The Science Behind It All
What are Stem Cells?
Types of Stem Cells
Where Stem Cells Can Be Found
Aims of Scientists
Producing Stem Cells
Potential of Stem Cells in Medicine
Stem cells offer the prospect of developing cell-based treatments, both to repair or replace tissues, for example in the case of fractures, burns and other injuries, and to treat degenerative diseases such as Alzheimer’s, cardiac failure, diabetes and Parkinson’s. These treatments are attractive due to their potential as a life-long cure, instead of being temporary. It has been proposed that stem cell research has the potential to cure many diseases and disorders, including those as follows.
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Repairing Internal Damage
Stem cells can be used in internal repair, as they can be implanted into the body where they migrate to the site of a wound by the action of enzyme HMGB1. This acts as a cytokine (type of chemical messenger) and stimulates migration and proliferation of mesangioblasts (vessel-associated stem cells.) When these stem cells are injected into a damaged artery, they migrate to muscles with high levels of HMGB1, suggesting that this protein could be inserted into the site of an injury to encourage stem cells to migrate and repair tissue. The binding of HMGB1 to the receptor for advanced glycation end products (RAGE) acts as a cytokine: it is secreted by macrophages and monocytes (types of white blood cells) and when activated by IL-1β and TNF of lipopolysaccharide it acts as a chemotattractant for myeloid and smooth muscle cells, enhances the expression of vascular adhesion molecules in endothelial cells and impairs the barrier function of intestinal epithelia. This all helps to repair the damaged tissue. Research has shown that α-sarcoglycan null dystrophic muscle contains high levels of HMGB1, however stem cells migrate to this muscle even if their receptor (RAGE) is disabled. This implies that interaction with HMGB1 and its receptor is not the only cause of migration and proliferation of stem cells- another pathway must also be present. These processes have been shown to work both in vivo and ex vitro, and bacterially made HMGB1 may be used experimentally or therapeutically to direct mesangioblast migration into nondystrophic muscle, or to enhance it in dystrophic muscle. Read the BBC news coverage on this story
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Repairing Internal Damage
Stem cells can be used in internal repair, as they can be implanted into the body where they migrate to the site of a wound by the action of enzyme HMGB1. This acts as a cytokine (type of chemical messenger) and stimulates migration and proliferation of mesangioblasts (vessel-associated stem cells.) When these stem cells are injected into a damaged artery, they migrate to muscles with high levels of HMGB1, suggesting that this protein could be inserted into the site of an injury to encourage stem cells to migrate and repair tissue. The binding of HMGB1 to the receptor for advanced glycation end products (RAGE) acts as a cytokine: it is secreted by macrophages and monocytes (types of white blood cells) and when activated by IL-1β and TNF of lipopolysaccharide it acts as a chemotattractant for myeloid and smooth muscle cells, enhances the expression of vascular adhesion molecules in endothelial cells and impairs the barrier function of intestinal epithelia. This all helps to repair the damaged tissue. Research has shown that α-sarcoglycan null dystrophic muscle contains high levels of HMGB1, however stem cells migrate to this muscle even if their receptor (RAGE) is disabled. This implies that interaction with HMGB1 and its receptor is not the only cause of migration and proliferation of stem cells- another pathway must also be present. These processes have been shown to work both in vivo and ex vitro, and bacterially made HMGB1 may be used experimentally or therapeutically to direct mesangioblast migration into nondystrophic muscle, or to enhance it in dystrophic muscle. Read the BBC news coverage on this story
To Test New Drugs
New medication could be tested on tissues created from human pluripotent stem cell lines, minimising the risk of human trials by extending understanding of the side effects of the drug. This would also allow testing on a wider range of cell types, giving a more accurate representation of how the human body would respond to the drug, and therefore a higher level of safety. |
Tissue or Organ Growth for Transplantation
Currently the demand for tissues and organs outweighs the supply from donors. Stem cells would provide a renewable source of replacement cells and tissues to treat diseases including Alzheimer’s, spinal cord injury, stroke, burns, heart disease, diabetes, cardiovascular disease, osteoarthritis, and rheumatoid arthritis, which all require replacement or regeneration of organs or tissues. It may become possible for laboratory grown tissues to be implanted into the body, produced by culture in the laboratory.
