scholarly journals Robust In Vivo Transduction of Nervous System and Neural Stem Cells by Early Gestational Intra Amniotic Gene Transfer Using Lentiviral Vector

2010 ◽  
Vol 18 (9) ◽  
pp. 1615-1623 ◽  
Author(s):  
David H Stitelman ◽  
Masayuki Endo ◽  
Archana Bora ◽  
Nidal Muvarak ◽  
Philip W Zoltick ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Gene Transfer ◽  
Neural Stem Cells ◽  
Lentiviral Vector

Successful treatment of murine β-thalassemia using in vivo selection of genetically modified, drug-resistant hematopoietic stem cells

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 506-513 ◽  
Author(s):  
Derek A. Persons ◽  
Esther R. Allay ◽  
Nobukuni Sawai ◽  
Phillip W. Hargrove ◽  
Thomas P. Brent ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Transfer ◽  
Hematopoietic Stem Cells ◽  
Bone Marrow Cells ◽  
Lentiviral Vector ◽  
Drug Resistant ◽  
Hematopoietic Stem ◽  
In Vivo Selection ◽  
Selection Of

AbstractSuccessful gene therapy of β-thalassemia will require replacement of the abnormal erythroid compartment with erythropoiesis derived from genetically corrected, autologous hematopoietic stem cells (HSCs). However, currently attainable gene transfer efficiencies into human HSCs are unlikely to yield sufficient numbers of corrected cells for a clinical benefit. Here, using a murine model of β-thalassemia, we demonstrate for the first time that selective enrichment in vivo of transplanted, drug-resistant HSCs can be used therapeutically and may therefore be a useful approach to overcome limiting gene transfer. We used an oncoretroviral vector to transfer a methylguanine methyltransferase (MGMT) drug-resistance gene into normal bone marrow cells. These cells were transplanted into β-thalassemic mice given nonmyeloablative pretransplantation conditioning with temozolomide (TMZ) and O6-benzylguanine (BG). A majority of mice receiving 2 additional courses of TMZ/BG demonstrated in vivo selection of the drug-resistant cells and amelioration of anemia, compared with untreated control animals. These results were extended using a novel γ-globin/MGMT dual gene lentiviral vector. Following drug treatment, normal mice that received transduced cells had an average 67-fold increase in γ-globin expressing red cells. These studies demonstrate that MGMT-based in vivo selection may be useful to increase genetically corrected cells to therapeutic levels in patients with β-thalassemia.

scholarly journals Expression and function of Ndel1 during the differentiation of neural stem cells induced by hippocampal exosomes

2020 ◽  
Author(s):  
WEN LI ◽  
Shanshan Wang ◽  
Hui He ◽  
Jianbing Qin ◽  
Xiang Cheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Western Blot ◽  
Hippocampal Neurogenesis ◽  
Quiescent State ◽  
Nervous System Diseases ◽  
And Function

Abstract BackgroundIn the brain of adult mammals, neural stem cells persist in the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus, which are specialized niches with proliferative capacity. Most neural stem cells are in a quiescent state, but in response to extrinsic stimuli, they can exit from quiescence and become reactivated to produce new neurons, so neural stem cells are considered to be a potential source for cell replacement therapy of many nervous system diseases. We characterized the expression of Ndel1 during the differentiation of neural stem cells induced by hippocampus exosomes, and assessed the effect of Ndel1 on neural stem cells differentiationMethodsHippocampal exosomes were isolated and extracted, and co-cultured exosomes with neural stem cells. Western blot, flow cytometry, and immunofluorescence analyses were used to analyze expression of neuronal markers. Further, utilizing high-throughput RNA sequencing technology, we found that nudE neurodevelopment protein 1-like 1 was significantly up-regulated in exosomes derived from denervated hippocampus, and then characterized its mechanism and function during neural stem cells differentiation by qRT-PCR, western blot, flow cytometry, and immunofluorescence analyses.ResultsOur results revealed that exosomes of denervated hippocampus promoted the differentiation of neural stem cells into neuron. Hence, we identified that nudE neurodevelopment protein 1-like 1 (Ndel1) was significantly up-regulated and highly expressed in the nervous system. In addition, we found that miR-107-3p may regulate NSCs differentiation by targeting Ndel1.ConclusionsOur results revealed that deafferentation of the hippocampal exosomes co-cultured with NSCs could promote them to differentiate into neurons. Hence, we found that miR-107-3p may regulate NSCs differentiation by targeting Ndel1. Importantly, Ndel1 enhanced spatial learning and hippocampal neurogenesis in rats after FF transection In vivo. These findings set the stage for a better understanding of neurogenesis, a process that one day may inspire new treatments for central nervous system diseases.

scholarly journals Lentiviral Vectors Mediate Efficient and Stable Gene Transfer in Adult Neural Stem Cells In Vivo

2006 ◽  
Vol 0 (0) ◽  
pp. 060801084750007
Author(s):  
Martine Geraerts ◽  
Kristel Eggermont ◽  
Pilar Hernandez-Acosta ◽  
Jose-Manuel Garcia-Verdugo ◽  
Veerle Baekelandt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Transfer ◽  
Neural Stem Cells ◽  
Lentiviral Vectors ◽  
Stable Gene ◽  
Adult Neural Stem Cells

