01 January 2003
Lancet Neurology, Volume 2, Number 1
By use of a novel in vitro priming procedure, researchers at the University of Texas Medical Branch at Galveston have been able to obtain an almost pure neuronal population after grafting human neural stem cells (hNSCs) into both neurogenic and non-neurogenic areas of the adult rat CNS. Undifferentiated hNSCs usually differentiate into glial cells, rather than neurons, when grafted into non-neurogenic areas. “These primed cells become specific types of neurons, including cholinergic neurons, according to where they are injected”, explains Ping Wu, the team leader. Clive Svendsen (Waisman Center, Madison, WI, USA) comments: “if this transplant data can be reliably produced by other laboratories we are one step closer to providing neurons on demand from human neural progenitor cells”.
Wu and co-workers carried out preliminary experiments in vitro with hNSCs derived from 8 to 10-week-old human fetuses. They identified a priming “cocktail” of basic fibroblast growth factor, heparin, and laminin; after exposure to this cocktail for 6 days, the cells differentiated into cholinergic neurons. The researchers then investigated the effect of this priming procedure on hNSCs grafted into four areas of the adult-rat nervous system: prefrontal cortex, medial septum, hippocampus, and the spinal cord (Nat Neurosci 2002; 5: 1271–78).
By transfection of hNSCs with enhanced green fluorescent protein before grafting, the researchers were able to identify the grafted cells in the brain of the host rat. Primed hNSCs grafted into the hippocampus, a neurogenic area of the brain, developed characteristics typical of pyramidal neurons: about 70% of primed hNSCs grafted into the CA1 became GABAergic. In contrast, primed hNSCs grafted into the medial septum or spinal cord became cholinergic (about 60% and 55%, respectively). Some of the cells in the spinal cord became glutamatergic (14%), as did those that were grafted into the prefrontal cortex (50%).
The authors hope that we are one step closer to the development of stem
cell-based therapies for neurotrauma and neurodegenerative diseases. However,
Alberto Martinez-Serrano (Autonomous University of Madrid, Spain) cautions
“it is far from clear that other preparations of hNSCs would behave similarly,
and therefore one should wait to see whether these results are reproducible
or whether they are particular to this cell preparation”. Lukas Sommer
(Swiss Federal Institute of Technology, Zurich, Switzerland) echoes these
concerns and adds “it will be important to address whether the newly formed
neurons functionally integrate in neuronal circuits and whether such integration
leads to functional recovery in disease model systems”.
© Copyright 2003, Lancet Neurology