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Title: Umbilical cord stem cells as a candidate therapy for multiple sclerosis
Authors: DONDERS, Raf 
Advisors: Hellings, Niels
Issue Date: 2019
Abstract: This work addresses the neuroprotective and immunological properties of umbilical cord tissue-derived mesenchymal stromal cells (WJ-MSC) in the context of MS-related disease processes, both in vitro and in vivo. Additionally, this study aims to provide a better understanding of the WJ-MSC phenotype in situ, and in vitro after different isolation and culturing methods. Microarray analysis of transcriptional similarities and differences between WJ- and adult bone marrow (BM)-derived cells is performed to obtain an overview on the functional genetic signature of the cells and their mutual resemblance. Although the properties of WJ-MSC were already demonstrated to some extent, our findings provide relevant new information in the context of MS neuroinflammation, progenitor cell biology and in situ assessment of the stem cell niche. First, WJ cells were optimally isolated from umbilical cord tissue as MSCs displaying an enhanced immunological phenotype and growth potential compared to BM-MSC. A comparison of MSC from WJ and BM using full transcriptome microarray analysis further confirmed these observations, and positioned WJ cells as a distinct cell type with an intrinsic trophic support and immune modulatory genetic signature. Furthermore, we provide evidence for functional immune modulatory and neuroprotective machineries in WJ-MSC, which are shown to affect T-cell activation, APC function, neurite outgrowth, and ultimately the clinical course of an animal of MS (EAE), via mechanisms involving both cell-cell contact and the WJ secretome. In EAE, WJ-MSC are thought to interact with the local microenvironment (licensing on the spot) after i.v. administration, but only transiently improve clinical disease, although they remain viable for at least 2 weeks after transplantation. For reasons yet to determine, they were not able to halt demyelination. The exact mechanisms of action for WJ-MSC in vivo should be further detailed in additional experiments and other models, like toxin induced demyelination models, in order to get the full picture of their regenerative potential. Aside from the in vitro and in vivo characterization experiments, we performed in situ analysis of WJ tissue architecture and cell composition, using elegant and label-free imaging by multiphoton confocal microscopy. The intrinsic properties of the umbilical cord tissue allowed for detailed visualization of the cord structures and cells, based on cellular autofluorescence and detection of second harmonic generation signals from UC matrix proteins, without the need for tissue processing or antigen labeling. In the future, this tool can be used to study the different progenitor niches within the cord, likely in conjunction with current or more experimental cell labeling techniques. Collectively, we provided new and distinct information for WJ-MSC biology, that will encourage further experimentation and ultimately the translation towards clinical use of WJ-MSC from the umbilical cord, a rich but still enigmatic source of perinatal stem cells.
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Category: T1
Type: Theses and Dissertations
Appears in Collections:PhD theses
Research publications

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