Stem cell enhancement
"People are excited about the potential of stem cells, but most approaches are not leveraging them to their maximum potential," says Madhusudan Peshwa of MaxCyte in Gaithersburg, Maryland. "We're not getting into the driving seat and getting the cells to do what we want them to do."
Many teams have attempted to use adult stem cells in regenerative medicine - to repair damaged tissue after a heart attack, for example -but their efforts have been hampered by problems such as cells dying before reaching their target or not differentiating into the correct cell type.
Now researchers are waking up to the idea of genetically modifying stem cells to enhance their natural attributes and gain a new level of control over them. In the case of heart attacks, stem cells from both skeletal muscle and bone marrow have been shown to repair tissue damage to some degree, either through differentiating into heart muscle cells or releasing chemicals that stimulate existing cells to repair the damage. To make this process more effective, Marc Penn at the Center for Stem Cell and Regenerative Medicine in Cleveland, Ohio, genetically engineered bone marrow stem cells to produce triple the normal amount of a signalling factor called SDF-1. This is an "SOS signal" also released by damaged heart cells after an attack and is thought to recruit repair cells to the damaged area.
"The idea is to try and restart natural signals that initiate repair," says Penn. When the cells were injected into rats' hearts after a heart attack, the team saw a 70 per cent reduction in heart cell death, compared with rats given unmodified stem cells (The FASEB Journal, DOI: 10.1096/fj.06-6558com).
Meanwhile, Duncan Stewart at the University of Toronto, Canada, is focusing on a more differentiated group of cells called endothelial progenitor cells (EPCs), to develop a therapy for pulmonary arterial hypertension (PAH). This is a fatal condition in which tiny blood vessels carrying blood to the lungs are destroyed. Previous studies have shown that EPCs can protect blood vessels against future damage, but Stewart's team wanted EPCs to repair damage to blood vessels after it had occurred.
Endothelial cells usually produce an enzyme called eNOS, which is thought to promote blood vessel growth and protect against cell death. Stewart's team inserted a circular piece of DNA containing the gene for eNOS into EPCs, and then injected the cells into rats with damaged lung vessels. The rats showed a significant improvement in blood flow to the lungs and more survived compared with untreated rats.
"EPCs by themselves seem to have some effect, but you can get much better effects if you push the cells in the right direction," says Stewart, who presented his results at Bio2007 in Boston last month. He has now begun a safety study of eNOS-modified EPCs in 18 humans with PAH.
Linda Geddes
http://www.newscientist.com/article.ns?id=mg19426085
"People are excited about the potential of stem cells, but most approaches are not leveraging them to their maximum potential," says Madhusudan Peshwa of MaxCyte in Gaithersburg, Maryland. "We're not getting into the driving seat and getting the cells to do what we want them to do."
Many teams have attempted to use adult stem cells in regenerative medicine - to repair damaged tissue after a heart attack, for example -but their efforts have been hampered by problems such as cells dying before reaching their target or not differentiating into the correct cell type.
Now researchers are waking up to the idea of genetically modifying stem cells to enhance their natural attributes and gain a new level of control over them. In the case of heart attacks, stem cells from both skeletal muscle and bone marrow have been shown to repair tissue damage to some degree, either through differentiating into heart muscle cells or releasing chemicals that stimulate existing cells to repair the damage. To make this process more effective, Marc Penn at the Center for Stem Cell and Regenerative Medicine in Cleveland, Ohio, genetically engineered bone marrow stem cells to produce triple the normal amount of a signalling factor called SDF-1. This is an "SOS signal" also released by damaged heart cells after an attack and is thought to recruit repair cells to the damaged area.
"The idea is to try and restart natural signals that initiate repair," says Penn. When the cells were injected into rats' hearts after a heart attack, the team saw a 70 per cent reduction in heart cell death, compared with rats given unmodified stem cells (The FASEB Journal, DOI: 10.1096/fj.06-6558com).
Meanwhile, Duncan Stewart at the University of Toronto, Canada, is focusing on a more differentiated group of cells called endothelial progenitor cells (EPCs), to develop a therapy for pulmonary arterial hypertension (PAH). This is a fatal condition in which tiny blood vessels carrying blood to the lungs are destroyed. Previous studies have shown that EPCs can protect blood vessels against future damage, but Stewart's team wanted EPCs to repair damage to blood vessels after it had occurred.
Endothelial cells usually produce an enzyme called eNOS, which is thought to promote blood vessel growth and protect against cell death. Stewart's team inserted a circular piece of DNA containing the gene for eNOS into EPCs, and then injected the cells into rats with damaged lung vessels. The rats showed a significant improvement in blood flow to the lungs and more survived compared with untreated rats.
"EPCs by themselves seem to have some effect, but you can get much better effects if you push the cells in the right direction," says Stewart, who presented his results at Bio2007 in Boston last month. He has now begun a safety study of eNOS-modified EPCs in 18 humans with PAH.
Linda Geddes
http://www.newscientist.com/article.ns?id=mg19426085