Immune remodelling of stromal cell grafts in the central nervous system: therapeutic inflammation or (harmless) side-effect?
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.
Laboratory of Experimental Haematology, University of Antwerp, Antwerp, Belgium.|Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
Debbie
D
Le Blon
Laboratory of Experimental Haematology, University of Antwerp, Antwerp, Belgium.|Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
Chloé
C
Hoornaert
Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium.|Cell Systems and Cellular Imaging, Ghent University, Ghent, Belgium.
Jan R
JR
Detrez
Laboratory of Experimental Haematology, University of Antwerp, Antwerp, Belgium.|Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
Sanne
S
Bevers
Laboratory of Experimental Haematology, University of Antwerp, Antwerp, Belgium.|Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
Jasmijn
J
Daans
Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
Herman
H
Goossens
Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium.|Cell Systems and Cellular Imaging, Ghent University, Ghent, Belgium.
Winnok H
WH
De Vos
Laboratory of Experimental Haematology, University of Antwerp, Antwerp, Belgium.|Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
Zwi
Z
Berneman
Laboratory of Experimental Haematology, University of Antwerp, Antwerp, Belgium.|Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
Peter
P
Ponsaerts
D000818:Animals; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008954:Models, Biological; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation
graft-remodelling; neuroinflammation; neuroprotection; stromal cells; transplantation