Modified bone marrow cells
Posted: Tue Apr 10, 2007 11:09 am
Hi everyone,
We know that inflammation is a key part of the recovery and repair strategy of the CNS, now we have a protein, (TREM-2), which appears to play a vital role in this. Not only does it trigger macrophages, (white blood cells), to engulf and destroy all the dead bits of myelin which are hanging around after damage has occurred, but it then calms down the inflammation which, if it lasts too long, can itself begin to cause damage.
There is a suspicion that a major difference, (perhaps the only one), between relapsing MS and progressive, is that if you have a remission it occurs during this repair period -- in those lucky enough to have a "better" immune response.
I wondered if levels of TREM-2 could account for different types of MS... those with average levels don't get MS at all because the protein triggers the normal amount of repair and maintenance which should be going on all the time; slightly low, and you get some repair but not quite enough to recover from every attack, (RRMS); very low, and the deterioration is almost constant, (PPMS).
The good news is, bone-marrow cells are easy to get hold of, and migrate from the bloodstream during an attack.
Dom.
Public release date: 9-Apr-2007
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Contact: Andrew Hyde
press@plos.org
44-122-346-3330
Public Library of Science
Modified bone marrow cells can help recovery in an animal model of multiple sclerosis
A new study published in PLoS Medicine has shown that modified bone marrow cells can help recovery in an animal model of multiple sclerosis (MS). Harald Neumann and colleagues from the University of Bonn modified myeloid precursor cells to express a protein (triggering receptor expressed on myeloid cells-2 (TREM2), which is normally made by microglia - a cell from the nervous system - and injected these TREM2-expressing cells into the veins of mice with experimental autoimmune encephalomyelitis (EAE, an animal model of MS).
The researchers examined the migration of these cells into the spinal cord of the mice, their effect on the symptoms of EAE, and what effect there was on the clearance of cell debris and inflammatory responses in the spinal cord of the mice. They found that neither TREM2-expressing nor control myeloid precursor cells migrated into the spinal cord when injected into healthy mice or into animals just beginning to show the symptoms of EAE. However, both control and modified cells migrated into the spinal cord when injected into animals when EAE symptoms were at their peak. The injection of TREM2-expressing myeloid precursor cells (but not control myeloid precursor cells) at this time reduced EAE symptoms and nerve damage, and halted loss of myelin and also increased the clearance of cell debris and myelin fragments.
These findings will need to be repeated in further animal models before the implications for human disease are clear; however, they open up an avenue of further research.
###
Citation: Takahashi K, Prinz M, Stagi M, Chechneva O, Neumann H (2007) TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis. PLoS Med 4(4): e124.
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://medicine.plosjournals.org/perlse ... ed.0040124
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-04-04-neumann.pdf
Related image for press use: http://www.plos.org/press/plme-04-04-neumann.jpg
- Caption: TREM2-transduced myeloid precursors (green) facilitating tissue debris clearance in an inflammatory spinal cord lesion of experimental autoimmune encephalomyelitis
CONTACT:
Harald Neumann
Institute of Reconstructive Neurobiology/ Uni Bonn
Neural Regeneration
Sigmund-Freud-Str. 25
Bonn, NRW 53127
Germany
+49.228.6885.541
hneuman1@uni-bonn.de
About PLoS Medicine:
PLoS Medicine is an open access, freely available international medical journal. It publishes original research that enhances our understanding of human health and disease, together with commentary and analysis of important global health issues. For more information, visit http://www.plosmedicine.org
About the Public Library of Science:
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org
--------------------------------------------------------------------------------
[ Print Article | E-mail Article | Close Window ]
We know that inflammation is a key part of the recovery and repair strategy of the CNS, now we have a protein, (TREM-2), which appears to play a vital role in this. Not only does it trigger macrophages, (white blood cells), to engulf and destroy all the dead bits of myelin which are hanging around after damage has occurred, but it then calms down the inflammation which, if it lasts too long, can itself begin to cause damage.
There is a suspicion that a major difference, (perhaps the only one), between relapsing MS and progressive, is that if you have a remission it occurs during this repair period -- in those lucky enough to have a "better" immune response.
I wondered if levels of TREM-2 could account for different types of MS... those with average levels don't get MS at all because the protein triggers the normal amount of repair and maintenance which should be going on all the time; slightly low, and you get some repair but not quite enough to recover from every attack, (RRMS); very low, and the deterioration is almost constant, (PPMS).
The good news is, bone-marrow cells are easy to get hold of, and migrate from the bloodstream during an attack.
Dom.
Public release date: 9-Apr-2007
[ Print Article | E-mail Article | Close Window ]
Contact: Andrew Hyde
press@plos.org
44-122-346-3330
Public Library of Science
Modified bone marrow cells can help recovery in an animal model of multiple sclerosis
A new study published in PLoS Medicine has shown that modified bone marrow cells can help recovery in an animal model of multiple sclerosis (MS). Harald Neumann and colleagues from the University of Bonn modified myeloid precursor cells to express a protein (triggering receptor expressed on myeloid cells-2 (TREM2), which is normally made by microglia - a cell from the nervous system - and injected these TREM2-expressing cells into the veins of mice with experimental autoimmune encephalomyelitis (EAE, an animal model of MS).
The researchers examined the migration of these cells into the spinal cord of the mice, their effect on the symptoms of EAE, and what effect there was on the clearance of cell debris and inflammatory responses in the spinal cord of the mice. They found that neither TREM2-expressing nor control myeloid precursor cells migrated into the spinal cord when injected into healthy mice or into animals just beginning to show the symptoms of EAE. However, both control and modified cells migrated into the spinal cord when injected into animals when EAE symptoms were at their peak. The injection of TREM2-expressing myeloid precursor cells (but not control myeloid precursor cells) at this time reduced EAE symptoms and nerve damage, and halted loss of myelin and also increased the clearance of cell debris and myelin fragments.
These findings will need to be repeated in further animal models before the implications for human disease are clear; however, they open up an avenue of further research.
###
Citation: Takahashi K, Prinz M, Stagi M, Chechneva O, Neumann H (2007) TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis. PLoS Med 4(4): e124.
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://medicine.plosjournals.org/perlse ... ed.0040124
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-04-04-neumann.pdf
Related image for press use: http://www.plos.org/press/plme-04-04-neumann.jpg
- Caption: TREM2-transduced myeloid precursors (green) facilitating tissue debris clearance in an inflammatory spinal cord lesion of experimental autoimmune encephalomyelitis
CONTACT:
Harald Neumann
Institute of Reconstructive Neurobiology/ Uni Bonn
Neural Regeneration
Sigmund-Freud-Str. 25
Bonn, NRW 53127
Germany
+49.228.6885.541
hneuman1@uni-bonn.de
About PLoS Medicine:
PLoS Medicine is an open access, freely available international medical journal. It publishes original research that enhances our understanding of human health and disease, together with commentary and analysis of important global health issues. For more information, visit http://www.plosmedicine.org
About the Public Library of Science:
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org
--------------------------------------------------------------------------------
[ Print Article | E-mail Article | Close Window ]