Early inflammatory responses following cell grafting in the CNS trigger activation of the sub-ventricular zone: a proposed model of sequential cellular events.
Creators
- 1. Experimental Cell Transplantation Group, Laboratory of Experimental Hematology, University of Antwerp, 2610 Wilrijk, Belgium; Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, 2610 Wilrijk, Belgium and BioImaging Laboratory, University of Antwerp, 2610 Wilrijk, Belgium.
- 2. Center for Statistics, I-Biostat, Hasselt University, 3950 Diepenbeek, Belgium.
- 3. Experimental Cell Transplantation Group, Laboratory of Experimental Hematology, University of Antwerp, 2610 Wilrijk, Belgium and Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, 2610 Wilrijk, Belgium.
- 4. Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, 2610 Wilrijk, Belgium.
- 5. Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, 2610 Wilrijk, Belgium; Center for Statistics, I-Biostat, Hasselt University, 3950 Diepenbeek, Belgium and Centre for Health Economic Research and Modeling Infectious Diseases (Chermid), University of Antwerp, 2610 Wilrijk, Belgium.
- 6. BioImaging Laboratory, University of Antwerp, 2610 Wilrijk, Belgium.
Description
While multiple rodent pre-clinical studies, and to a lesser extent human clinical trials, claim the feasibility, safety and potential clinical benefit of cell grafting in the central nervous system (CNS), currently only little convincing knowledge exists regarding the actual fate of the grafted cells and their effect on the surrounding environment (or vice versa). Our preceding studies already indicated that only a minor fraction of the initially grafted cell population survives the grafting process, while the surviving cell population becomes invaded by highly activated microglia/macrophages and surrounded by reactive astrogliosis. In the current study, we further elaborate on early cellular and inflammatory events following syngeneic grafting of eGFP+ mouse embryonic fibroblasts (mEFs) in the CNS of immune-competent mice. Based on obtained quantitative histological data, we here propose a detailed mathematically-derived working model that sequentially comprises hypoxia-induced apoptosis of grafted mEFs, neutrophil invasion, neo-angiogenesis, microglia/macrophage recruitment, astrogliosis and eventually survival of a limited number of grafted mEFs. Simultaneously, we observed that the cellular events following mEF grafting activates the sub-ventricular zone neural stem and progenitor cell compartment. This proposed model therefore further contributes to our understanding of cell graft-induced cellular responses, and will eventually allow for successful manipulation of this intervention.
Files
Praet_Cell_Transplant_2014-P07-AAM.pdf
Files
(1.1 MB)
Name | Size | Download all |
---|---|---|
md5:54c15c7d28a448d9fe25ffb360cd7465
|
1.1 MB | Preview Download |