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MIT: Stem-cell therapies for brain more complicated than thought
November 28, 2007CAMBRIDGE, Mass. - An MIT research team's latest finding suggests that stem cell therapies for the brain could be much more complicated than previously thought.
In a study published in the Public Library of Science (PloS) Biology on Nov. 13, MIT scientists report that adult stem cells produced in the brain are pre-programmed to make only certain kinds of connections-making it impossible for a neural stem cell originating in the brain to be transplanted to the spinal cord, for instance, to take over functions for damaged cells.
Some researchers hope to use adult stem cells produced in the brain to replace neurons lost to damage and diseases such as Alzheimer's. The new study calls this into question.
"It is wishful thinking to hope that adult stem cells will be able to modify themselves so that they can become other types of neurons lost to injury or disease," said Carlos E. Lois, assistant professor of neuroscience in MIT's Picower Institute for Leaning and Memory.
In developing embryos, stem cells give rise to all the different types of cells that make up the body--skin, muscle, nerve, brain, blood and more. Some of these stem cells persist in adults and give rise to new skin cells, stomach lining cells, etc. The idea behind stem-cell therapy is to use these cells to repair tissue or organs ravaged by disease.
To realize this potential, the stem cells have to be "instructed" to become liver cells, heart cells or neurons. The MIT study, which looked only at adult neural stem cells, suggests it will be necessary to learn how to program any kind of stem cell-embryonic, adult or those derived through other means-to produce specific types of functioning neurons. Without this special set of instructions, a young neuron will only connect with the partners for which it was pre-programmed.
The adult brain harbors its own population of stem cells that spawn new neurons for life. The MIT study shows that a neural stem cell is irreversibly committed to produce only one type of neuron with a pre-set pattern of connections. This means that a given neuronal stem cell can have only limited use in replacement therapy.
"A stem cell that produces neurons that could be useful to replace neurons in the cerebral cortex (the type of neurons lost in Alzheimer's disease) will be most likely useless to replace neurons lost in the spinal cord," said Lois, who also holds an appointment in MIT's Department of Brain and Cognitive Sciences. "Moreover, because there are many different types of neurons in the cerebral cortex, it is likely that we will have to figure out how to program stem cells to become many different types of neurons, each of them with a different set of pre-specified connections."
"In the stem cell field, it is generally thought that the main limitation to achieve brain repair is simply for the new neurons to reach a given brain region and to ensure their survival. Once there, it has been assumed that stem cells will 'know what to do' and will become the type of neuron that is missing. It seems that is not the case at all. Our experiments indicate that things are much more complicated," Lois said.
Lois and colleagues from MIT's departments of Brain and Cognitive Sciences and Biology found that the stem cells give rise to neurons that become a very specific neuronal type that is already pre-specified to make a very defined set of connections and not others.
Even if the stem cells are transplanted to other parts of the brain, they do not change the type of connections they are programmed to make.
"This suggests that we will have to know much more about the different types of neuronal stem cells, and to identify the characteristic features of their progeny," Lois said. "We may need to have access to many different types of 'tailored' stem cells that give rise to many different types of neurons with specific connections. In addition, we may need a combination of several of these tailored stem cells to eventually be able to replace the different types of neurons lost in a given brain region.
Massachusetts Institute of Technology
"It is wishful thinking to hope that adult stem cells will be able to modify themselves so that they can become other types of neurons lost to injury or disease," said Carlos E. Lois, assistant professor of neuroscience in MIT's Picower Institute for Leaning and Memory.
In developing embryos, stem cells give rise to all the different types of cells that make up the body--skin, muscle, nerve, brain, blood and more. Some of these stem cells persist in adults and give rise to new skin cells, stomach lining cells, etc. The idea behind stem-cell therapy is to use these cells to repair tissue or organs ravaged by disease.
To realize this potential, the stem cells have to be "instructed" to become liver cells, heart cells or neurons. The MIT study, which looked only at adult neural stem cells, suggests it will be necessary to learn how to program any kind of stem cell-embryonic, adult or those derived through other means-to produce specific types of functioning neurons. Without this special set of instructions, a young neuron will only connect with the partners for which it was pre-programmed.
The adult brain harbors its own population of stem cells that spawn new neurons for life. The MIT study shows that a neural stem cell is irreversibly committed to produce only one type of neuron with a pre-set pattern of connections. This means that a given neuronal stem cell can have only limited use in replacement therapy.
"A stem cell that produces neurons that could be useful to replace neurons in the cerebral cortex (the type of neurons lost in Alzheimer's disease) will be most likely useless to replace neurons lost in the spinal cord," said Lois, who also holds an appointment in MIT's Department of Brain and Cognitive Sciences. "Moreover, because there are many different types of neurons in the cerebral cortex, it is likely that we will have to figure out how to program stem cells to become many different types of neurons, each of them with a different set of pre-specified connections."
"In the stem cell field, it is generally thought that the main limitation to achieve brain repair is simply for the new neurons to reach a given brain region and to ensure their survival. Once there, it has been assumed that stem cells will 'know what to do' and will become the type of neuron that is missing. It seems that is not the case at all. Our experiments indicate that things are much more complicated," Lois said.
Lois and colleagues from MIT's departments of Brain and Cognitive Sciences and Biology found that the stem cells give rise to neurons that become a very specific neuronal type that is already pre-specified to make a very defined set of connections and not others.
Even if the stem cells are transplanted to other parts of the brain, they do not change the type of connections they are programmed to make.
"This suggests that we will have to know much more about the different types of neuronal stem cells, and to identify the characteristic features of their progeny," Lois said. "We may need to have access to many different types of 'tailored' stem cells that give rise to many different types of neurons with specific connections. In addition, we may need a combination of several of these tailored stem cells to eventually be able to replace the different types of neurons lost in a given brain region.
Massachusetts Institute of Technology
Stem Cells Current Events and Stem Cells News RSSNew discovery about the formation of new brain cells
The generation of new nerve cells in the brain is regulated by a peptide known as C3a, which directly affects the stem cells' maturation into nerve cells and is also important for the migration of new nerve cells through the brain tissue, reveals new research from the Sahlgrenska Academy published in the journal Stem Cells.
Umbilical cord blood stem cell transplant may help lung, heart disorders
Two separate studies published in the current issue of Cell Transplantation (18:8), - now freely available on-line have shown that transplanted human-derived umbilical cord blood (UCB) stem cells transplanted in an animal model had positive therapeutic effects on specific lung and heart disorders the animal models.
Gene mismatch influences success of bone marrow transplants
A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics.
New research shows versatility of amniotic fluid stem cells
For the first time, scientists have demonstrated that stem cells found in amniotic fluid meet an important test of potential to become specialized cell types, which suggests they may be useful for treating a wider array of diseases and conditions than scientists originally thought.
First reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
Bone Implant Offers Hope for Skull Deformities
A synthetic bone matrix offers hope for babies born with craniosynostosis, a condition that causes the plates in the skull to fuse too soon.
Your Own Stem Cells Can Treat Heart Disease
The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.
Is hepatic differentiation of embryonic stem cells induced by valproic acid and cytokines?
Embryonic stem (ES) cells, known for their capacity to proliferate indefinitely and differentiate into almost all types of cells including hepatocytes, have raised the hope of cellular replacement therapy for liver failure.
Paradoxical protein might prevent cancer
One difficulty with fighting cancer cells is that they are similar in many respects to the body's stem cells. By focusing on the differences, researchers at Karolinska Institutet have found a new way of tackling colon cancer. The study is presented in the prestigious journal Cell.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
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