Induced pluripotent stem cells: therapeutic potential for multiple sclerosis

Czepiel, M., 2015, [S.l.]: [S.n.]. 181 p.

Research output: ThesisThesis fully internal (DIV)Academic

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  • Title and contents

    Final publisher's version, 355 KB, PDF-document

  • Chapter 1

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  • Chapter 2

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  • Chapter 3

    Final publisher's version, 6 MB, PDF-document

  • Chapter 4

    Final publisher's version, 11 MB, PDF-document

  • Chapter 5

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  • Chapter 6

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  • Chapter 7

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  • Chapter 8

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  • Complete dissertation

    Final publisher's version, 36 MB, PDF-document

  • Propositions

    Final publisher's version, 26 KB, PDF-document

  • Marcin Czepiel
Multiple Sclerosis (MS) is a devastating disease of the central nervous system (CNS) characterized by loss of the insulating myelin layer around axons due to inflammatory attacks. Loss of myelin in MS not only disrupts the rapid signal transmission along axons, but also deprives axons of essential nutrition and protection provided by myelin. Prolonged absence of such protection makes axons vulnerable to all kinds of toxic environmental influences, eventually leading to degeneration of neurons provoking the most severe neurological deficits in MS. Reducing or preferably completely preventing neurodegeneration in MS remains the main challenge for new treatment methods; establishing fast restoration of the myelin sheaths (remyelination) seems a logical and appropriate approach. However, while considerable progress has been made in recent years in therapies that can significantly reduce the severity and frequency of inflammatory attacks in MS patients, there is no therapeutic strategy for MS aimed at the efficient remyelination of axons. Intracerebral transplantation of myelin-forming cells – oligodendrocytes – has been shown a successful approach in various animal models of MS. However, such an approach was not possible for MS patients because of the lack of a suitable source of autologous (“own”) oligodendrocytes. The solution to this problem was provided by the discovery of induced pluripotency in 2006: ordinary somatic cells, like skin fibroblasts, could be reprogrammed into so-called induced pluripotent stem cells (iPSCs), embryonic stem cell-like cells with the capacity to proliferate unlimitedly and to differentiate into any cell type of the body. iPSCs can thus serve as a virtually inexhaustible autologous (!) source for transplantable myelin-forming cells. This thesis describes research on the potential use of iPSCs as a source for oligodendrocytes to be used in a novel cell-based remyelination and neuroprotection therapy of MS.
Translated title of the contributionGeïnduceerde pluripotente stamcellen: therapeutisch potentieel voor multiple sclerose
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Boddeke, Hendrikus, Supervisor
  • Copray, Joseph, Co-supervisor
  • Amor, S, Assessment committee, External person
  • Brück, W. (Wolfgang), Assessment committee, External person
  • van der Knaap, M. S., Assessment committee, External person
Award date12-Jan-2015
Place of Publication[S.l.]
Print ISBNs978-90-367-7540-3
Electronic ISBNs978-90-367-7539-7
Publication statusPublished - 2015

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