Stem cell therapy and the brain
The current interest in stem cell therapy for neurodegenerative diseases, such as in the study described in the previous article, has partially arisen due to the recognition that the dogma that the brain is a static organ with no possibility of cell regeneration in damaged areas is not true. It is now recognised that the adult brain can generate new neurons. Animal models and other studies have prompted hope that neural stem cell therapy will be a breakthrough in treatment of all kinds of neurodegenerative diseases. Results in some cases are promising, but it is important to recognise problems and limitations in the field as well.
In the case of Parkinson's disease, in which dopaminergic neuron cells are lost, promising results have been obtained in rat models of the disease. Rat neural stem cells were constructed to endogenously express the growth factor neurotrophin-3 (NT-3). These cells, termed rNSC-NT3, were transplanted into the Parkinson's disease model,
6-hydroxydopamine (6-OHDA)-treated Parkinsonian rats. Results indicated this reversed the main symptoms of the Parkinson's disease and apomorphine-induced rotational asymmetry and improved spatial learning ability. Furthermore, rNSC-NT3 were able to differentiate into dopaminergic neurons in different areas of the brain and exerted positive effects on neural stems cells via endogenously expressed NT-3. Thus, stem cells expressing NT-3 endogenously would appear to be a good candidate for stem cell therapy in Parkinson's disease. Parkinson's disease is considered to be one of the more promising neurodegenerative diseases for targeting with adult stem cell therapy.
Recent studies have considered the possibilitis for stem cell therapy in autism. A study to determine the safety and efficacy of combined transplantation of human cord blood mononuclear cells (CBMNCs) and umbilical cord-derived mesenchymal stem cells (UCMSCs) in children with autism was recently published in the Journal of Translational Medicine. No safety issues were observed. Treatment groups who received either CBMNC with rehabilitative therapy or both CBMNCs and UCMSCs with rehabilitative therapy showed signifincant therapeutic effects on measures including the Childhood Autism Rating Scale (CARS), Clinical Global Impression (CGI) scale and Aberrant Behavior Checklist (ABC) compared to the control, untreated group.
One drawback in adult stem cell therapy involves the relative scarcity of adult stem cells and also the difficulties inherent in harvesting them. One surprising suggestion for a potential source of neural stem cells are tooth tissues, which are accessible and provide a source of neural crest-derived ectomesenchymal stem cells (EMSCs). These have been successfully used in regenerative dentistry, however they have been suggested as potential sources for neural regeneration as they are highly proliferative and retain a neural-like phenotype in vitro. The local tissue and cell environment can also be a drawback in potential use of stem cell therapy in neurodegenerative diseases. For example, in the case of Amyotrophic lateral sclerosis (ALS), a motor neuron disease with devastating symptoms, in vitro co-culture systems suggest that reactive oxygen and nitrogen species released from the endogenous overactivated microglia directly destroy transplanted human neural stem cells.
Adult neural stem cell transplantaion is an area of promise in treatment of neurodegenerative diseases, but there are still problems to be overcome.
Sources
ENGLISH, D. et al., 2013. Neural stem cells-trends and advances. Journal of cellular biochemistry, 114(4), pp. 764-772
GU, S. et al., 2009. Combined treatment of neurotrophin-3 gene and neural stem cells is ameliorative to behavior recovery of Parkinson's disease rat model. Brain research, 1257, pp. 1-9
HESS, D.C. and BORLONGAN, C.V., 2008. Stem cells and neurological diseases. Cell proliferation, 41 Suppl 1, pp. 94-114
IBARRETXE, G. et al., 2012. Neural crest stem cells from dental tissues: a new hope for dental and neural regeneration. Stem Cells International, 2012, pp. 103503-103503
LETCHER, J.M. and COX, D.N., 2012. Adult neural stem cells: isolation and propagation. Methods in molecular biology (Clifton, N.J.), 823, pp. 279-293
LV, Y. et al., 2013. Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism. Journal Of Translational Medicine, 11(1), pp. 196-196
OWENS, C. and IRWIN, M., 2012. Neuroblastoma: the impact of biology and cooperation leading to personalized treatments. Critical reviews in clinical laboratory sciences, 49(3), pp. 85-115
THONHOFF, J.R. et al., 2011. Mutant SOD1 microglia-generated nitroxidative stress promotes toxicity to human fetal neural stem cell-derived motor neurons through direct damage and noxious interactions with astrocytes. American Journal Of Stem Cells, 1(1), pp. 2-21
The current interest in stem cell therapy for neurodegenerative diseases, such as in the study described in the previous article, has partially arisen due to the recognition that the dogma that the brain is a static organ with no possibility of cell regeneration in damaged areas is not true. It is now recognised that the adult brain can generate new neurons. Animal models and other studies have prompted hope that neural stem cell therapy will be a breakthrough in treatment of all kinds of neurodegenerative diseases. Results in some cases are promising, but it is important to recognise problems and limitations in the field as well.
