\ ALS Research \ Stemcells: We Know They Can Divide
We Know They Can Divide, But Can They Conquer ALS?
By Laurie LaRusso, MS, ELS
Note: The ALS Society of Canada shares this article with permission from the ALS Therapy Development Foundation. In this rapidly growing field of investigation there are many unanswered questions. This article gives some context for ALS stem cell research expressed in easily understood terms. A number of researchers in Canada are exploring this field, but much work needs to be done before there are treatment options for those with ALS.
Stem cells sound like the answer to our prayers. For people with ALS and other neurodegenerative disorders, stem cells may some day provide replacement neurons for those ravaged by disease. But what exactly are stem cells? And what can we realistically expect from stem cell therapy?
Simple Cells, Plentiful Possibilities
Stem cells are cells from the earliest stages of human development. While still in the womb, these cells divide repeatedly and produce the cells of our growing tissues through self-renewal. Now scientists are learning how to grow stem cells in the laboratory that will divide indefinitely and differentiate into other types of cells in the body, such as blood cells and brain cells. The fact that these cells can literally become neurons is what makes them so promising as a therapy for neurodegenerative disorders. And the capacity to divide indefinitely suggests they might provide an endless supply of new cells for transplantation.
ALS symptoms are the result of motor neuron death. Will giving ALS patients new motor neurons solve the problem? Possibly. But there is more to curing neurodegenerative diseases than simply replacing damaged neurons. Before stem cells can be called upon to replace or restore damaged neurons in ALS patients, the ongoing damage to motor neurons must be stopped.
Neurons in Need: How Can Stem Cells Help?
Stem cells from several sources can develop into neurons. Researchers are studying these cells as potential therapies to replace damaged neurons in Parkinson’s disease, stroke, Alzheimer’s disease, ALS, and spinal cord injury. Recent testing in some animal models of these conditions have shown promise but the story in ALS is still ambiguous.
These conditions share one thing in common: neuron death. However, they also differ in very significant ways: 1. The nature of neuron injury (acute, one-time event in stroke versus recurrent injury in ALS), 2. Type and location of damaged neurons (motor neurons in the brain stem and spinal cord in ALS), 3. Cause of neuron death (lack of oxygen in stroke versus inflammation and amyloid plaques in Alzheimer’s).
To benefit ALS patients, stem cells would have to not only replace damaged neurons and spur functional recovery (neuroregeneration), but also protect neurons from injury (neuroprotection). Unfortunately, data from animal testing indicates that using stem cells to treat chronic diseases, such as ALS, is complex and presents significant hurdles.
The Hurdles
At this time, there is little evidence that transplanted neurons can transmit nerve impulses properly. In Parkinson’s disease research, scientists have had some success using stem cells to replace defunct dopamine-producing cells. However, in spinal cord injury and stroke, where nerve impulse transmission is required, transplanted cells have yet to show significant benefits. Technologies that could channel neurons in the right direction for proper nerve conduction may take 5 to 10 years to develop.
Recently, a controversial paper suggested that stem cells may not be differentiating after all. Based on two published papers, it appeared that stem cell fused with existing cells in the body, which made them appear as if they had differentiated. This news is troubling and needs to be thoroughly investigated because it represents a potential danger to patients.
HOW MIGHT STEM CELLS HELP ALS PATIENTS?
If scientists can discover a means to prevent further motor neuron death in ALS patients, stem cells may help restore motor neuron function. Current research on stem cells in mouse and rat models of ALS has yielded mixed results to date.
Researchers at Johns Hopkins tested stem cells in a viral injury model of motor neuron death that produces ALS-like symptoms. They injected stem cells derived from fetal tissue into the spinal fluid of rats infected with the Sindbis virus, which causes paralysis of the hind limbs. Fifty percent of the rodents treated with stem cells displayed functional improvements in movement of their hind legs. In addition, the stem cells they injected migrated to the damaged area and 5-7% of them appeared to differentiate into neuron-like cells.
Although these results are promising, they do not address the issue of arresting the disease and do not demonstrate that transplanted cells take on a functional or supportive role for existing neurons. In addition, this research employed an acute viral injury model of ALS rather than the SOD mouse model, which more closely reflects the chronic neuron injury characteristic of ALS.
