Isolation and Cloning of Multipotential Stem Cells from the Embryonic Human CNS and Establishment of Transplantable Human Neural Stem Cell Lines by Epigenetic Stimulation

Vescovi, Angelo L.; Parati, Eugenio; Gritti, Angela; Poulin, Paule; Ferrario, Marina; Wanke, Enzo; Frölichsthal-Schoeller, Paola; Cova, Lidia; Arcellana‐Panlilio, Mayi; Colombo, Augusto; Galli, Rossella

doi:10.1006/exnr.1998.6998

Cited by 522 publications

(391 citation statements)

References 55 publications

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“…20 Thus, neuronal replacement in the spinal cord is feasible but requires grafting pre-differentiated stem cells or neuronal precursor cells. 21 It seems that cell transplantation at 7 days after SCI may have the best result.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of a combination of autologous neural differentiated and undifferentiated mesenchymal stem cells into injured spinal cord of rats

et al. 2009

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Study design: The use of stem cells for functional recovery after spinal cord injury. Objective: The aim of this study was to evaluate the effects of a combination of autologous undifferentiated and neural-induced bone marrow mesenchymal stem cells (MSCs) on behavioral improvement in rats after inducing spinal cord injury and comparing with transplantation of undifferentiated and neural-induced MSCs alone. Setting: The study was conducted at the department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. Methods: The spinal cord was injured by contusion using a Fogarty embolectomy catheter at the T8-T9 level of the spinal cord, and autologous MSCs were transplanted into the center of the developing lesion cavity, 3 mm cranial and 3 mm caudal to the cavity, at 7 days after induction of spinal cord compression injury. Results: At 5 weeks after transplantation, the presence of transplanted cells was detected in the spinal cord parenchyma using immunohistochemistry analysis. In all treatment groups (differentiated, undifferentiated and mix), there was less cavitation than lesion sites in the control group. The BassoBeattie-Bresnahan (BBB) score was significantly higher in rats transplanted with a combination of cells and in rats transplanted with neural-induced MSCs alone than in undifferentiated and control rats. Conclusion: Pre-differentiation of MSCs to neuron-like cells has a very important role in achieving the best results for functional improvement.

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Section: Discussionmentioning

confidence: 99%

Transplantation of a combination of autologous neural differentiated and undifferentiated mesenchymal stem cells into injured spinal cord of rats

et al. 2009

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“…20,21 Furthermore, a number of reports have shown that hNPC can differentiate into both astrocytes and neurons following transplantation into the nervous system. 18,20,[22][23][24][25] We have previously shown that non-modified hNPC can lead to functional restoration in a model of Huntington's disease, potentially through neuroprotective effects on dying striatal neurons. 21 However, naïve hNPC alone do not have any significant functional effects in models of PD.…”

Section: Introductionmentioning

confidence: 99%

Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates

et al. 2005

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Glial cell line-derived neurotrophic factor (GDNF) has been shown to increase the survival and functioning of dopamine neurons in a variety of animal models and some recent human trials. However, delivery of any protein to the brain remains a challenge due to the blood/brain barrier. Here we show that human neural progenitor cells (hNPC) can be genetically modified to release glycosylated GDNF in vitro under an inducible promoter system. hNPC-GDNF were transplanted into the striatum of rats 10 days following a partial lesion of the dopamine system. At 2 weeks following transplantation, the cells had migrated within the striatum and were releasing physiologically relevant levels of GDNF. This was sufficient to increase host dopamine neuron survival and fiber outgrowth. At 5 weeks following grafting there was a strong trend towards functional improvement in transplanted animals and at 8 weeks the cells had migrated to fill most of the striatum and continued to release GDNF with transport to the substantia nigra. These cells could also survive and release GDNF 3 months following transplantation into the aged monkey brain. No tumors were found in any animal. hNPC can be genetically modified, and thereby represent a safe and powerful option for delivering growth factors to specific targets within the central nervous system for diseases such as Parkinson's.

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“…Multipotent neural stem cells (NSCs) have been identified and isolated from mammalian central nervous system [4][5][6] including embryonic and adult human brain [7][8][9][10][11][12][13][14][15]. However, human NSC lines which could be useful in clinical setting are difficult to establish in vitro and, several different approaches have been developed to overcome this problem.…”

Section: Introductionmentioning

confidence: 99%

Generation of human cortical neurons from a new immortal fetal neural stem cell line

Cacci

Villa

Parmar

et al. 2007

Experimental Cell Research

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Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia. and neurons (mostly glutamatergic and GABAergic, as well as tyrosine hydroxylase-positive, presumably dopaminergic neurons). RT-PCR analysis showed that the hc-NSCs retained expression of Pax6, Emx2 and Neurogenin2, which are genes associated with regionalization and cell commitment in cortical precursors during brain development. Our data indicate that this hc-NSC line could be useful for exploring the potential of human NSCs to replace dead or damaged cortical cells in animal models of acute and chronic neurodegenerative diseases. Taking advantage of its clonality and homogeneity, this cell line will also be a valuable experimental tool to study the regulatory role of intrinsic and extrinsic factors in human NSC biology. (c) 2006 Elsevier Inc. All rights reserved

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Isolation and Cloning of Multipotential Stem Cells from the Embryonic Human CNS and Establishment of Transplantable Human Neural Stem Cell Lines by Epigenetic Stimulation

Cited by 522 publications

References 55 publications

Transplantation of a combination of autologous neural differentiated and undifferentiated mesenchymal stem cells into injured spinal cord of rats

Transplantation of a combination of autologous neural differentiated and undifferentiated mesenchymal stem cells into injured spinal cord of rats

Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates

Generation of human cortical neurons from a new immortal fetal neural stem cell line

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