In the case of Parkinson's disease, in which dopaminergic neuron cells are lost, promising results have been obtained in rat models of the disease. Rat neural stem cells were constructed to endogenously express the growth factor neurotrophin-3 (NT-3). These cells, termed rNSC-NT3, were transplanted into the Parkinson's disease model,
6-hydroxydopamine (6-OHDA)-treated Parkinsonian rats. Results indicated this reversed the main symptoms of the Parkinson's disease and apomorphine-induced rotational asymmetry and improved spatial learning ability. Furthermore, rNSC-NT3 were able to differentiate into dopaminergic neurons in different areas of the brain and exerted positive effects on neural stems cells via endogenously expressed NT-3. Thus, stem cells expressing NT-3 endogenously would appear to be a good candidate for stem cell therapy in Parkinson's disease. Parkinson's disease is considered to be one of the more promising neurodegenerative diseases for targeting with adult stem cell therapy.
Recent studies have considered the possibilitis for stem cell therapy in autism. A study to determine the safety and efficacy of combined transplantation of human cord blood mononuclear cells (CBMNCs) and umbilical cord-derived mesenchymal stem cells (UCMSCs) in children with autism was recently published in the Journal of Translational Medicine. No safety issues were observed. Treatment groups who received either CBMNC with rehabilitative therapy or both CBMNCs and UCMSCs with rehabilitative therapy showed signifincant therapeutic effects on measures including the Childhood Autism Rating Scale (CARS), Clinical Global Impression (CGI) scale and Aberrant Behavior Checklist (ABC) compared to the control, untreated group.
One drawback in adult stem cell therapy involves the relative scarcity of adult stem cells and also the difficulties inherent in harvesting them. One surprising suggestion for a potential source of neural stem cells are tooth tissues, which are accessible and provide a source of neural crest-derived ectomesenchymal stem cells (EMSCs). These have been successfully used in regenerative dentistry, however they have been suggested as potential sources for neural regeneration as they are highly proliferative and retain a neural-like phenotype in vitro. The local tissue and cell environment can also be a drawback in potential use of stem cell therapy in neurodegenerative diseases. For example, in the case of Amyotrophic lateral sclerosis (ALS), a motor neuron disease with devastating symptoms, in vitro co-culture systems suggest that reactive oxygen and nitrogen species released from the endogenous overactivated microglia directly destroy transplanted human neural stem cells.
Adult neural stem cell transplantaion is an area of promise in treatment of neurodegenerative diseases, but there are still problems to be overcome.
Sources
ENGLISH, D. et al., 2013. Neural stem cells-trends and advances. Journal of cellular biochemistry, 114(4), pp. 764-772
GU, S. et al., 2009. Combined treatment of neurotrophin-3 gene and neural stem cells is ameliorative to behavior recovery of Parkinson's disease rat model. Brain research, 1257, pp. 1-9
HESS, D.C. and BORLONGAN, C.V., 2008. Stem cells and neurological diseases. Cell proliferation, 41 Suppl 1, pp. 94-114
IBARRETXE, G. et al., 2012. Neural crest stem cells from dental tissues: a new hope for dental and neural regeneration. Stem Cells International, 2012, pp. 103503-103503
LETCHER, J.M. and COX, D.N., 2012. Adult neural stem cells: isolation and propagation. Methods in molecular biology (Clifton, N.J.), 823, pp. 279-293
LV, Y. et al., 2013. Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism. Journal Of Translational Medicine, 11(1), pp. 196-196
OWENS, C. and IRWIN, M., 2012. Neuroblastoma: the impact of biology and cooperation leading to personalized treatments. Critical reviews in clinical laboratory sciences, 49(3), pp. 85-115
THONHOFF, J.R. et al., 2011. Mutant SOD1 microglia-generated nitroxidative stress promotes toxicity to human fetal neural stem cell-derived motor neurons through direct damage and noxious interactions with astrocytes. American Journal Of Stem Cells, 1(1), pp. 2-21
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