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Title: | Early Inflammatory Responses Following Cell Grafting in the CNS Trigger Activation of the Subventricular Zone: A Proposed Model of Sequential Cellular Events | Authors: | Praet, Jelle SANTERMANS, Eva Daans, Jasmijn Le Blon, Debbie Hoornaert, Chloe Goossens, Herman HENS, Niel Van der Linden, Annemie Berneman, Zwi Ponsaerts, Peter |
Issue Date: | 2015 | Publisher: | COGNIZANT COMMUNICATION CORP | Source: | CELL TRANSPLANTATION, 24 (8), p. 1481-1492 | Abstract: | While multiple rodent preclinical 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 immunocompetent 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, neoangiogenesis, 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 subventricular 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. | Notes: | [Praet, Jelle; Daans, Jasmijn; Le Blon, Debbie; Hoornaert, Chloe; Berneman, Zwi; Ponsaerts, Peter] Univ Antwerp, Expt Cell Transplantat Grp, Lab Expt Hematol, B-2610 Antwerp, Belgium. [Praet, Jelle; Daans, Jasmijn; Le Blon, Debbie; Hoornaert, Chloe; Goossens, Herman; Hens, Niel; Berneman, Zwi; Ponsaerts, Peter] Univ Antwerp, Vaccine & Infect Dis Inst Vaxinfectio, B-2610 Antwerp, Belgium. [Praet, Jelle; Van der Linden, Annemie] Univ Antwerp, BioImaging Lab, B-2610 Antwerp, Belgium. [Santermans, Eva; Hens, Niel] Hasselt Univ, Ctr Stat, I Biostat, Diepenbeek, Belgium. [Hens, Niel] Univ Antwerp, Chermid, B-2610 Antwerp, Belgium. | Keywords: | cell transplantation; graft apoptosis; immune response; angiogenesis; cell proliferation;Cell transplantation; Graft apoptosis; Immune response; Angiogenesis; Cell proliferation | Document URI: | http://hdl.handle.net/1942/19895 | ISSN: | 0963-6897 | e-ISSN: | 1555-3892 | DOI: | 10.3727/096368914X682800 | ISI #: | 000359878900006 | Rights: | Copyright © 2015 Cognizant Comm. Corp. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2016 |
Appears in Collections: | Research publications |
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File | Description | Size | Format | |
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praet 1.pdf Restricted Access | Published version | 1.28 MB | Adobe PDF | View/Open Request a copy |
peer.pdf | Peer-reviewed author version | 1.14 MB | Adobe PDF | View/Open |
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