Neuroscientists at the University of Florida’s McKnight Brain Institute have discovered that glial cells isolated from the brains of adult humans can generate multipotent neural progenitors.
Astroglial cells were obtained from gray matter in multiple forebrain regions of patients undergoing surgery for the treatment of epilepsy, then cultured in a medium containing epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF).
There appeared to be no difference between progenitors derived from astrocytes in the temporal cortex and those derived from cells in the hippocampus. The progenitors obtained re-entered the cell cycle, and the homogenous population was found to be highly expandable. Remarkably, the researchers estimate that a single progenitor can generate enough neurons for 40 million adult human brains (that is, 10 quadrillion cells – don’t ask me how they did the calculations!)
In culture, the cells adopted a hybrid morphology, expressing molecular markers for both astrocytes and immature neurons and glia while retaining the appearance of astroglial cells. Electrophysiological studies showed that the cells also had prominent sodium and potassium channel activity.
The progenitor cell line derived from the astroglia was successfully maintained for nearly a year, without showing any signs of ageing or mutations that could make the cells cancerous. Cultured cells were successfully transfected with lentiviral vectors carrying the gene encoding green fluorescent protein (GFP), and stably transfected cells continued to express GFP in culture three days after transfection.
When injected into the lateral ventricles of newborn mice, the cells were effectively incorporated into the brain of the host mice, where they adopted the phenotypes of astroglial cells and, less frequently, of mature neurons. Cells continued to express GFP more than 30 days after being injected into the lateral ventricles.
In contrast, cells grafted directly into the cortex of adult mice adopted neuronal morphologies, extended processes and expressed neuronal markers. There was limited migration into adjacent brain regions; some of the cells were found in the CA1 and CA3 regions of the hippocampus, and displayed characteristics of endogenous pyramidal cells (left).
Apart from demonstrating glia-to-neuron transdifferentiation, via undifferentiated, multipotent progenitors, the work provides evidence that neural progenitors are present in broadly distributed populations in the human brain.
It is possible, however, that existing neural progenitors were removed along with astrocytes from the brains of the patients, but Steindler prefers to think that the isolated astrocytes somehow de-differentiated to generate the neural progenitors.
The apparent plasticity of the neural progenitors, the ability of the cell population to expand dramatically, and their amenablilty to genetic modification and transplantation, shows huge potenital for the development of therapies for neurodegenerative.
“This is a completely new source of human brain cells that can potentially be used to fight Parkinson’s disease, Alzheimer’s disease, stroke and a host of other brain disorders,” says Dennis Steindler, who led the work, which is published in Development.