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Biotechnology, Health and Business in Canada, the United States and Worldwide

Friday Science Review: November 18, 2011

NF-κβ1 Restrains Maturation of Dendritic Cells

Ontario Cancer Institute ♦ University of Toronto

Published in Nature Medicine, November 13, 2011

Dendritic cells (DCs) are critical for adaptive immune response, however if their proliferation becomes overzealous or their survival too prolonged they can cause autoimmunity. While most researchers have focused on the factors that stimulate DC maturation and autoimmunity, a group at the Ontario Cancer Institute has taken a different approach, and begged the question as to whether there exist factors that put a damper on DC maturation. Sure enough they recently discovered that NF-κβ1 maintains the resting state of DCs. Unstimulated DCs derived from mice lacking the Nfkb1 gene were able to activate CD8+ T lymphocytes. Injecting Nfkb1-/- DCs into mice could also produce diabetes, an autoimmune disease wherein the host’s immune system slowly eats away at insulin producing cells in the pancreas. NF-κβ1 ensures that DC production of TNF-α is regulated. Without NF-κβ1 the production of TNF-α becomes dysregulated leading to upregulation of granzyme B in T cells, which causes autoimmunity.

Human Spinal Cord-Derived NSPCs Survive Transplantation and Differentiate

Toronto Western Research Institute and Krembil Neuroscience Centre

Published in PLoS ONE, November 2, 2011

Researchers have provided a proof-of-principle that adult neural stem/progenitor cells (NSPCs) from the human spinal column can be successfully transplanted in a spinal cord injury (SCI) setting. The ability of NSPCs to engraft and differentiate in vivo was assessed with a mouse model of SCI. Following transplantation NSPCs differentiated into both neurons and glia. In order to establish NSPC lines, neural tissue samples were taken from the spine of organ transplant donors and grown in an adherent cell culture. NSPCs were selected and expanded in the presence of epidermal growth factor and fibroblast growth factor-2. Cultures can be maintained for at least 9 months and exhibit full multipotentiality in that they can differentiate into all three neural cells types, including neurons, oligodendrocytes, and astrocytes. In 2008, a research group successfully established an NSPC cell line, however was not able to scale the cells up for experimentation. This study is the first that shows NSPCs derived from the human spinal column can be scaled up for therapeutic purposes.

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