Dystrophic epidermolysis bullosa. (DEB) is an often fatal skin dis- order caused by a mutation in the type VII collagen gene. Patients suf- fer from a lack of the ...
RESEARCH UPDATE
doi:10.1006/mthe.2002.0823
Priming Neural Stem Cells for a Cholinergic Future
A
n exciting therapeutic strategy for neurodegenerative disorders
heparin and laminin. A subset of cells responded by developing a phenotype reminiscent of cholinergic neurons in vitro. More importantly, nearly 95% of the primed cells grafted into diverse regions of the brain developed into region-specific neuronal subtypes. In particular, when delivered to certain regions of the brain that normally contain cholinergic neurons, such as the spinal cord or medial septum, the primed cells developed into cholinergic-like neurons, whereas unprimed cells appeared to become astrocytes. The next step is to determine the nature of the regionspecific cues working on these primed stem cells after grafting. Nature Neuroscience, doi:10.1038/nn974
Cholinergic neurons from primed fetal human neural stem cells (hNSCs) in the medial septum of adult rats. Courtesy Ping Wu.
and injuries is the replacement of dying or dysfunctional neurons with those generated from neural stem cells (NSCs) in vitro. A problem with this approach is that most stem cells do not become neurons when grafted into certain non-neurogenic regions of the adult brain. In the December 2002 issue of Nature Neuroscience, Ping Wu and colleagues provide new data that suggests that one way to get around this problem is to first ‘prime’ the NSCs by incubating them in a cocktail of trophic factors prior to delivery into the adult CNS. The authors of the new study wanted to create cholinergic neurons—neurons that could potentially be used to replace motor neurons lost in Lou Gehrig’s disease or spinal cord injury. They took NSCs isolated originally from the cortex of a human fetus and grown several generations in culture, and treated them with bFGF,
ystrophic epidermolysis bullosa (DEB) is an often fatal skin dis-
to its epidermis, resulting in scarring and cancer. In the December 2002 issue of Nature Genetics, David Woodley and colleagues use a combination of gene therapy and tissue engineering to treat a mouse model of the disease. The authors first expressed a normal copy of the collagen gene in human skin cells, using a stateof-the-art lentiviral vector. The gene-corrected keratinocytes and fibroblasts synthesized and secreted the collagen, and reverted to normal morphology and function. The authors then showed that they could generate human skin on immunodeficient mice. They introduced a ‘slurry’ of the engineered cells into an inert silicone chamber on the denuded skin of SCID mice. Only the genetically altered cells were able to generate an epidermis and dermis with normal connections. As skin is a renewable tissue that undergoes constant regeneration, the next step will be to determine whether a similar approach will work in keratinocyte stem cells. If successful, it could provide the blueprint for a therapeutic strategy in DEB patients.
Immunofluorescence of collegen in mutant (left) and gene-corrected (right) skin. Copyright, Nature Genetics.
order caused by a mutation in the type VII collagen gene. Patients suffer from a lack of the anchoring fibrils that attach the skin’s dermis
