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Immune remodelling of stromal cell grafts in the central nervous system: therapeutic inflammation or (harmless) side-effect?

Authors
  • Le Blon, Debbie1, 2
  • Hoornaert, Chloé1, 2
  • Detrez, Jan R3, 4
  • Bevers, Sanne1, 2
  • Daans, Jasmijn1, 2
  • Goossens, Herman2
  • De Vos, Winnok H3, 4
  • Berneman, Zwi1, 2
  • Ponsaerts, Peter1, 2
  • 1 Laboratory of Experimental Haematology, University of Antwerp, Antwerp, Belgium. , (Belgium)
  • 2 Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium. , (Belgium)
  • 3 Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium. , (Belgium)
  • 4 Cell Systems and Cellular Imaging, Ghent University, Ghent, Belgium. , (Belgium)
Type
Published Article
Journal
Journal of Tissue Engineering and Regenerative Medicine
Publisher
Wiley (John Wiley & Sons)
Publication Date
Oct 01, 2017
Volume
11
Issue
10
Pages
2846–2852
Identifiers
DOI: 10.1002/term.2188
PMID: 27320821
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Over the past two decades, several cell types with fibroblast-like morphology, including mesenchymal stem/stromal cells, but also other adult, embryonic and extra-embryonic fibroblast-like cells, have been brought forward in the search for cellular therapies to treat severe brain injuries and/or diseases. Although current views in regenerative medicine are highly focused on the immune modulating and regenerative properties of stromal cell transplantation in vivo, many open questions remain regarding their true mode of action. In this perspective, this study integrates insights gathered over the past 10 years to formulate a unifying model of the cellular events that accompany fibroblast-like cell grafting in the rodent brain. Cellular interactions are discussed step-by-step, starting from the day of implantation up to 10 days after transplantation. During the short period that precedes stable settlement of autologous/syngeneic stromal cell grafts, there is a complex interplay between hypoxia-mediated cell death of grafted cells, neutrophil invasion, microglia and macrophage recruitment, astrocyte activation and neo-angiogenesis within the stromal cell graft site. Consequently, it is speculated that regenerative processes following cell therapeutic intervention in the CNS are not only modulated by soluble factors secreted by grafted stromal cells (bystander hypothesis), but also by in vivo inflammatory processes following stromal cell grafting. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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