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Stem Cell Therapy for a Childhood Brain White Matter Disorder

Projectomschrijving

Hersen wittestofziekten komen op alle leeftijden voor. Op de kinderleeftijd zijn het vooral genetische ziekten, die leiden tot progressieve neurologische handicap en vroeg overlijden. Er is op dit moment geen behandeling. Wij proberen met “wittestofstamcellen” de ziekten tot staan te brengen en zo mogelijk de witte stof te genezen. Eerder uitgevoerde
stamceltransplantatiestudies zijn zeer veelbelovend. Gebruik van embryonale stamcellen is geassocieerd met ethische problemen zoals gebruik van embryo’s en afstoting van niet-lichaamseigen cellen. Om deze reden willen wij uitgaan van huidkweekcellen (fibroblasten) van de patiënten, deze reprogrammeren naar immature stamcellen, en vervolgens differentiëren naar voorlopercellen van de wittestof. De wittestofstamcellen kunnen voor transplantatie gebruikt worden. We hebben hier tot doel celtransplantatie te testen in een muismodel voor een veel voorkomende genetische wittestofziekte bij kinderen.

Producten

Titel: The effect of leukoencephalopathy Vanishing White Matter mutations on glial differentiation
Link: http://www.isscr.org/home/annual-meeting/past-future-meetings
Titel: New mouse model for Vanishing White Matter disease
Link: http://enpmeeting.org/2012/welcome.php
Auteur: Dwayne Holmes, Nicole Wolff, Marjo S. van der Knaap, Gerard Pals, and Vivi Heine
Titel: 15 Years Center for Childhood White Matter Disorders
Auteur: Prisca Leferink, Marjo S. Van der Knaap and Vivi M. Heine
Auteur: Stephanie Dooves, Niels Land, Aleid van de Kreeke, Marjo S. van der Knaap, Vivi M. Heine
Link: http://www.neurosciencecampus-amsterdam.nl/en/news-events/annual-meeting
Titel: Towards a iPSC-based glial transplantation therapy for VWM
Link: http://dsscr.nl/annual-meeting/dsscr-meeting-2013/
Auteur: Prisca Leferink, Marjo S. Van der Knaap and Vivi M. Heine
Titel: Vanishing White Matter-mutated astrocytes impair oligodendrocyte maturation in vitro
Link: http://berlin2013.gliameeting.eu/
Titel: Vanishing White Matter-mutated astrocytes inhibit oligodendrocyte progenitor cell maturation in vitro
Link: http://dsscr.nl/annual-meeting/dsscr-meeting-2015/
Auteur: Stephanie Dooves, Niels Land, Aleid van de Kreeke, Marjo S. van der Knaap, Vivi M. Heine
Titel: Stem cell derived glial cells for disease modeling and transplantation therapy for Vanishing White Matter disease
Auteur: Prisca Leferink, Stephanie Dooves, Marjo van der Knaap, Vivi Heine
Link: http://dn2016.azuleon.org/
Auteur: Stephanie Dooves, Niels Land, Aleid van de Kreeke, Marjo S. van der Knaap, Vivi M. Heine
Link: http://www.onwar.nl/pages/annual/am.htm
Auteur: Prisca Leferink, Marjo S. Van der Knaap and Vivi M. Heine
Link: http:// http://cncr.nl
Titel: Towards a iPSC-based glial transplantation therapy for VWM
Link: http://www.onwar.nl
Titel: Towards the development of a cell replacement therapy for the childhood brain white matter disorder VWM
Link: http://www.nirmresearch.nl/international.html
Titel: Vanishing White Matter-mutated astrocytes inhibit oligodendrocyte progenitor cell maturation in vitro
Link: http://www.biomedicale.parisdescartes.fr/bbn2015/?lang=en
Auteur: Stephanie Dooves, Aleid van de Kreeke, Prisca Leferink, Gerbren
Link: http://amsterdamkindersymposium.nl/
Titel: Brain White Matter Disorders and Stem Cell Therapy
Link: http://amsterdamkindersymposium.nl/
Auteur: Dwayne Holmes, Nicole Wolff, Marjo S. van der Knaap, Gerard Pals, and Vivi Heine
Link: http://www.neurosciencecampus-amsterdam.nl/en/news-agenda/annual-meeting
Auteur: Dwayne Holmes, Nicole Wolff, Marjo S. van der Knaap, Gerard Pals, and Vivi Heine
Auteur: Stephanie Dooves, Marianna Bugiani, Gerbren Jacobs, Marjo S. van der Knaap, Vivi M. Heine
Link: http://www.onwar.nl/pages/annual/am.htm
Titel: Neural stem cells: Application of iPSC technology to study neurological disorders
Link: http://www.forskningsradet.no/prognett-nevronor/Arlig_konferanse/1253987869402
Titel: Transplantation of glial precursor cells in Vanishing White Matter Disease
Link: http://www.assoela.com/
Titel: Vanishing White Matter mutated astrocytes inhibit oligodendrocyte progenitor cell maturation
Auteur: Dwayne Holmes, Nicole Wolff, Marjo S. van der Knaap, Gerard Pals, and Vivi Heine
Link: http://www.onwar.nl/pages/annual/am.htm
Auteur: Dwayne Holmes, Nicole Wolff, Marjo S. van der Knaap, Gerard Pals, and Vivi Heine
Link: http://www.amsterdamkindersymposium.nl
Auteur: Stephanie Dooves, Niels Land, Gerbren Jacobs, Marjo S. van der Knaap, Vivi M. Heine
Link: http://www.neurosciencecampus-amsterdam.nl/en/news-events/annual-meeting/
Titel: Neural stem cells
Link: http://www.nncn.de/de/bernstein-conference
Titel: How to make the right glial population for transplantation in VWM
Auteur: Prisca Leferink, Vivi Heine
Link: https://onwar-retreat.nl/
Auteur: Dwayne Holmes, Nicole Wolff, Marjo S. van der Knaap, Gerard Pals, and Vivi Heine
Link: http:// http://www.onwar.nl/pages/annual/_materiaal/ONWAR_overall_2013.pdf
Auteur: Prisca Leferink, Stephanie Dooves, Marjo S. Van der Knaap and Vivi M. Heine
Titel: Towards Stem Cell Therapy for Children with White Matter Disease
Auteur: Vivi Heine
Link: https://www.mps2016.com/en/speakers/
Titel: Cell replacement therapy for Vanishing White Matter disease
Auteur: S. Dooves, S. Bots, M.S. van der Knaap, V.M. Heine
Link: http://amsterdamkindersymposium.nl/
Auteur: Stephanie Dooves, Marjo S. van der Knaap, Vivi M. Heine
Link: http://www.onwar.nl/pages/annual/am.htm
Titel: Stamcellen voor behandeling van hersenaandoeningen
Auteur: Vivi Heine
Link: https://www.paradoks.utwente.nl/events
Auteur: Dwayne Holmes, Nicole Wolff, Marjo S. van der Knaap, Gerard Pals, and Vivi Heine
Link: http://www.neurosciencecampus-amsterdam.nl/en/news-events/annual-meeting
Titel: Stamceltherapie van wittestofziekten: waar zijn we?
Titel: The Healthy and Diseased Microenvironments Regulate Oligodendrocyte Properties
Auteur: Leferink, Prisca S., Heine, Vivi M.
Magazine: American Journal of Pathology
Titel: Leukodystrophies-5 new things
Auteur: van der Knaap, Marjo S., Wolf, Nicole I., Heine, Vivi M.
Magazine: Neurology
Titel: iPS Center - Expertise center for patient-derived nerve cells
Link: http://ipscenter.nl/
Titel: Simplified 3D protocol capable of generating early cortical neuroepithelium
Auteur: Holmes, Dwayne B., Heine, Vivi M.
Magazine: Biology Open
Titel: Cell Replacement Therapy Improves Pathological Hallmarks in a Mouse Model of Leukodystrophy Vanishing White Matter
Auteur: Dooves, Stephanie, Leferink, Prisca S., Krabbenborg, Sander, Breeuwsma, Nicole, Bots, Saskia, Hillen, Anne E.J., Jacobs, Gerbren, van der Knaap, Marjo S., Heine, Vivi M.
Magazine: Stem Cell Reports
Titel: Affected astrocytes in the spinal cord of the leukodystrophy vanishing white matter
Auteur: Leferink, Prisca S., Breeuwsma, Nicole, Bugiani, Marianna, van der Knaap, Marjo S., Heine, Vivi M.
Magazine: Glia
Titel: Bergmann glia translocation: a new disease marker for vanishing white matter identifies therapeutic effects of Guanabenz treatment
Auteur: Dooves, S., Bugiani, M., Wisse, L. E., Abbink, T. E. M., van der Knaap, M. S., Heine, V. M.
Magazine: Neuropathology and Applied Neurobiology
Titel: Stem cell therapy for white matter disorders: don’t forget the microenvironment!
Auteur: Dooves, Stephanie, van der Knaap, Marjo S., Heine, Vivi M.
Magazine: Journal of Inherited Metabolic Disease
Titel: Human and mouse iPSC-derived astrocyte subtypes reveal vulnerability in Vanishing White Matter
Auteur: Leferink, Prisca, Dooves, Stephanie, Hillen, Anne, Watanabe, Kyoko, Jacobs, Gerbren, Gasparotto, Lisa, Cornelissen-Steijger, Paulien, van der Knaap, Marjo, Heine, Vivi
Magazine: BioRxiv
Titel: Streamlined 3D Cerebellar Differentiation Protocol with Optional 2D Modification
Auteur: Holmes, Dwayne B., Heine, Vivi M.
Magazine: Journal of Visualized Experiments
Titel: Astrocytes are central in the pathomechanisms of vanishing white matter
Auteur: Dooves, Stephanie, Bugiani, Marianna, Postma, Nienke L., Polder, Emiel, Land, Niels, Horan, Stephen T., van Deijk, Anne-Lieke F., van de Kreeke, Aleid, Jacobs, Gerbren, Vuong, Caroline, Klooster, Jan, Kamermans, Maarten, Wortel, Joke, Loos, Maarten, Wisse, Lisanne E., Scheper, Gert C., Abbink, Truus E.M., Heine, Vivi M.*, van der Knaap, Marjo S.* *co-senior authors
Magazine: Journal of Clinical Investigation
Link: https://www.jci.org/articles/view/83908
Titel: Multi-level characterization of balanced inhibitory-excitatory cortical neuron network derived from human pluripotent stem cells
Auteur: Nadadhur, Aishwarya G., Emperador Melero, Javier, Meijer, Marieke, Schut, Desiree, Jacobs, Gerbren, Li, Ka Wan, Hjorth, J. J. Johannes, Meredith, Rhiannon M., Toonen, Ruud F., Van Kesteren, Ronald E., Smit, August B., Verhage, Matthijs, Heine, Vivi M.
Magazine: PLoS ONE
Titel: Patterning factors during neural progenitor induction determine regional identity and differentiation potential in vitro
Auteur: Nadadhur, Aishwarya G., Leferink, Prisca S., Holmes, Dwayne, Hinz, Lisa, Cornelissen-Steijger, Paulien, Gasparotto, Lisa, Heine, Vivi M.
Magazine: Stem Cell Research
Titel: Differential Maturation of the Two Regulated Secretory Pathways in Human iPSC-Derived Neurons
Auteur: Emperador Melero, Javier, Nadadhur, Aishwarya G., Schut, Desiree, Weering, Jan V., Heine, Vivi M., Toonen, Ruud F., Verhage, Matthijs
Magazine: PLoS ONE
Titel: Star-like cells in the brain involved in the fatal ‘Vanishing White Matter’ brain disorder
Auteur: S. Dooves, M. Bugiani, V.M. Heine, M.S. van der Knaap
Magazine: Amsterdam Science
Link: http://amsterdamscience.org/
Titel: Patient derived induced pluripotent stem cells for in vitro and in vivo modeling of neurological diseases
Link: http://enp2014.azuleon.org/programme.php

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Samenvatting van de aanvraag

“White matter disorders” have many different causes and affect patients of all ages. Childhood white matter disorders are most often genetic and progressive. Affected children have mental and motor disabilities. They need special care and education, physical therapies, rehabilitation, and special housing. They die after years of increasing handicap. The overall incidence of childhood white matter disorders is 1:1000-2000. We focus on childhood white matter disorders in general, and on the autosomal recessive leukodystrophy Vanishing White Matter Disease (VWM) in particular. Patients with VWM show increasing neurological dysfunction and die after years of illness. Neuropathologic abnormalities indicate a selective disruption of glia (both oligodendrocytes and astrocytes) in the cerebral white matter. Currently there is no treatment available. Transplantation of stem cells, primed to become glia, in early stages of the disease may halt further progression and repair (part of) the existing damage. We have generated new representative mouse models for VWM. The homozygous mice show ataxia, sporadic epileptic seizures, and die around 7 months of age. Histopathologic analysis shows lack of myelin, dysmorphic astrocytes and presence of immature cells, which are also the hallmarks of histopathology in human VWM patients. These mice offer us excellent models to test cell replacement therapies. To bring us closer towards developing personalized cell replacement therapies, we are using induced pluripotent stem (iPS) cells. If a cell replacement approach will prove to work in the human nervous system, cell transplantation therapy will become an important new strategy in treating severe neurological disorders. The research questions of this proposal are whether 1) the VWM-microenvironment affects neural stem cell differentiation and 2) transplantation of glial precursor populations into a mouse model for VWM halts progression of the disease or leads to recovery of the affected white matter.

Onderwerpen

Kenmerken

Projectnummer:
91712343
Looptijd: 100%
Looptijd: 100 %
2012
2019
Gerelateerde subsidieronde:
Projectleider en penvoerder:
Dr. V.M. Heine
Verantwoordelijke organisatie:
Amsterdam UMC - locatie VUmc