Search

Your search keyword '"Svendsen, Clive N."' showing total 845 results
Start Over Author "Svendsen, Clive N."
845 results on '"Svendsen, Clive N."'

202. Regulated GDNF Delivery in Vivo Using Neural Stem Cells

Author

WISCONSIN UNIV-MADISON, Svendsen, Clive N., WISCONSIN UNIV-MADISON, and Svendsen, Clive N.

Abstract

The major aim of this proposal was to establish lines of neural stem cells secreting GDNF under a regulatable promoter system which may be used for future transplant therapies for PD. The tasks of the first year have been met. We have changed from using rodent and monkey stem cells to using human stem cells (hNSC) due to better growth and infection profiles for human cells. We have shown that hNSC can be infected with lenti-GDNF. GDNF released from the cells is functional on dopamine neurons and can be switched on and off by doxycycline. We have enhanced infection rates such that over 85% of cells express GDNF. We have selected high expressing lines and shown that they can be expanded in culture for over 20 weeks without losing the ability to produce GDNF in a regulated fashion. We have performed 6-OHDA lesions in rats to induce PD and shown loss of TH expression, survival of hNSC transplanted into these animals and expression of GDNF for up to 8 weeks (this is ahead of our predicted time frame) but are currently starting in vivo regulation studies. PET analysis has shown that the lesion can be detected with imaging and we are currently optimizing this protocol for use in the more detailed studies next year. Our pilot monkey work has been delayed due to problems growing the monkey stem cells. However, we have now scheduled the first surgery using hNSC for May 2004.

Published
2004

203. Concise Review: Stem Cells for Corneal Wound Healing

Author

Saghizadeh, Mehrnoosh, Kramerov, Andrei A., Svendsen, Clive N., and Ljubimov, Alexander V.

Abstract

Corneal wound healing is a complex process that occurs in response to various injuries and commonly used refractive surgery. It is a significant clinical problem, which may lead to serious complications due to either incomplete (epithelial) or excessive (stromal) healing. Epithelial stem cells clearly play a role in this process, whereas the contribution of stromal and endothelial progenitors is less well studied. The available evidence on stem cell participation in corneal wound healing is reviewed, together with the data on the use of corneal and non‐corneal stem cells to facilitate this process in diseased or postsurgical conditions. Important aspects of corneal stem cell generation from alternative cell sources, including pluripotent stem cells, for possible transplantation upon corneal injuries or in disease conditions are also presented. StemCells2017;35:2105–2114 Schematic of corneal wounds and current stem cell treatments. Epithelial wounds (left): limbal biopsies or limbal epithelial stem cell (LESC)‐enriched cultures are used clinically. As an alternative source, iPSC‐derived LESC are examined in animals. Stromal wounds (right): mesenchymal stem cell injections are tested in animals to reduce haze and scarring. Endothelial wounds (bottom): progenitor cell injections are tested preclinically.

Published
2017
Full Text
View/download PDF

205. Human Neural Progenitor Transplantation Rescues Behavior and Reduces α‐Synuclein in a Transgenic Model of Dementia with Lewy Bodies

Author

Goldberg, Natalie R.S., Marsh, Samuel E., Ochaba, Joseph, Shelley, Brandon C., Davtyan, Hayk, Thompson, Leslie M., Steffan, Joan S., Svendsen, Clive N., and Blurton‐Jones, Mathew

Abstract

Synucleinopathies are a group of neurodegenerative disorders sharing the common feature of misfolding and accumulation of the presynaptic protein α‐synuclein (α‐syn) into insoluble aggregates. Within this diverse group, Dementia with Lewy Bodies (DLB) is characterized by the aberrant accumulation of α‐syn in cortical, hippocampal, and brainstem neurons, resulting in multiple cellular stressors that particularly impair dopamine and glutamate neurotransmission and related motor and cognitive function. Recent studies show that murine neural stem cell (NSC) transplantation can improve cognitive or motor function in transgenic models of Alzheimer's and Huntington's disease, and DLB. However, examination of clinically relevant human NSCs in these models is hindered by the challenges of xenotransplantation and the confounding effects of immunosuppressant drugs on pathology and behavior. To address this challenge, we developed an immune‐deficient transgenic model of DLB that lacks T‐, B‐, and NK‐cells, yet exhibits progressive accumulation of human α‐syn (h‐α‐syn)‐laden inclusions and cognitive and motor impairments. We demonstrate that clinically relevant human neural progenitor cells (line CNS10‐hNPCs) survive, migrate extensively and begin to differentiate preferentially into astrocytes following striatal transplantation into this DLB model. Critically, grafted CNS10‐hNPCs rescue both cognitive and motor deficits after 1 and 3 months and, furthermore, restore striatal dopamine and glutamate systems. These behavioral and neurochemical benefits are likely achieved by reducing α‐syn oligomers. Collectively, these results using a new model of DLB demonstrate that hNPC transplantation can impact a broad array of disease mechanisms and phenotypes and suggest a cellular therapeutic strategy that should be pursued. StemCellsTranslationalMedicine2017;6:1477–1490

Published
2017
Full Text
View/download PDF

206. Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits

Author

Lim, Ryan G., Quan, Chris, Reyes-Ortiz, Andrea M., Lutz, Sarah E., Kedaigle, Amanda J., Gipson, Theresa A., Wu, Jie, Vatine, Gad D., Stocksdale, Jennifer, Casale, Malcolm S., Svendsen, Clive N., Fraenkel, Ernest, Housman, David E., Agalliu, Dritan, and Thompson, Leslie M.