Abstract WP94: Delayed SDF-1 Hyperexpression Promotes Neural Stem Cell Migration and Maturation without Increasing Inflammation after Ischemic Stroke in Mice

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Yaning Li ◽  
Jun Huang ◽  
Xiaosong He ◽  
Yaohui Tang ◽  
Yifan Lv ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Gene Transfer ◽  
Neural Stem Cells ◽  
Brain Atrophy ◽  
Neurological Deficits ◽  
Neuronal Function ◽  
Infarct Area

Background and purpose: SDF-1 has double-edged function after ischemic stroke. It can attract both inflammatory cells and neural stem cells (NSC). However, the action of SDF-1 in regulating neural stem cells migration and maturation during post-ischemic stroke is unclear. Here we used adeno-associated virus (AAV) to deliver SDF-1 gene into the peri-infarct area one week after permanent middle cerebral artery occlusion (MCAO) to investigate the effect of SDF-1 on endogenous NSC migration and maturation. Methods and materials: Twenty-four adult ICR male mice received AAV carrying SDF-1 or GFP gene transfer into the peri-infarct area one week after MCAO. Brain atrophy volume, neurobehavioral tests and immunohistochemistry were performed to evaluate the effects of SDF-1 on endogenous NSC migration, maturation and neuronal function repair. Results: SDF-1 was highly expressed in peri-infarct area for at least four weeks after gene transfer. Brain atrophy volume was significantly reduced in AAV-SDF-1 group compared to AAV-GFP gourp ( p <0.05). The results of neurobehavioral tests including neurological deficits and rotarod test paralleled the result of atrophy volume, with neuronal function greatly improved in AAV-SDF-1 group ( p <0.05). Immunohistology showed that the number of nestin and doublecortin positive cells in peri-infarct area was significantly increased in AAV-SDF-1 group in contrast to AAV-GFP group ( p <0.05). In addition, there was no difference in myeloperoxidase positive cells in ischemic peri-infarct area between AAV-SDF-1 and AAV-GFP group ( p >0.05). Conclusion: Our results demonstrated that SDF-1 gene therapy significantly increased NSC migration and maturation without increasing focal inflammatory response; consequently reduced brain atrophy volume and improved the neurological outcomes of animals, suggesting that delayed SDF-1 hyperexpression plays a key role in neurogenesis and neural repair. These in vivo results indicate that SDF-1 holds great potential as a stem cell chemotactic factor in the treatment of ischemic stroke.

In Vivo Transformation of Neural Stem Cells Following Transplantation in the Injured Nervous System

2009 ◽  
Vol 26 (03) ◽  
pp. 211-212 ◽  
Author(s):  
Christine Radtke ◽  
Joern Redeker ◽  
Andreas Jokuszies ◽  
Peter Vogt
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Neural Stem Cells

Engineering Biomaterials to Influence Oligodendroglial Growth, Maturation, and Myelin Production

2016 ◽  
Vol 202 (1-2) ◽  
pp. 85-101 ◽  
Author(s):  
Lauren N. Russell ◽  
Kyle J. Lampe
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Cell Growth ◽  
Neural Stem Cells ◽  
Precursor Cell ◽  
Neural Regeneration ◽  
Cell Injection ◽  
Cord Injury

Millions of people suffer from damage or disease to the nervous system that results in a loss of myelin, such as through a spinal cord injury or multiple sclerosis. Diminished myelin levels lead to further cell death in which unmyelinated neurons die. In the central nervous system, a loss of myelin is especially detrimental because of its poor ability to regenerate. Cell therapies such as stem or precursor cell injection have been investigated as stem cells are able to grow and differentiate into the damaged cells; however, stem cell injection alone has been unsuccessful in many areas of neural regeneration. Therefore, researchers have begun exploring combined therapies with biomaterials that promote cell growth and differentiation while localizing cells in the injured area. The regrowth of myelinating oligodendrocytes from neural stem cells through a biomaterials approach may prove to be a beneficial strategy following the onset of demyelination. This article reviews recent advancements in biomaterial strategies for the differentiation of neural stem cells into oligodendrocytes, and presents new data indicating appropriate properties for oligodendrocyte precursor cell growth. In some cases, an increase in oligodendrocyte differentiation alongside neurons is further highlighted for functional improvements where the biomaterial was then tested for increased myelination both in vitro and in vivo.

scholarly journals In Vivo Gene Transfer into Adult Stem Cells in Unconditioned Mice by in Situ Delivery of a Lentiviral Vector

2006 ◽  
Vol 14 (4) ◽  
pp. 514-524 ◽  
Author(s):  
D. Nicole Worsham ◽  
Todd Schuesler ◽  
Christof von Kalle ◽  
Dao Pan
Keyword(s):  
Stem Cells ◽  
Gene Transfer ◽  
Adult Stem Cells ◽  
Lentiviral Vector ◽  
In Vivo Gene Transfer

scholarly journals Robust in vivo gene transfer into adult mammalian neural stem cells by lentiviral vectors

2004 ◽  
Vol 101 (41) ◽  
pp. 14835-14840 ◽  
Author(s):  
A. Consiglio ◽  
A. Gritti ◽  
D. Dolcetta ◽  
A. Follenzi ◽  
C. Bordignon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Transfer ◽  
Neural Stem Cells ◽  
Lentiviral Vectors ◽  
In Vivo Gene Transfer
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