Currently the demand for tissues and organs outweighs the supply from donors. Stem cells would provide a renewable source of replacement cells and tissues to treat diseases including Alzheimer’s, spinal cord injury, stroke, burns, heart disease, diabetes, cardiovascular disease, osteoarthritis, and rheumatoid arthritis, which all require replacement or regeneration of organs or tissues. It may become possible for laboratory grown tissues to be implanted into the body, produced by culture in the laboratory.
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Position of basal forebrain cholinergic
neurons
Growth of Particular Cells
Neurological Disorders
Many neurological disorders such as Parkinson’s disease, stroke, multiple sclerosis and Alzheimer’s are caused by a loss of neurons and glial cells. Stem cells have been used to form these cells in culture as well as to stimulate the formation and prevent the death of neurons and glial cells, potentially slowing the onset of disorders and significantly reducing damage. Parkinson’s disease is a gradual loss of nigrostriatal dopamine containing neurons, and degeneration in non-dopaminergic neurons, resulting in the lack of the chemical dopamine causing impended muscle function.) Neural stem cells have the ability to differentiate into these cells and the three major cell types of the CNS: neurons, astrocytes and oligodendrocytes. Human lines of these cells can be generated in vitro from the human fetal telencephalon using a retroviral vector encoding v-myc. One particular line, HB1.F3 has the ability to differentiate into neuronal and glial cell lines, helping to repair damage in stroke, Parkinsons’ disease, Alzheimer’s and hyperactivity disorder. Basal forebrain cholinergic neurons, which have a role in memory function, can be formed from stem cell lines, and used to replace damaged cells in the brain of Alzheimer’s sufferers. These stem cells can be genetically engineered to produce similar cells which can further assist in treatment of neurological disorders. When implanted into the body, NSC cells were found to migrate to ischemic lesion sites and differentiate into neurons and glial cells, helping to repair damage. This creation of cells from stem cell lines provides a near limitless supply of neurons for research, enabling research into the cause of degeneration of cells in the brain and trialling of treatments.These methods are also being used to treat stroke patients, and a trial to this effect began in November 2010, where stem cells were inserted into the brain of a stroke patient. There is hope that the stem cells will be attracted by chemical signalling initiated by damage in the brain, helping to repair and replace damaged tissue.
Type One Diabetes
Secretion of insulin by β cells in islets of langerhans in the pancreas controls blood sugar levels. Type 1 diabetes generally results from autoimmune destruction of pancreatic islet β-cells, resulting in insulin deficiency and dependence on insulin treatment. Research suggests that pancreatic and hepatic cell types (hepatocytes, islet, acinar and ductal cells) have wide plasticity and can differentiate into each other under appropriate conditions. Cell trapping, a method similar to IPSC, involves the transfection of particular genes of these insulin-secreting cells into stem cells, controlled by the expression of neomycin. This results in IB/3x-99 clones, which can regulate hormone secretion in the presence of secretagogues. These cells can be inserted into the body, restoring near-physiological insulin secretion capacity, a method which has been successfully carried out on cadaveric allogenic islets. Further research attempts to understand the molecular mechanisms involved in differentiation, potentially allowing the stimulation of islet regeneration in situ. These methods could both correct hyperglycaemia or hypoglycaemia, simulating the normal function of the body. This offers an alternative to gene therapy and could mean that diabetes sufferers no longer have to rely on regular injections of insulin. Work so far has not yet produced cells with true beta cell phenotypes, although research is in progression.
Treatments For the Blind and Partially Sighted
Stem cells have been used in vitro to generate the retina of the eye, offering hope to the blind and partially sighted. Retinitis pigmentosa and age-related macular degeneration (AMD) are the most common causes of blindness in old age, and involve the gradual and normally irreversible destruction of retinal cells, resulting in death of photoreceptors, eventually causing blindness. Stem cells can be stimulated in vitro to develop the cells of the retinal pigment epithelium, which can be injected into the eye, restoring visual function and slowing degeneration. Stem cells can also be used to form the optic cup of an embryonic eye, which develops into the retina, suggesting that it may be possibly to make a whole eye. Read the BBC news coverage on this story.