Despite numerous attempts in SOD mice, embryonic stem cell transplants have failed to significantly extend life in SOD mice. However, pig neural cells and cord blood-derived stem cells each produced significant life extension in SOD mice. It’s not yet clear how these stem cells produced this benefit. It’s most likely that the cells prevented neuron death by providing growth factors and immune system modulation, rather than actively differentiating into neurons.
Another stem cells approach involves proteins called growth factors that may be able to activate proteins called growth factors may be able to activate the small number of adult stem cells already in the human brain to jump-start the brain’s own repair process. In rat models of Parkinson’s disease, injecting transforming growth factor (TGF) alpha has been shown to produce proliferation of stem cells, migration to the damaged areas, and differentiation into dopamine-producing neurons. However, clinical trials of brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) have been disappointing. Dosage and delivery method of growth factor therapies have yet to be determined and are difficult problems to solve.
What’s Available:
We now know that stem cells can be derived from human embryos, fetal tissue, and from adult tissue, including bone marrow, skin and blood. Studies, mainly in mice, have demonstrated that stem cells can be coaxed to differentiate into specific cell types and that such cells can be successfully transplanted. However, a considerable amount of time is needed to identify:
1) the right stem cells for treating ALS,
2) the correct site and method of transplantation,
3) chemicals to encourage growth and differentiation of stem cells, and
4) anti-rejection therapies as well as establishing the safety of transplantation.
Here’s a look at stem cells that may be available in the near and distant future:
Now: Currently, adult and cord blood-derived stem cells are used in humans to treat cancers, such as leukemia and lymphoma, and are being tested in clinical trials of multiple sclerosis and rheumatoid arthritis. Preclinical data on adult bone marrow stem cells in stroke and Parkinson’s disease make them attractive candidates for neuroregenerative therapies.
Soon: Neuronal stem cells derived from embryonic carcinoma cells are currently being tested in humans to repair stroke damage. In addition, stem cells derived from fetal tissue and from pigs have been tested in human models of Parkinson’s disease with promising results. Though promising, it’s estimated that such therapies will not be available for at least 2 to 5 years.
Long-term: In the best-case scenario, using fetal tissue stem cells lik
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Stemcells: We Know They Can Divide
Stem CellsWe Know They Can Divide, But Can They Conquer ALS?
By Laurie LaRusso, MS, ELS
Note: The ALS Society of Canada shares this article with permission from the ALS Therapy Development Foundation. In this rapidly growing field of investigation there are many unanswered questions. This article gives some context for ALS stem cell research expressed in easily understood terms. A number of researchers in Canada are exploring this field, but much work needs to be done before there are treatment options for those with ALS.
Stem cells sound like the answer to our prayers. For people with ALS and other neurodegenerative disorders, stem cells may some day provide replacement neurons for those ravaged by disease. But what exactly are stem cells? And what can we realistically expect from stem cell therapy?
Simple Cells, Plentiful Possibilities
Stem cells are cells from the earliest stages of human development. While still in the womb, these cells divide repeatedly and produce the cells of our growing tissues through self-renewal. Now scientists are learning how to grow stem cells in the laboratory that will divide indefinitely and differentiate into other types of cells in the body, such as blood cells and brain cells. The fact that these cells can literally become neurons is what makes them so promising as a therapy for neurodegenerative disorders. And the capacity to divide indefinitely suggests they might provide an endless supply of new cells for transplantation.
ALS symptoms are the result of motor neuron death. Will giving ALS patients new motor neurons solve the problem? Possibly. But there is more to curing neurodegenerative diseases than simply replacing damaged neurons. Before stem cells can be called upon to replace or restore damaged neurons in ALS patients, the ongoing damage to motor neurons must be stopped.
Neurons in Need: How Can Stem Cells Help?
Stem cells from several sources can develop into neurons. Researchers are studying these cells as potential therapies to replace damaged neurons in Parkinson’s disease, stroke, Alzheimer’s disease, ALS, and spinal cord injury. Recent testing in some animal models of these conditions have shown promise but the story in ALS is still ambiguous.
These conditions share one thing in common: neuron death. However, they also differ in very significant ways: 1. The nature of neuron injury (acute, one-time event in stroke versus recurrent injury in ALS), 2. Type and location of damaged neurons (motor neurons in the brain stem and spinal cord in ALS), 3. Cause of neuron death (lack of oxygen in stroke versus inflammation and amyloid plaques in Alzheimer’s).
