BACKGROUND： Due to the lack of autograft transplant rejection, Schwann cells （SCs） can promote the proliferation of embryonic stem cells and the induction of dopaminergic neurons. Mesencephalic stem cells can be in...BACKGROUND： Due to the lack of autograft transplant rejection, Schwann cells （SCs） can promote the proliferation of embryonic stem cells and the induction of dopaminergic neurons. Mesencephalic stem cells can be induced to produce dopaminergic neurons. The therapeutic effects of co-grafts of SCs and neural stem cells （NSCs） deserves further study and verification in Parkinsonian animal models. OBJECTIVE： To investigate the effects of Schwann cells and mesencephalic NSC co-grafts in Parkinsonian animal models on animal behavior and histology. DESIGN： Randomized controlled experiment. SETTING： Hehai University; Institute of Neuroscience, Chinese Academy of Sciences. MATERIALS： The following animals were obtained from the Experimental Animal Center, Shanghai Institute for Biological Science, Chinese Academy of Sciences： 5 Sprague-Dawley rats, embryonic day （E） 13-16; 16 neonatal Sprague-Dawley rats, postnatal day 1-3; and 18 adult SD rats of both genders. Animal experimentation met animal ethical approval. METHODS： The experiment was performed at the Department of Anatomy, Histology and Embryology, Shanghai Medical Center, Hehai University from September 2005 to January 2007. The mesencephalic NSCs were obtained from the brains of SD rats at E 13-16, and SCs were harvested from the sciatic nerves of neonatal rats at day 1-3. Hemiparkinsonian rats （n =18） were selected for transplantation after estimating rotational behavior in response to apomorphine and were randomly assigned to three groups： control group, NSC group, and co-graft group. There were 6 rats in each group. Either phosphate buffered saline （PBS）, NSCs, or SCs plus NSCs were transplanted into the right neostriatum of Parkinsonian rats, respectively. MAIN OUTCOME MEASURES： （1） Rotational behavior was induced by apomorphine （0.05 mg/kg, i.p.） 2, 4, 6, 8, and 10 weeks after transplantation, and the number of rotations were counted. （2） Differentiation and survival of dopaminergic neurons in the right neostriatum were quantified by tyrosine hydroxylase immunohistochemistry 10 weeks after grafting. RESULTS： All 18 Parkinsonian rats were included in the final analysis,without any loss. （1）Rotation behavior and turning： Compared with the control group, the percent of apomorphine-induced rotations were significantly decreased （P 〈 0.01 ） in both the NSC group and co-graft group. （2）Differentiation and survival of dopaminergic neurons in each group： TH-immunoreactive neurons were detected in the striatum of both the NSC group and co-graft group 10 weeks after transplantation. The neuronal volume, size of the nucleus, and neuronal numbers were larger in the co-graft group compared to the NSC group （P 〈 0.05）. CONCLUSION： SC and NSC co-grafts not only improve Parkinsonian behavior in rats, but also improve the survival of NSCs.展开更多
Parkinson’s disease is a neurodegenerative condition characterized by motor impairments caused by the selective loss of dopaminergic neurons in the substantia nigra.Levodopa is an effective and well-tolerated dopamin...Parkinson’s disease is a neurodegenerative condition characterized by motor impairments caused by the selective loss of dopaminergic neurons in the substantia nigra.Levodopa is an effective and well-tolerated dopamine replacement agent.However,levodopa provides only symptomatic improvements,without affecting the underlying pathology,and is associated with side effects after long-term use.Cell-based replacement is a promising strategy that offers the possibility to replace lost neurons in Parkinson’s disease treatment.Clinical studies of transplantation of human fetal ventral mesencephalic tissue have provided evidence that the grafted dopaminergic neurons can reinnervate the striatum,release dopamine,integrate into the host neural circuits,and improve motor functions.One of the limiting factors for cell therapy in Parkinson’s disease is the low survival rate of grafted dopaminergic cells.Different factors could cause cell death of dopaminergic neurons after grafting such as mechanical trauma,growth factor deprivation,hypoxia,and neuroinflammation.Neurotrophic factors play an essential role in the survival of grafted cells.However,direct,timely,and controllable delivery of neurotrophic factors into the brain faces important limitations.Different types of cells secrete neurotrophic factors constitutively and co-transplantation of these cells with dopaminergic neurons represents a feasible strategy to increase neuronal survival.In this review,we provide a general overview of the pioneering studies on cell transplantation developed in patients and animal models of Parkinson’s disease,with a focus on neurotrophic factor-secreting cells,with a particular interest in mesenchymal stromal cells;that co-implanted with dopaminergic neurons would serve as a strategy to increase cell survival and improve graft outcomes.展开更多
Intracerebral co-grafting of Schwann's cells and human fetal adrenal medullary tissue was performed in 10 patients with Parkinson's disease. One to six months after grafting, symptoms were improved significant...Intracerebral co-grafting of Schwann's cells and human fetal adrenal medullary tissue was performed in 10 patients with Parkinson's disease. One to six months after grafting, symptoms were improved significantly for 1 to 3 grade. Among them, 2 patients resumed nearly normal daily activities. Long-term follow-up showed that the symptoms were not improved satisfactorily in some patients. It is considered that careful selection of patients, administration of amantadine, and co-grafting of Schwann's cells which prompts the survival of chromaffin cells are essential to better results.展开更多
Neural stem cells （NSCs） are effective in treating Parkinsonian animals. Although cell transplantation is considered a promising treatment for Parkinson disease （PD）, its clinical use has been limited to only a fe...Neural stem cells （NSCs） are effective in treating Parkinsonian animals. Although cell transplantation is considered a promising treatment for Parkinson disease （PD）, its clinical use has been limited to only a few patients. The major limiting factors of this therapy are difficulty in obtaining sufficient viable embryonic mesencephalic tissue and the controversial ethical and/or legal issues raised by the use of human fetal allografts. Some reports suggest that Schwann cells （SCs） can promote the proliferation of embryonic stem cells and the induction of dopaminergic neurons. Our research focused on potential curative effects of co-graft SCs with mesencephalic stem cells into Parkinsonian animals and elucidating the underlying mechanisms.展开更多
文摘BACKGROUND： Due to the lack of autograft transplant rejection, Schwann cells （SCs） can promote the proliferation of embryonic stem cells and the induction of dopaminergic neurons. Mesencephalic stem cells can be induced to produce dopaminergic neurons. The therapeutic effects of co-grafts of SCs and neural stem cells （NSCs） deserves further study and verification in Parkinsonian animal models. OBJECTIVE： To investigate the effects of Schwann cells and mesencephalic NSC co-grafts in Parkinsonian animal models on animal behavior and histology. DESIGN： Randomized controlled experiment. SETTING： Hehai University; Institute of Neuroscience, Chinese Academy of Sciences. MATERIALS： The following animals were obtained from the Experimental Animal Center, Shanghai Institute for Biological Science, Chinese Academy of Sciences： 5 Sprague-Dawley rats, embryonic day （E） 13-16; 16 neonatal Sprague-Dawley rats, postnatal day 1-3; and 18 adult SD rats of both genders. Animal experimentation met animal ethical approval. METHODS： The experiment was performed at the Department of Anatomy, Histology and Embryology, Shanghai Medical Center, Hehai University from September 2005 to January 2007. The mesencephalic NSCs were obtained from the brains of SD rats at E 13-16, and SCs were harvested from the sciatic nerves of neonatal rats at day 1-3. Hemiparkinsonian rats （n =18） were selected for transplantation after estimating rotational behavior in response to apomorphine and were randomly assigned to three groups： control group, NSC group, and co-graft group. There were 6 rats in each group. Either phosphate buffered saline （PBS）, NSCs, or SCs plus NSCs were transplanted into the right neostriatum of Parkinsonian rats, respectively. MAIN OUTCOME MEASURES： （1） Rotational behavior was induced by apomorphine （0.05 mg/kg, i.p.） 2, 4, 6, 8, and 10 weeks after transplantation, and the number of rotations were counted. （2） Differentiation and survival of dopaminergic neurons in the right neostriatum were quantified by tyrosine hydroxylase immunohistochemistry 10 weeks after grafting. RESULTS： All 18 Parkinsonian rats were included in the final analysis,without any loss. （1）Rotation behavior and turning： Compared with the control group, the percent of apomorphine-induced rotations were significantly decreased （P 〈 0.01 ） in both the NSC group and co-graft group. （2）Differentiation and survival of dopaminergic neurons in each group： TH-immunoreactive neurons were detected in the striatum of both the NSC group and co-graft group 10 weeks after transplantation. The neuronal volume, size of the nucleus, and neuronal numbers were larger in the co-graft group compared to the NSC group （P 〈 0.05）. CONCLUSION： SC and NSC co-grafts not only improve Parkinsonian behavior in rats, but also improve the survival of NSCs.
基金supported by grants from Consellería de Cultura,Educación e Ordenación Universitaria,Xunta de Galicia(ED431G/05,ED431C 2018/10)European Regional Development Fund(FEDER),Instituto de Salud CarlosⅢ(RD16/011/0016,RD21/0017/0031)Secretaría de Estado de Investigación,Desarrollo e Innovación(Grant/Award,number RTI2018-098830-B-I00)(to JLLG)。
文摘Parkinson’s disease is a neurodegenerative condition characterized by motor impairments caused by the selective loss of dopaminergic neurons in the substantia nigra.Levodopa is an effective and well-tolerated dopamine replacement agent.However,levodopa provides only symptomatic improvements,without affecting the underlying pathology,and is associated with side effects after long-term use.Cell-based replacement is a promising strategy that offers the possibility to replace lost neurons in Parkinson’s disease treatment.Clinical studies of transplantation of human fetal ventral mesencephalic tissue have provided evidence that the grafted dopaminergic neurons can reinnervate the striatum,release dopamine,integrate into the host neural circuits,and improve motor functions.One of the limiting factors for cell therapy in Parkinson’s disease is the low survival rate of grafted dopaminergic cells.Different factors could cause cell death of dopaminergic neurons after grafting such as mechanical trauma,growth factor deprivation,hypoxia,and neuroinflammation.Neurotrophic factors play an essential role in the survival of grafted cells.However,direct,timely,and controllable delivery of neurotrophic factors into the brain faces important limitations.Different types of cells secrete neurotrophic factors constitutively and co-transplantation of these cells with dopaminergic neurons represents a feasible strategy to increase neuronal survival.In this review,we provide a general overview of the pioneering studies on cell transplantation developed in patients and animal models of Parkinson’s disease,with a focus on neurotrophic factor-secreting cells,with a particular interest in mesenchymal stromal cells;that co-implanted with dopaminergic neurons would serve as a strategy to increase cell survival and improve graft outcomes.
文摘Intracerebral co-grafting of Schwann's cells and human fetal adrenal medullary tissue was performed in 10 patients with Parkinson's disease. One to six months after grafting, symptoms were improved significantly for 1 to 3 grade. Among them, 2 patients resumed nearly normal daily activities. Long-term follow-up showed that the symptoms were not improved satisfactorily in some patients. It is considered that careful selection of patients, administration of amantadine, and co-grafting of Schwann's cells which prompts the survival of chromaffin cells are essential to better results.
文摘Neural stem cells （NSCs） are effective in treating Parkinsonian animals. Although cell transplantation is considered a promising treatment for Parkinson disease （PD）, its clinical use has been limited to only a few patients. The major limiting factors of this therapy are difficulty in obtaining sufficient viable embryonic mesencephalic tissue and the controversial ethical and/or legal issues raised by the use of human fetal allografts. Some reports suggest that Schwann cells （SCs） can promote the proliferation of embryonic stem cells and the induction of dopaminergic neurons. Our research focused on potential curative effects of co-graft SCs with mesencephalic stem cells into Parkinsonian animals and elucidating the underlying mechanisms.