Neurological Disorders
Many neurological disorders such as Parkinson’s disease, stroke, multiple sclerosis and Alzheimer’s are caused by a loss of neurons and glial cells. Stem cells have been used to form these cells in culture as well as to stimulate the formation and prevent the death of neurons and glial cells, potentially slowing the onset of disorders and significantly reducing damage. Parkinson’s disease is a gradual loss of nigrostriatal dopamine containing neurons, and degeneration in non-dopaminergic neurons, resulting in the lack of the chemical dopamine causing impended muscle function.) Neural stem cells have the ability to differentiate into these cells and the three major cell types of the CNS: neurons, astrocytes and oligodendrocytes. Human lines of these cells can be generated in vitro from the human fetal telencephalon using a retroviral vector encoding v-myc. One particular line, HB1.F3 has the ability to differentiate into neuronal and glial cell lines, helping to repair damage in stroke, Parkinsons’ disease, Alzheimer’s and hyperactivity disorder. Basal forebrain cholinergic neurons, which have a role in memory function, can be formed from stem cell lines, and used to replace damaged cells in the brain of Alzheimer’s sufferers. These stem cells can be genetically engineered to produce similar cells which can further assist in treatment of neurological disorders. When implanted into the body, NSC cells were found to migrate to ischemic lesion sites and differentiate into neurons and glial cells, helping to repair damage. This creation of cells from stem cell lines provides a near limitless supply of neurons for research, enabling research into the cause of degeneration of cells in the brain and trialling of treatments.These methods are also being used to treat stroke patients, and a trial to this effect began in November 2010, where stem cells were inserted into the brain of a stroke patient. There is hope that the stem cells will be attracted by chemical signalling initiated by damage in the brain, helping to repair and replace damaged tissue.
Type One Diabetes
Secretion of insulin by β cells in islets of langerhans in the pancreas controls blood sugar levels. Type 1 diabetes generally results from autoimmune destruction of pancreatic islet β-cells, resulting in insulin deficiency and dependence on insulin treatment. Research suggests that pancreatic and hepatic cell types (hepatocytes, islet, acinar and ductal cells) have wide plasticity and can differentiate into each other under appropriate conditions. Cell trapping, a method similar to IPSC, involves the transfection of particular genes of these insulin-secreting cells into stem cells, controlled by the expression of neomycin. This results in IB/3x-99 clones, which can regulate hormone secretion in the presence of secretagogues. These cells can be inserted into the body, restoring near-physiological insulin secretion capacity, a method which has been successfully carried out on cadaveric allogenic islets. Further research attempts to understand the molecular mechanisms involved in differentiation, potentially allowing the stimulation of islet regeneration in situ. These methods could both correct hyperglycaemia or hypoglycaemia, simulating the normal function of the body. This offers an alternative to gene therapy and could mean that diabetes sufferers no longer have to rely on regular injections of insulin. Work so far has not yet produced cells with true beta cell phenotypes, although research is in progression.
Treatments For the Blind and Partially Sighted
Stem cells have been used in vitro to generate the retina of the eye, offering hope to the blind and partially sighted. Retinitis pigmentosa and age-related macular degeneration (AMD) are the most common causes of blindness in old age, and involve the gradual and normally irreversible destruction of retinal cells, resulting in death of photoreceptors, eventually causing blindness. Stem cells can be stimulated in vitro to develop the cells of the retinal pigment epithelium, which can be injected into the eye, restoring visual function and slowing degeneration. Stem cells can also be used to form the optic cup of an embryonic eye, which develops into the retina, suggesting that it may be possibly to make a whole eye. Read the BBC news coverage on this story.
Heart Tissue
Research has shown that stem cells can be used to mend hearts in the laboratory, by stripping hearts of cells and using stem cells to repair the damage. Heart tissue can be grown in vitro and implanted into the body, overcoming problems of immune rejection (as cells could be made genetically identical to the recipient) and providing a limitless supply of heart tissue. Organisms such as zebra fish undergo a heart regeneration process naturally, and by understanding how this works, we could learn how to re-awaken the same developmental processes in humans, stimulating the body to heal itself.
Research has shown that stem cells can be used to mend hearts in the laboratory, by stripping hearts of cells and using stem cells to repair the damage. Heart tissue can be grown in vitro and implanted into the body, overcoming problems of immune rejection (as cells could be made genetically identical to the recipient) and providing a limitless supply of heart tissue. Organisms such as zebra fish undergo a heart regeneration process naturally, and by understanding how this works, we could learn how to re-awaken the same developmental processes in humans, stimulating the body to heal itself.
Studies into stem cell research will expand our knowledge of genetic and molecular controls of processes such as differentiation, which link to other conditions not directly involving stem cells, for which there may be found new strategies for therapy or cure. For example, cancer and birth defects arise from abnormal cell division and differentiation, and so from knowledge of stem cells, it may be possible to provide more effective treatments.