Abstract

Brain microvascular endothelial cells (BMECs) are an essential component of the blood-brain barrier (BBB) that shields the brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington’s disease (HD), it is not known if BMECs themselves are functionally compromised to promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction remain elusive given limitations with mouse models and post-mortem tissue to identify primary deficits. We undertook a transcriptome and functional analysis of human induced pluripotent stem cell (iPSC)-derived BMECs (iBMEC) from HD patients or unaffected controls. We demonstrate that HD iBMECs have intrinsic abnormalities in angiogenesis and barrier properties, as well as in signaling pathways governing these processes. Thus, our findings provide an iPSC-derived BBB model for a neurodegenerative disease and demonstrate autonomous neurovascular deficits that may underlie HD pathology with implications for therapeutics and drug delivery.

Published
2017
Full Text
View/download PDF

207. Ferumoxytol Labeling of Human Neural Progenitor Cells for Diagnostic Cellular Tracking in the Porcine Spinal Cord with Magnetic Resonance Imaging

Author

Lamanna, Jason J., Gutierrez, Juanmarco, Urquia, Lindsey N., Hurtig, C. Victor, Amador, Elman, Grin, Natalia, Svendsen, Clive N., Federici, Thais, Oshinski, John N., and Boulis, Nicholas M.

Abstract

We report on the diagnostic capability of magnetic resonance imaging (MRI)‐based tracking of ferumoxytol‐labeled human neural progenitor cells (hNPCs) transplanted into the porcine spinal cord. hNPCs prelabeled with two doses of ferumoxytol nanoparticles (hNPC‐FLowand hNPC‐FHigh) were injected into the ventral horn of the spinal cord in healthy minipigs. Ferumoxytol‐labeled grafts were tracked in vivo up to 105 days after transplantation with MRI. Injection accuracy was assessed in vivo at day 14 and was predictive of “on” or “off” target cell graft location assessed by histology. No difference in long‐term cell survival, assessed by quantitative stereology, was observed among hNPC‐FLow, hNPC‐FHigh, or control grafts. Histological iron colocalized with MRI signal and engrafted human nuclei. Furthermore, the ferumoxytol‐labeled cells retained nanoparticles and function in vivo. This approach represents an important leap forward toward facilitating translation of cell‐tracking technologies to clinical trials by providing a method of assessing transplantation accuracy, delivered dose, and potentially cell survival. StemCellsTranslationalMedicine2017;6:139–150

Published
2017
Full Text
View/download PDF

214. Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research

Author

Wray, S, Self, M, NINDS Parkinson's Disease iPSC Consortium, Gusella, NINDS Huntington's Disease iPSC Consortium James F., Macdonald, Marcy E., Wheeler, Vanessa C., Ross, Christopher A., Sergey, Akimov, Jamshid, Arjomand, Thompson, Leslie M., Alvin, King, Neal, Hermanowicz, Sara, Winokur, Svendsen, Clive N., Virginia, Mattis, Onorati, Marco, Elena, Cattaneo, Allen, Nicholas D., Kemp, Paul J., Kwang Soo Kim, Steven, Finkbeiner, NINDS ALS iPSC Consortium, Lewis, Pa, Taanman, Jw, Ryan, Ns, Mahoney, Cj, Liang, Y, Devine, Mj, Sheerin, Um, Houlden, H, Morris, Hr, Healy, D, Marti Masso JF, Preza, E, Barker, S, Sutherland, M, Corriveau, Ra, D'Andrea, M, Schapira, Ah, Uitti, Rj, Guttman, M, Opala, G, Jasinska Myga, B, Puschmann, A, Nilsson, C, Espay, Aj, Slawek, J, Gutmann, L, Boeve, Bf, Boylan, K, Stoessl, Aj, Ross, Oa, Maragakis, Nj, Van Gerpen, J, Gerstenhaber, M, Gwinn, K, Dawson, Tm, Isacson, O, Marder, Ks, Clark, Ln, Przedborski, Se, Finkbeiner, S, Rothstein, Jd, Wszolek, Zk, Rossor, Mn, Hardy, J., and Borlongan, Cesar V

