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Background: Cerebral white matter injury (WMI) is the most common brain injury in preterm infants, leading to motor and developmental deficits often accompanied by cognitive impairment. However, there is no effective treatment. One promising approach for treating preterm WMI is cell replacement therapy, in which lost cells can be replaced by exogenous oligodendrocyte progenitor cells (OPCs). Methods: This study developed a method to differentiate human neural stem cells (hNSCs) into human OPCs (hOPCs). The preterm WMI animal model was established in rats on postnatal day 3, and OLIG2+/NG2+/PDGFRα+/O4+ hOPCs were enriched and transplanted into the corpus callosum on postnatal day 10. Then, histological analysis and electron microscopy were used to detect lesion structure; behavioral assays were performed to detect cognitive function. Results: Transplanted hOPCs survived and migrated throughout the major white matter tracts. Morphological differentiation of transplanted hOPCs was observed. Histological analysis revealed structural repair of lesioned areas. Re-myelination of the axons in the corpus callosum was confirmed by electron microscopy. The Morris water maze test revealed cognitive function recovery. Conclusion: Our study showed that exogenous hOPCs could differentiate into CC1+ OLS in the brain of WMI rats, improving their cognitive functions.
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Oligodendrocyte precursor cells (OPCs) can differentiate into myelinating oligodendrocytes during embryonic development, thereby representing an important potential source for myelin repair or regeneration. To the best of our knowledge, there are very few OPCs from human sources (human-derived OPCs [hOPCs]). In this study, we aimed to evaluate the safety and remyelination capacity of hOPCs developed in our laboratory, transplanted into the lateral ventricles of young animals. Several acute and chronic toxicity experiments were conducted in which different doses of hOPCs were transplanted into the lateral ventricles of Sprague-Dawley rats of different ages. The toxicity, biodistribution, and tumor formation ability of the injected hOPCs were examined by evaluating the rats' vital signs, developmental indicators, neural reflexes, as well as by hematology, immunology, and pathology. In addition, the hOPCs were transplanted into the corpus callosum of the shiverer mouse to verify cell myelination efficacy. Overall, our results show that transplanted hOPCs into young mice are nontoxic to their organ function or immune system. The transplanted cells engrafted in the brain and did not appear in other organs, nor did they cause tissue proliferation or tumor formation. In terms of efficacy, the transplanted hOPCs were able to form myelin in the corpus callosum, alleviate the trembling phenotype of shiverer mice, and promote normal development. The transplantation of hOPCs is safe; they can effectively form myelin in the brain, thereby providing a theoretical basis for the future clinical transplantation of hOPCs.
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Células Precursoras de Oligodendrócitos , Animais , Diferenciação Celular , Humanos , Camundongos , Bainha de Mielina/metabolismo , Oligodendroglia , Ratos , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
Objective To investigate the effects of the transplantation of autologous and allogeneic adipose-derived mesenchymal stem cells (ADMSCs) on the cardiac function in rats with acute myocardial infarction (AMI). Methods Firstly, ADMSCs were isolated from BN and Lewis rats, and the third generation were labeled with CM-DiI. Then 45 male Lewis rats were randomly divided into 3 groups (control group, autologous cell transplantation group, and allogeneic cell transplantation group). The AMI model was established by ligating the rats' left anterior descending artery, and then the infarcted myocardium as well as the peripheral parts was injected by the labeled ADMSCs via the endocardium. At 7 days after ADMSC transplantation, the infiltration of CD4+ T lymphocytes, CD8+ T lymphocytes and CD68+ macrophages were detected by immunofluorescence technique. At 7, 14 and 28 days after transplantation, survival rate of the transplanted cells was compared. Then echocardiography was used to detect the rats' cardiac function at 28 days after transplantation. And the expression of α-smooth muscle actin (α-SMA) was detected by immunofluorescence technique for determining the angiogenesis near the transplanted cells. Results The positive rate of the cells labeled with CM-DiI was nearly 100%. At 7 days after transplantation, lymphocyte infiltration and macrophages were observed around the transplanted cells in the allogeneic cell transplantation group. No lymphocyte infiltration and macrophages were observed in the autologous cell transplantation group. Compared with allogeneic cell transplantation, the survival rate of the transplanted cells increased significantly. Moreover, the left ventricular short axis shortening rate (LVFS) and the diastolic left ventricular anterior wall thickness (LVAWTd) increased at 7, 14 and 28 days after transplantation. Meanwhile, the number of angiogenesis around the infarcted myocardium also significantly increased. Conclusion Autologous ADMSC transplantation is significantly better at improving cardiac function in AMI rats than allogeneic ADMSC transplantation.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Infarto do Miocárdio , Animais , Masculino , Obesidade , Ratos , Ratos Endogâmicos LewRESUMO
OBJECTIVE: To investigate growth factor changes in cerebrospinal fluid (CSF) of children with mental retardation (MR) before and after neural precursor cell transplantation (NPCT), in an attempt to provide experimental support for the clinical treatment of MR with NPCT. METHODS: The study comprised of 28 MR children who received twice NPCT in our hospital. CSF was collected at both times of NPCT to assess growth factors by ELISA. In addition, the content of insulinlike growth factor 1 (IGF-1) in CSF was assayed to determine possible correlations between IGF-1 changes and the short-term therapeutic effect of NPCT. RESULTS: Of all the growth factors detected in CSF, only IGF-1 was increased significantly after NPCT (P<0.05). Fifteen of the twenty-eight MR children achieved short-term therapeutic efficacy, whereby the content of IGF-1 after NPCT was significantly higher than that before NPCT (P<0.05). There was no difference in IGF-1 content before and after NPCT in the remaining 13 MR children without shortterm therapeutic effect (P=0.657). There was a significant difference in IGF-change between the two groups of patients (P<0.05). CONCLUSION: IGF-1 may be one of the mechanisms contributing to the therapeutic effect of NPCT.
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Fator de Crescimento Insulin-Like I/líquido cefalorraquidiano , Deficiência Intelectual/líquido cefalorraquidiano , Células-Tronco Neurais/transplante , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Deficiência Intelectual/cirurgia , Peptídeos e Proteínas de Sinalização Intercelular/líquido cefalorraquidiano , Masculino , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: This study was intended to observe electroencephalographic (EEG) changes and convulsion attacks in children receiving neural precursor cell transplantation, and to explore the possibility of electrophysiological changes and risk of convulsion occurrence after cell transplantation. METHOD: 228 children were included in this study who received neural precursor cell transplantation in our hospital between March 2008 and July 2012. No history of convulsion attacks was elicited before cell transplantation. Data about EEG change and convulsion occurrence before and after cell transplantation were analyzed statistically. RESULTS: Of the 228 pediatric patients, EEG improvement, deterioration and no significant change were observed in 60, 45 and 122 patients, respectively. One month after transplantation, four (1.76%) patients experienced new convulsions. Of the 227 patients, 25 showed increased and/or abnormal discharges on EEG. Of these, 19 underwent EEG re-examination six months post-operation. Except the convulsive cases mentioned above, there were no new cases of convulsions in the remaining patients. Of the 27 patients including those with abnormal discharge, increased discharge and convulsion attacks, 17 achieved varying degrees of therapeutic efficacy. CONCLUSION: Intraventricular transplantation of neural precursor cells is associated with EEG changes in some children and clinical convulsion attacks in individual patients. However, these abnormal changes do not last long and usually return to normal levels within 1-6 months after surgery, along with disappearance of convulsions. Simultaneous occurrence of EEG changes and convulsions do not appear to affect therapeutic efficacy.
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Transplante de Células/efeitos adversos , Eletroencefalografia , Células-Tronco Neurais/fisiologia , Complicações Pós-Operatórias/etiologia , Convulsões/etiologia , Doenças do Sistema Nervoso Central/cirurgia , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Complicações Pós-Operatórias/fisiopatologia , Estudos Retrospectivos , Convulsões/cirurgiaRESUMO
BACKGROUND: Cell therapies have shown to be able to improve neurological functions to some extent for patients with refractory central nervous system (CNS) diseases or damages. Meanwhile, increasing attention has been drawn to the operation-related and (or) cell-related adverse events when performing cell therapy. Our study is to explore the safety issue from 720 cases of neural progenitor cell (NPC) transplantation based on clinic manifestations and examinations. METHOD: A retrospective analysis of all adverse events associated with 720 cases of NPC transplantation by administering the cells into the ventricles was done. RESULTS: One hundred and sixty-six cases had postoperative crying and irritability, 69 with vomiting and 84 with fever. None of them had CNS infection, but 4 cases presented intracranial hemorrhage. One month after cell therapy, 568 cases did EEG test, in which 153 patients showed improvement, 74 had abnormal changes in and 341 cases had no changes in; two patients developed new-onset convulsions and 3 had recurrent convulsions; 6 cases had intracranial hemorrhage, but no other CNS sequelae left from the primary diseases. 180 patients were able to follow-up for their clinical evaluation and head MRI or CT examination 2 years after transplantation. All patients didn't show signs of tumorigenesis and no serious and irreversible operation- or cell-related adverse events. IN CONCLUSION: there are mild adverse reactions and reversible adverse events following cell transplantation, our study indicated that NPC transplantation is a safe therapy in clinical treatment. Further clinical trials are necessary to establish the safety of this therapy.
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Doenças do Sistema Nervoso/terapia , Células-Tronco Neurais/transplante , Transplante de Células-Tronco/efeitos adversos , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Células Cultivadas , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Doenças do Sistema Nervoso/diagnóstico por imagem , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/fisiopatologia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Estudos RetrospectivosRESUMO
This study aimed to investigate the clinical effect of transplantation of CD133⺠peripheral blood stem cells or umbilical cord mesenchymal stem cells via the hepatic artery in children with type II hyperammonemia and its possible action mechanism. Umbilical cord mesenchymal stem cells were obtained by collecting cord blood (100-150 mL) from healthy fetuses and separating stem cell suspension (5 mL) from the cord blood by hydroxyethyl starch sedimentation. CD133⺠peripheral blood stem cells were obtained by mobilizing peripheral blood from the fathers of sick children using recombinant human granulocyte colony-stimulating factor for 5 days, collecting mononuclear cells (120 mL), and separating out CD133⺠cells by sorting. With catheterization and percutaneous puncture, the obtained stem cells were slowly injected into the liver of sick children via the hepatic artery. The changes in clinical symptoms and laboratory indices such as blood ammonia, liver function, and arginine and citrulline concentrations were observed. After stem cell transplantation via the hepatic artery, the 6 children showed significantly decreased blood ammonia levels, and their blood ammonia levels slowly increased 1 to 2 weeks later, but remained below 100 µmol/L, and changes in glutamic-pyruvic transaminase levels were similar to blood ammonia. Plasma citrulline and arginine concentrations increased significantly after transplantation and the increase in citrulline level exceeded the increase in arginine level. An 8 months follow-up visit for one typical patient showed that the weight and height increased after transplantation and sleep was improved without night crying. The child could actively gaze at interesting objects instead of responding indifferently and started to say simple words. With regard to fine motor skills, the child could pinch things with the thumb and middle finger instead of displaying a lack of hand-eye coordination and progress was also made in gross motor skills. Gesell test showed that the child made progress for an average of 3.82 months in all areas. It was concluded that after stem cell transplantation, children with type II hyperammonemia have decreased blood ammonia levels, stable and improved liver function and steadily increased plasma citrulline and arginine concentrations. They display a progressive trend in such aspects as movement, language and environmental adaptability. It is hypothesized that stem cell transplantation via the hepatic artery partially or totally activates, or provides supplementary ornithine carbamoyl transferase, so that plasma citrulline and arginine concentrations increase and urea cycle disorder can be corrected to some extent.
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Hiperamonemia/cirurgia , Transplante de Células-Tronco , Antígeno AC133 , Amônia/sangue , Antígenos CD/análise , Arginina/sangue , Citrulina/sangue , Feminino , Glicoproteínas/análise , Artéria Hepática , Humanos , Hiperamonemia/sangue , Lactente , Masculino , Peptídeos/análiseRESUMO
OBJECTIVE: To assess the efficiency and safety of human neural progenitor cells (hNPCs) transplantation in the treatment of pervasive developmental disorder (PDD) in children. METHODS: Twenty-two children with PDD were treated, including 13 children with Rett syndrome and 9 children with autism. They accepted hNPCs transplantation voluntarily. hNPCs derived from aborted fetal tissue were injected into the lateral ventricle of the patients under supersonic guidance. All patients were assessed according to the Autism Behavior Checklist before operation, at one and six months post operation, and one year later. RESULTS: No delayed complications resulting from this therapy were observed. The clinical symptoms of 17 patients, including 8 patients with autism and 9 patients with Rett syndrome, improved in varying degrees. The assessment results of the Autism Behavior Checklist for children with autism showed that compared with pre-operative function, social communication scores were significantly reduced at six months after transplantation, and total scores and social communication and language scores were also significantly reduced 1 year after transplantation (P<0.05). CONCLUSIONS: These results suggest that hNPCs transplantation is effective and safe for treatment of PPD in children. It deserves a further study.
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Transtornos Globais do Desenvolvimento Infantil/terapia , Células-Tronco Neurais/transplante , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Síndrome de Rett/terapiaRESUMO
The purpose of this study was to investigate the clinical efficacy of neural stem/progenitor cell (NS/PC) transplantation to treat severe cortical visual impairment (CVI), a sequela of neonatal brain injury. Fifty-two patients with cerebral injury and CVI were randomly divided into two groups: the treatment group (n = 25, with the median age of 18 months) and the control group (n = 27, with the median age of 19.5 months). The treatment group received intracerebroventricular transplantation of human NS/PCs and rehabilitation training. The control group received rehabilitation only. The visual function was assessed by Holt's method at various time points after transplantation. One in five patients with fundus abnormalities accompanied by blindness regained light perception. The visual functions of 75% of the patients with normal fundus were improved by one level or more in a 2-year follow-up. The median efficacy appeared 60 days posttransplantation. The total effective rate of cell transplantation on visual improvement was 64% (16 patients of 25), among which one blind patient regained light perception, five (31.2%) CVI patients improved by one level, and 10 (62.5%) improved by more than one level. Functional magnetic resonance imaging (fMRI) in a subpopulation of patients showed enhanced signals in the occipital lobe, visual pathway, and apical lobe after transplantation. In the control group, four patients with fundus abnormalities showed no improvement. Nine of 23 CVI patients with normal fundus improved visual function by more than one level. At the 2-year follow-up, no blind patients showed visual improvement. The total effective rate was 33.33% (9 of 27 patients). Among those showing visual improvement in the control group, six patients (66.67%) improved by one level, and three (33.33%) by more than one level. The median efficacy occurred in 365 days. Human NS/PC transplantation is effective to treat patients with severe CVI after neonatal brain injury. Compared with the traditional rehabilitation training, cell transplantation showed not only earlier visual improvement but also higher improvement rates and degrees. This article is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.
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Lesões Encefálicas/terapia , Células-Tronco Neurais/transplante , Transtornos da Visão/terapia , Lesões Encefálicas/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , MasculinoRESUMO
OBJECTIVE: To study the clinical efficacy of transplantation of human neural progenitor cells (hNPCs) in the treatment of severe cerebral palsy (CP) in children. METHODS: Forty-five children with CP were voluntarily accepted transplantation of hNPCs. The cells obtained from the forebrain of 10 to 12-week-fetus were cultured and amplified into hNPCs. Then the hNPCs were injected into the cerebral ventricle of the patients with the supersonic guidance. RESULTS: Dyssomnia, irritability and muscular tension were improved in one patient 3 days after transplantation. The clinical improvements were observed in the majority of the patients 1 month after transplantation. The therapeutic effects slowed down 3 to 6 months after transplantation. One year after transplantation the gross and fine motor skills and the congnition ability in the transplantation group were considerably surpassed to those in the control group. No delayed severe complications were observed after transplantation. No tumorigenesis was noted 5 years after transplantation. CONCLUSIONS: The transplantation of hNPCs as a novel therapy is effective and safe for severe CP. Many investigations are needed to evaluate the effect of the therapy.
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Paralisia Cerebral/terapia , Células-Tronco Neurais/transplante , Pré-Escolar , Feminino , Humanos , Lactente , MasculinoRESUMO
Cerebral palsy (CP) is a chronic nervous system disease that severely damages the physical and developmental health of children. Traditional treatment brings about only improvement of mild to moderate CP, but severe CP still lacks effective interventions. To explore safety and efficacy of using neural progenitor cells (NPCs) to treat CP in children, we performed NPC transplantation in 45 patients with severe CP by injecting NPCs derived from aborted fetal tissue into the lateral ventricle. Gross motor function measures (GMFM), the Peabody Developmental Motor Scale-Fine Motor (PDMS-FM) test, and a unified survey questionnaire designed specifically for children with CP were used to evaluate neurological function of the patients. Motor development was significantly accelerated within the first month after cell transplantation, but the rate of improvement gradually slowed to preoperative levels. However, after 1 year, the developmental level in each functional sphere (gross motor, fine motor, and cognition) of the treatment group was significantly higher compared to the control group. No delayed complications of this therapy were noted. These results suggest that NPC transplantation is a safe and effective therapeutic method for treating children with severe CP.
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Transplante de Tecido Encefálico/métodos , Paralisia Cerebral/cirurgia , Células-Tronco Neurais/transplante , Transplante de Células-Tronco/métodos , Paralisia Cerebral/fisiopatologia , Paralisia Cerebral/reabilitação , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Células-Tronco Neurais/citologiaRESUMO
A total of 24 children with cerebral palsy were enrolled in this study and underwent ultrasound guided transplantation of neural stem cells through the lateral ventricle. Neural stem cells (3.8 × 10(6)-7.3 × 10(7)) were injected into the lateral ventricles. Mild injury of lateral ventricular blood vessels occurred in only two cases (8.3%). Seven cases (29.2%) experienced a fever. Clinical manifestations were improved to varying degrees in eight cases (28.0%) within 3 months after transplantation. Patient condition did not worsen, and no patient experienced severe adverse reactions.
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OBJECTIVE: To analyze the therapeutic effect of human neural precursor cells transplantation in treatment of neonates with severe brain injury. METHOD: The transplantation was performed on 6 newborns, one of them was diagnosed as extremely severe carbon monoxide poisoning at 5(th) day after birth; one of them was diagnosed as severe hypoglycemia; the others had asphyxia at birth with Apgar scores from 1 to 3 and were diagnosed as severe neonatal asphyxia, severe hypoxic ischemic encephalopathy according to images, electroencephalogram, biochemical examination and clinical manifestation. With the approval of hospital ethics committee and informed consent of the family members, the newborns received human neural precursor cells transplantation at the 4(th) to 20(th) day after birth. With the agreement of a pregnant woman, forebrain cells were obtained from the forebrain of her 12-week old fetus after spontaneous abortion. The cells from the fetal brain were amplified into human neural precursor cells in vitro and were injected into the cerebral ventricle of the patients. RESULT: On the 2(nd) day after transplantation, sucking and swallowing reflexes gradually appeared in all the patients, muscular tension was also improved, and convulsion stopped. NBNA scoring in 3 of the patients reached normal level on the 28(th) day after birth. The 6 patients were followed up for 12 months. Four patients were normal in psychomotor development and scores of each scale reached normal level. Two patients have cerebral palsy. CONCLUSION: hNPCs transplantation is safe and effective in treatment of severe neonatal brain injury. More clinical trials and further observation are needed.
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Lesões Encefálicas/cirurgia , Células-Tronco Neurais/transplante , Feminino , Humanos , Hipóxia-Isquemia Encefálica/cirurgia , Recém-Nascido , Masculino , Células-Tronco Neurais/citologiaRESUMO
OBJECTIVE: To study the effect of hyperbaric oxygenation (HBO) on the differentiation of the implanted human neural stem cells (hNSCs) into neurons in neonatal rats following hypoxic-ischemic brain damage (HIBD). METHODS: HIBD model was prepared by ligation of the left common carotid artery, followed by 8% hypoxia exposure in 7-day-old Sprague-Dawley rat pups. Three days later, the rats received implantation of hNSCs into the left cerebral ventricles. Then the survived rats were randomly divided into two groups: transplantation alone and transplantation+HBO (n=8 each). HBO treatment was administered (1.8 ATA, 1 hr once daily for 10 days) in the transplantation+HBO group 1 hr after hNSCs transplantation. Brains were removed 10 days after transplantation. Frozen coronal sections were prepared for immunofluorescence analysis to detect the neural differentiation of the transplanted cells in the cerebral cortex and hippocampus. RESULTS: Differentiated neurons of implanted cells distributed mainly in the cortex and the hippocampus of the injured side. There was no difference in the number of neurons in the cortex between the two groups, while the number of neurons in the hippocampus significantly increased in the transplantation+HBO group compared with that in the transplantation alone group (231.4+15.1 vs 162.6+5.6; P<0.05). CONCLUSIONS: HBO treatment may promote the differentiation of implanted hNSCs into neurons in the hippocampus of neonatal rats following HIBD.
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Oxigenoterapia Hiperbárica , Hipóxia-Isquemia Encefálica/terapia , Neurônios/citologia , Transplante de Células-Tronco , Animais , Animais Recém-Nascidos , Diferenciação Celular , Feminino , Humanos , Masculino , Ratos , Ratos Sprague-DawleyAssuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Osteopetrose/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Teste de Histocompatibilidade , Humanos , Lactente , Masculino , Osteopetrose/etiologia , Transplante HomólogoRESUMO
OBJECTIVE: Neonatal hypoxic-ischemic encephalopathy (HIE) harms the lives and health of newborn infants and children severely. Given the absence of effective therapies for HIE, it is important to derive new strategies. Neural stem cells (NSCs) have great potential as a therapeutic tool for the repair of a number of central nervous system disorders that involve cell loss. This study was designed to transplant the neural stem cells derived from human fetal brain (hNSCs) into cerebral ventricle of neonatal rat following hypoxic-ischemic injury and to investigate their survival, migration and differentiation in rat brain. METHODS: Cells obtained from the forebrain of a 12-week old fetus were cultured in the presence of epidermal growth factor, basic fibroblast growth factor and leukemia inhibitory factor for 11 days. Animal models were built in 7-day-postnatal Wistar rats, 3-days after hypoxia-ischemia (HI), 5 microl suspension containing 5.0 x 10(5) hNSCs was injected into the left cerebral ventricle of each HIE rat by using stereotactic instrument. No immunosuppression therapy was given to the animals. At 1, 2, 4 weeks and 3 months after transplantation, the rats were sacrificed and brain tissues were harvested and were then examined by H-E staining and immunohistochemical analysis. RESULTS: Implanted cells expressing human nuclear protein (hNP) migrated form the subventricular zone (SVZ) along corpus callosum to the damaged areas, especially to the injured side of cortex and hippocampus. In different areas, the implanted hNSCs differentiated into different cell types which were similar to the host cells. The 85% implanted cells in cortex consisted of hNuc-NF or hNuc-Tublin double positive cells, while in the migratory way, 60% implanted cells differentiated into hNuc-GFAP double positive cells. Compared with the 1-week time point, an increased number of hNP-positive cells were observed at 2-weeks, but the number of these cells greatly decreased at 4-weeks and 3 months. CONCLUSION: The implanted hNSCs could extensively survive, migrate in the brain of neonatal rat with HIE and could differentiate into neurons and astrocytes in a regionally specific manner.
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Encéfalo/patologia , Diferenciação Celular , Movimento Celular , Células-Tronco Fetais/transplante , Hipóxia-Isquemia Encefálica/patologia , Hipóxia-Isquemia Encefálica/terapia , Neurônios , Transplante de Células-Tronco/métodos , Animais , Animais Recém-Nascidos , Artéria Carótida Primitiva/cirurgia , Modelos Animais de Doenças , Humanos , Hipóxia/complicações , Hipóxia/fisiopatologia , Hipóxia-Isquemia Encefálica/fisiopatologia , Imuno-Histoquímica , Injeções Intraventriculares/métodos , Ligadura/métodos , Proteínas Nucleares/metabolismo , Ratos , Ratos Sprague-Dawley , Análise de Sobrevida , Fatores de TempoRESUMO
OBJECTIVE: Severe newborn hypoxic-ischemic encephalopathy (HIE) has a very high rate of disability and no effective treatment is available. The present study aimed to preliminarily evaluate the effects of human neural stem cell transplantation in treatment of severe neonatal HIE. METHODS: The patient was a 75-day old male infant with sequelae of severe HIE who had highly delayed development of intelligence and movement and myotonia. MRI showed multiple cerebromalacia and encephalatrophy. Cells obtained from the forebrain of an 11-week old fetus were cultured and amplified for 15 days. And then the human fetal neural stem cells were injected into cerebral ventricle of this infant. RESULTS: Twenty eight days after transplantation, remarkable improvement occurred not only in his myotonia but also in his intelligence and movement, which became similar to those of the normal infants of the same age. Positron emission tomography (PET) showed significantly increased radioactivity at temporal and occipital lobes which suggested that the cellular metabolism had increased greatly. CONCLUSION: The short-term effect of NSCs transplantation on the infant with severe HIE sequelae was significant. PET suggested that the implanted NSCs survived. Many more studies are needed to evaluate long-term effects of NSC transplantation in treatment of HIE.