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Neural Stem Cell Transplantation (neural + stem_cell_transplantation)
Selected AbstractsMesencephalic human neural progenitor cells transplanted into the neonatal hemiparkinsonian rat striatum differentiate into neurons and improve motor behaviourJOURNAL OF ANATOMY, Issue 6 2006Marine Hovakimyan Abstract Neural stem cell transplantation is a promising strategy for the treatment of neurodegenerative diseases. To evaluate the differentiation potential of human neural progenitor cells (hNPCs) as a prerequisite for clinical trials, we intracerebrally transplanted in vitro expanded fetal mesencephalic hNPCs into hemiparkinsonian rats. On postnatal day one (P1), 17 animals underwent a unilateral intraventricular 6-hydroxydopamine injection into the right lateral ventricle. At P3, animals (n = 10) received about 100 000 hNPCs (1 µL) in the right striatum. Five weeks after birth, animals underwent behaviour tests prior to fixation, followed by immunohistochemistry on brain slices for human nuclei, glial fibrillary acidic protein, S100,, neuronal nuclei antigen, neuron-specific enolase and tyrosine hydroxylase. Compared with the apomorphine-induced rotations in the lesioned-only group (7.4 ± 0.5 min,1), lesioned and successfully transplanted animals (0.3 ± 0.1 min,1) showed a significant therapeutic improvement. Additionally, in the cylinder test, the lesioned-only animals preferred to use the ipsilateral forepaw. Conversely, the lesioned and transplanted animals showed no significant side bias similar to untreated control animals. Transplanted human nuclei-immunoreactive cells were found to survive and migrate up to 2000 µm into the host parenchyma, many containing the pan-neuronal markers neuronal nuclei antigen and neuron-specific enolase. In the striatum, tyrosine hydroxylase-immunoreactive somata were also found, indicating a dopaminergic differentiation capacity of transplanted hNPCs in vivo. However, the relative number of tyrosine hydroxylase-immunoreactive neurons in vivo seemed to be lower than in corresponding in vitro differentiation. To minimize donor tissue necessary for transplantation, further investigations will aim to enhance dopaminergic differentiation of transplanted cells in vivo. [source] Survival of neural precursor cells in growth factor-poor environment: Implications for transplantation in chronic diseaseGLIA, Issue 4 2006Ofira Einstein Abstract A key issue for therapeutic neural stem cell transplantation in chronic diseases is the long-term survival of transplanted cells in the brain. The normal adult central nervous system does not support the survival of transplanted cells. Presumably, the limited availability of trophic factors maintains the survival of resident cells but is insufficient for supporting the survival of transplanted cells. Specifically, in multiple sclerosis, a chronic relapsing disease, it would be necessary to maintain long-term survival of transplanted cells through phases of relapses and remissions. It may be beneficial to transplant cells as early as possible, in a form that will keep their survival independent of tissue support and ready for immediate mobilization upon tissue demand during disease relapse. In the present study, we examined whether, in the form of neurospheres, multipotential neural precursor cells (NPCs) survive in a growth factor-poor environment while maintaining their potential to respond to environmental cues. We found that after removal of growth factors from the culture medium of neurospheres in vitro, NPC proliferation decreased significantly, but most cells survived for a prolonged time and maintained their stem cell characteristics. After re-exposure to growth factors, neurosphere cells resumed proliferation and could differentiate along neural lineages. Furthermore, neurospheres, but not single NPCs, that were transplanted into the brain ventricles of intact animals survived within the ventricles for at least a month and responded to induction of experimental autoimmune encephalomyelitis and brain inflammation by extensive migration into the brain white matter and differentiated into glial lineage cells. © 2005 Wiley-Liss, Inc. [source] Human neural stem cell transplantation attenuates apoptosis and improves neurological functions after cerebral ischemia in ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2009P. ZHANG Background: Neuroprotection is a major therapeutic approach for ischemic brain injury. We investigated the neuroprotective effects induced by transplantation of human embryonic neural stem cells (NSCs) into the cortical penumbra 24 h after focal cerebral ischemia. Methods: NSCs were prepared from human embryonic brains obtained at 8 weeks of gestation. Focal cerebral ischemia was induced in adult rats by permanent occlusion of the middle cerebral artery. Animals were randomly divided into two groups: NSCs-grafted group and medium-grafted group (control). Infarct size was assessed 28 days after transplantation by hematoxylin and eosin staining. Neurological severity scores were evaluated before ischemia and at 1, 7, 14, and 28 days after transplantation. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and immunohistochemical analysis of Bcl-2 and Bax were performed at 7, 14, and 28 days after transplantation. Results: Physiological parameters of the two groups were comparable, but not significantly different. NSC transplantation significantly improved neurological function (P<0.05) but did not reduce the infarct size significantly (P>0.05). Compared with the control, NSC transplantation significantly reduced the number of TUNEL- and Bax-positive cells in the penumbra at 7 days. Interestingly, the number of Bcl-2-positive cells in the penumbra after NSC transplantation was significantly higher than that after medium transplantation (P<0.05). Conclusions: The results indicate that NSC transplantation has anti-apoptotic activity and can improve the neurological function; these effects are mediated by the up-regulation of Bcl-2 expression in the penumbra. [source] Intracerebral transplantation of neural stem cells combined with trehalose ingestion alleviates pathology in a mouse model of Huntington's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2009Chia-Ron Yang Abstract The present investigation examined the neuroprotective benefits for combined trehalose administration with C17.2 neural stem cell transplantation in a transgenic mouse model of Huntington's disease (HD), R6/2. C17.2 neural stem cells have the potential of differentiating into a neuronal phenotype in vitro and have been shown to be effective in the treatment of a variety of lysosomal lipid storage disorders in the nervous system. In this study, we transplanted these cells into the lateral ventricle of R6/2 transgenic mice in order to examine the efficacy of using these cells for correcting the accumulated polyglutamine storage materials in HD. To improve efficacy, animals were fed with a diet rich in trehalose, which has been shown to be beneficial to retard aggregate formation. The combined treatment strategy not only decreased ubiquitin-positive aggregation in striatum, alleviated polyglutamine aggregation formation, and reduced striatal volume, but also extended life span in the R6/2 animal model. Behavioral evaluation showed that the combination treatment improved motor function. Statistical analysis revealed that the combination treatment was more effective than treatment with trehalose alone on the basis of the above biochemical and behavioral criteria. This study provides a strong a basis for further developing an effective therapeutic strategy for HD. © 2008 Wiley-Liss, Inc. [source] | ||||||||||