Subjects
Neurology, Databases, Factual, Biopsy, Cellular differentiation, lcsh:Medicine, Disease, Bioinformatics, Motor Neuron Diseases, 0302 clinical medicine, Models, Neurobiology of Disease and Regeneration, 2.1 Biological and endogenous factors, Aetiology, lcsh:Science, NINDS ALS iPSC Consortium, Induced pluripotent stem cell, Psychiatry, 0303 health sciences, Multidisciplinary, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Molecular pathology, Parkinson Disease, Cell Differentiation, Medical research, Immunohistochemistry, 3. Good health, NINDS Parkinson's Disease iPSC Consortium, Autosomal Dominant, Neurological, Medicine, Medical genetics, Alzheimer's disease, Research Article, medicine.medical_specialty, General Science & Technology, Induced Pluripotent Stem Cells, Tissue Banks, Cell Line, Access to Information, Databases, 03 medical and health sciences, Genetic, Alzheimer Disease, Genetics, medicine, Humans, QH426, Biology, Factual, Cell Proliferation, 030304 developmental biology, Clinical Genetics, Stem Cell Research - Induced Pluripotent Stem Cell, Models, Genetic, business.industry, lcsh:R, Neurosciences, Fibroblasts, Stem Cell Research, medicine.disease, R1, Brain Disorders, NINDS Huntington's Disease iPSC Consortium, Geriatrics, Mutation, lcsh:Q, Dementia, Generic health relevance, Molecular Neuroscience, Nervous System Diseases, business, 2.6 Resources and infrastructure (aetiology), 030217 neurology & neurosurgery, Neuroscience
Abstract

Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community.

Published
2012
Full Text
View/download PDF

215. Gene therapy-mediated delivery of targeted cytotoxins for glioma therapeutics

Author

Candolfi, Marianela, primary, Xiong, Weidong, additional, Yagiz, Kader, additional, Liu, Chunyan, additional, Muhammad, A. K. M. G., additional, Puntel, Mariana, additional, Foulad, David, additional, Zadmehr, Ali, additional, Ahlzadeh, Gabrielle E., additional, Kroeger, Kurt M., additional, Tesarfreund, Matthew, additional, Lee, Sharon, additional, Debinski, Waldemar, additional, Sareen, Dhruv, additional, Svendsen, Clive N., additional, Rodriguez, Ron, additional, Lowenstein, Pedro R., additional, and Castro, Maria G., additional

Published
2010
Full Text
View/download PDF

224. The stem cell controversy

Author

Svendsen, Clive N

Abstract

Author(s): Clive N Svendsen [1] Renewing the stuff of life: Stem cells, ethics, and public policy Cynthia BCohen Oxford University Press, 2007 320 pp., , $35.00 In Renewing the Stuff [...]

Published
2007
Full Text
View/download PDF

241. Human i PSC-Derived Neural Progenitors Preserve Vision in an AMD-Like Model.

Author

Sahabian, Anais, Tsai, Yuchun, Girman, Sergey, Lu, Bin, Wang, Shaomei, Sareen, Dhruv, Svendsen, Clive N., and Bakondi, Benjamin

Subjects
INDUCED pluripotent stem cells, STEM cell transplantation, RETINAL degeneration
Abstract

Pluripotent stem cell-derived retinal pigment epithelial (RPE) cells are currently being tested for cell replacement in late-stage age-related macular degeneration (AMD). However, preserving vision at early-stages may also be possible. Here, we demonstrate that transplantation of neural progenitor cells (NPCs) derived from induced pluripotent stem cells (iNPCs) limits disease progression in the Royal College of Surgeons rat, a preclinical model of AMD. Grafted-iNPCs survived, remained undifferentiated, and distributed extensively in a laminar fashion in the subretinal space. Retinal pathology resulting from the accumulation of undigested photoreceptor outer segments (POS) was significantly reduced in iNPC-injected rats compared with controls. Phagosomes within grafted-iNPCs contained POS, suggesting that iNPCs had compensated for defective POS phagocytosis by host-RPE. The iNPC-treated eyes contained six to eight rows of photoreceptor nuclei that spanned up to 5 mm in length in transverse retinal sections, compared with only one row of photoreceptors in controls. iNPC treatment fully preserved visual acuity measured by optokinetic response. Electrophysiological recordings revealed that retina with the best iNPC-protected areas were 140-fold more sensitive to light stimulation than equivalent areas of contralateral eyes. The results described here support the therapeutic utility of iNPCs as autologous grafts for early-stage of AMD. S tem C ells 2015;33:2537-2549 [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

243. Astrocytes show reduced support of motor neurons with aging that is accelerated in a rodent model of ALS.

Author

Das, Melanie M. and Svendsen, Clive N.

Subjects
*ASTROCYTES, *MOTOR neurons, *BRAIN, *AGING, *LABORATORY rodents, *GLIAL cell line-derived neurotrophic factor, *SUPEROXIDE dismutase
Abstract

Astrocytes play a crucial role in supporting motor neurons in health and disease. However, there have been few attempts to understand how aging may influence this effect. Here, we report that rat astrocytes show an age-dependent senescence phenotype and a significant reduction in their ability to support motor neurons. In a rodent model of familial amyotrophic lateral sclerosis (ALS) overexpressing mutant superoxide dismutase 1 (SOD1), the rate of astrocytes acquiring a senescent phenotype is accelerated and they subsequently provide less support to motor neurons. This can be partially reversed by glial cell line–derived neurotrophic factor (GDNF). Replacing aging astrocytes with young ones producing GDNF may therefore have a significant survival promoting affect on aging motor neurons and those lost through diseases such as ALS. [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results