum and the corpus callosum improved on both tests. None of the rats showed evidence of side effects, such as tumors formed from the injected cells, which has sometimes occurred in the past.
In vitro differentiation of stem cells into neurons has been achieved for some time now, but oligodendrocytes have proven more difficult than other brain cells, which the authors attribute to their “protracted developmental timeline” when forming prior to birth.