EDITOR'S PICK: Repairing spinal cord injury with manipulated neural stem cells
One of the most common causes of disability in young adults is spinal cord injury. Currently, there is no proven reparative treatment. Hope that neural stem cells (NSCs) might be of benefit to individuals with severe spinal cord injury has now been provided by the work of a team of researchers, led by Kinichi Nakashima, at Nara Institute of Science and Technology, Japan, in a mouse model of this devastating condition.
In the study, mice with severe spinal cord injury were transplanted with NSCs and administered a drug known as valproic acid, which is used in the treatment of epilepsy. The valproic acid promoted the transplanted NSCs to generate nerve cells, rather than other brain cell types, and the combination therapy resulted in impressive restoration of hind limb function. The authors hope that this approach, whereby the fate of transplanted NSCs is manipulated, for example by administration of valproic acid, could be developed as an effective treatment for severe spinal cord injury.
In an accompanying commentary, Tamir Ben-Hur, at Hadassah Hebrew University Medical School, Israel, highlights the impressive functional recovery attained using this approach but cautions that further work is needed before it can be determined whether this approach will work in human patients.
TITLE: Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury
AUTHOR CONTACT:
Kinichi Nakashima
Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.
Phone: 81.743.72.5471; Fax: 81.743.72.5479; Email: kin@bs.naist.jp.
View this article at: http://www.jci.org/articles/view/42957?key=078363753b2bb89629a5
ACCOMPANYING COMMENTARY TITLE: Reconstructing neural circuits using transplanted neural stem cells in the injured spinal cord
AUTHOR CONTACT:
Tamir Ben-Hur
Hadassah Hebrew University Medical School, Jerusalem, Israel.
Phone: 972.2.6777741; Fax: 972.2.6437782; E-mail: tamir@hadassah.org.il.
View this article at: http://www.jci.org/articles/view/43575?key=b6af60cb9466d4f392be
PULMONARY: Can vitamin D reduce a complication of cystic fibrosis?
The lungs of most individuals with cystic fibrosis are colonized by the mold Aspergillus fumigatus. In some this causes a condition known as allergic bronchopulmonary aspergillosis (ABPA), which is characterized by wheezing, lung infiltration by immune cells, and lung scarring, while others remain disease free. A team of researchers, led by Jay Kolls, at Louisiana State University Health Sciences Center, New Orleans, has now compared individuals with cystic fibrosis with and without ABPA and identified an immune signature of ABPA. Specifically, individuals with ABPA exhibited heightened immune responses known as CD4+ Th2 responses and lower levels of vitamin D in the blood. As in vitro addition of vitamin D reduced Th2 responses by CD4+ T cells from patients with ABPA, the authors suggest that vitamin D should be tested for its ability to prevent and/or treat ABPA in individuals with cystic fibrosis.
TITLE: Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis
AUTHOR CONTACT:
Jay K. Kolls
Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA. Phone: 504.568.6117; Fax: 504.568.8500; E-mail: jkolls@lsuhsc.edu.
View this article at: http://www.jci.org/articles/view/42388?key=147279a4985d0bf59979
INFLAMMATION: The mechanisms of therapeutic control of sepsis
Sepsis is a life-threatening condition characterized by a whole-body inflammatory response. Patients with the most severe forms of sepsis are treated with a recombinant form of the human protein aPC. However, the mechanisms by which it mediates its beneficial effects in these patients are not completely understood. But now, a team of researchers, led by Hartmut Weiler, at the BloodCenter of Wisconsin, Milwaukee, has found that immune cells known as dendritic cells that express the proteins CD8 and EPCR are required for aPC to reduce mortality in a mouse model of lethal sepsis. As discussed by Wolfram Ruf, at The Scripps Research Institute, La Jolla, in an accompanying commentary, these data jive well with other recent studies to indicate that control of innate immune responses is an important effect of aPC therapy in patients with severe sepsis.
TITLE: Activated protein C targets CD8+ dendritic cells to reduce the mortality of endotoxemia in mice
AUTHOR CONTACT:
Hartmut Weiler
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin, USA.
Phone: 414.937.3813; Fax: 414.937.6284; E-mail: hartmut.weiler@bcw.edu.
View this article at: http://www.jci.org/articles/view/42629?key=86b5a310b28f9354c3a7
ACCOMPANYING COMMENTARY TITLE: New players in the sepsis-protective activated protein C pathway
AUTHOR CONTACT:
Wolfram Ruf
The Scripps Research Institute, La Jolla, California, USA.
Phone: 858.784.2748; Fax: 858.784.848; E-mail: ruf@scripps.edu.
View this article at: http://www.jci.org/articles/view/44266?key=baa49035cc977e44cbea
VASCULAR DISEASE: Keeping genes silent a key to avoiding ANCA disease
One cause of inflammation of the small blood vessels (small-vessel vasculitis) is the presence of antineutrophil cytoplasmic autoantibodies (ANCAs) — immune molecules that target proteins produced by immune cells known as neutrophils and cause neutrophils to attack the walls of small blood vessels. ANCAs only arise when neutrophil proteins are expressed aberrantly. Understanding how neutrophil proteins are aberrantly expressed is key to understanding the disease. Ronald Falk and colleagues, at the University of North Carolina, Chapel Hill, have now provided insight into this by analyzing the genes responsible for generating two of the neutrophil proteins aberrantly expressed in ANCA patients, PR3 and MPO. They found that the PR3 and MPO genes in healthy individuals exhibited modifications consistent with gene silencing and that these modifications were perturbed in individuals with ANCA. They therefore conclude that a lack of gene silencing leads to inappropriate expression of the PR3 and MPO genes in individuals with ANCA.
TITLE: Epigenetic basis for aberrant upregulation of autoantigen genes in humans with ANCA vasculitis
AUTHOR CONTACT:
Ronald J. Falk
UNC–Chapel Hill, Chapel Hill, North Carolina, USA.
Phone: 919.966.2561, ext. 250; Fax: 919.966.4251; E-mail: falkrj@med.unc.edu.
View this article at: http://www.jci.org/articles/view/40034?key=52599c069a0f8e2d8808
Journal
Journal of Clinical Investigation