To benefit ALS patients, stem cells would have to not only replace damaged neurons and spur functional recovery (neuroregeneration), but also protect neurons from injury (neuroprotection). Unfortunately, data from animal testing indicates that using stem cells to treat chronic diseases, such as ALS, is complex and presents significant hurdles.
The Hurdles
At this time, there is little evidence that transplanted neurons can transmit nerve impulses properly. In Parkinson’s disease research, scientists have had some success using stem cells to replace defunct dopamine-producing cells. However, in spinal cord injury and stroke, where nerve impulse transmission is required, transplanted cells have yet to show significant benefits. Technologies that could channel neurons in the right direction for proper nerve conduction may take 5 to 10 years to develop.
Recently, a controversial paper suggested that stem cells may not be differentiating after all. Based on two published papers, it appeared that stem cell fused with existing cells in the body, which made them appear as if they had differentiated. This news is troubling and needs to be thoroughly investigated because it represents a potential danger to patients.
HOW MIGHT STEM CELLS HELP ALS PATIENTS?
If scientists can discover a means to prevent further motor neuron death in ALS patients, stem cells may help restore motor neuron function. Current research on stem cells in mouse and rat models of ALS has yielded mixed results to date.
Researchers at Johns Hopkins tested stem cells in a viral injury model of motor neuron death that produces ALS-like symptoms. They injected stem cells derived from fetal tissue into the spinal fluid of rats infected with the Sindbis virus, which causes paralysis of the hind limbs. Fifty percent of the rodents treated with stem cells displayed functional improvements in movement of their hind legs. In addition, the stem cells they injected migrated to the damaged area and 5-7% of them appeared to differentiate into neuron-like cells.
Although these results are promising, they do not address the issue of arresting the disease and do not demonstrate that transplanted cells take on a functional or supportive role for existing neurons. In addition, this research employed an acute viral injury model of ALS rather than the SOD mouse model, which more closely reflects the chronic neuron injury characteristic of ALS.
Despite numerous attempts in SOD mice, embryonic stem cell transplants have failed to significantly extend life in SOD mice. However, pig neural cells and cord blood-derived stem cells each produced significant life extension in SOD mice. It’s not yet clear how these stem cells produced this benefit. It’s most likely that the cells prevented neuron death by providing growth factors and immune system modulation, rather than actively differentiating into neurons.
Another stem cells approach involves proteins called growth factors that may be able to activate proteins called growth factors may be able to activate the small number of adult stem cells already in the human brain to jump-start the brain’s own repair process. In rat models of Parkinson’s disease, injecting transforming growth factor (TGF) alpha has been shown to produce proliferation of stem cells, migration to the damaged areas, and differentiation into dopamine-producing neurons. However, clinical trials of brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) have been disappointing. Dosage and delivery method of growth factor therapies have yet to be determined and are difficult problems to solve.
What’s Available:
We now know that stem cells can be derived from human embryos, fetal tissue, and from adult tissue, including bone marrow, skin and blood. Studies, mainly in mice, have demonstrated that stem cells can be coaxed to differentiate into specific cell types and that such cells can be successfully transplanted. However, a considerable amount of time is needed to identify:
1) the right stem cells for treating ALS,
2) the correct site and method of transplantation,
3) chemicals to encourage growth and differentiation of stem cells, and
4) anti-rejection therapies as well as establishing the safety of transplantation.
Here’s a look at stem cells that may be available in the near and distant future:
Now: Currently, adult and cord blood-derived stem cells are used in humans to treat cancers, such as leukemia and lymphoma, and are being tested in clinical trials of multiple sclerosis and rheumatoid arthritis. Preclinical data on adult bone marrow stem cells in stroke and Parkinson’s disease make them attractive candidates for neuroregenerative therapies.
Soon: Neuronal stem cells derived from embryonic carcinoma cells are currently being tested in humans to repair stroke damage. In addition, stem cells derived from fetal tissue and from pigs have been tested in human models of Parkinson’s disease with promising results. Though promising, it’s estimated that such therapies will not be available for at least 2 to 5 years.
Long-term: In the best-case scenario, using fetal tissue stem cells lik
| Posted On: Wednesday, June 26, 2002 Modified: Thursday, June 27, 2002 Category: ALS Research Posted By: |