Allogeneic stromal cell implantation in brain tissue leads to robust microglial activation.
Although adult and embryonic stem cell-based therapy for central nervous system (CNS) injury is being developed worldwide, less attention is given to the immunological aspects of allogeneic cell implantation in the CNS. The latter is of major importance because, from a practical point of view, future stem cell-based therapy for CNS injury will likely be performed using well-characterised allogeneic stem cell populations. In this study, we aimed to further describe the immunological mechanism leading to rejection of allogeneic bone marrow-derived stromal cells (BM-SC) after implantation in murine CNS. For this, we first investigated the impact of autologous and allogeneic BM-SC on microglia activation in vitro. Although the results indicate that both autologous and allogeneic BM-SC do not activate microglia themselves in vitro, they also do not inhibit activation of microglia after exogenous stimuli in vitro. Next, we investigated the impact of allogeneic BM-SC on microglia activation in vivo. In contrast to the in vitro observations, microglia become highly activated in vivo after implantation of allogeneic BM-SC in the CNS of immune-competent mice. Moreover, our results suggest that microglia, rather than T-cells, are the major contributors to allograft rejection in the CNS.
Tambuyzer
Bart R
BR
Laboratory of Experimental Hematology, University of Antwerp, Antwerp, Belgium.
Bergwerf
Irene
I
De Vocht
Nathalie
N
Reekmans
Kristien
K
Daans
Jasmijn
J
Jorens
Philippe G
PG
Goossens
Herman
H
Ysebaert
Dirk K
DK
Chatterjee
Shyama
S
Van Marck
Eric
E
Berneman
Zwi N
ZN
Ponsaerts
Peter
P
D000818:Animals; D016026:Bone Marrow Transplantation; D001921:Brain / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D006084:Graft Rejection / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology*; D009569:Nitric Oxide / Q000032:analysis / Q000276:immunology; D033581:Stem Cell Transplantation; D017154:Stromal Cells / Q000276:immunology / Q000637:transplantation*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma