Concise Review: Apoptotic Cell-Based Therapies-Rationale, Preclinical Results and Future Clinical Developments

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TitreConcise Review: Apoptotic Cell-Based Therapies-Rationale, Preclinical Results and Future Clinical Developments
Type de publicationJournal Article
Year of Publication2016
AuteursSaas P, Daguindau E, Perruche S
JournalSTEM CELLS
Volume34
Pagination1464-1473
Date PublishedJUN
Type of ArticleReview
ISSN1066-5099
Mots-clésCell therapy, efferocytosis, graft-versus-host disease, inflammation, macrophages, regulatory T cells, sepsis, tolerance, transplantation
Résumé

The objectives of this review are to summarize the experimental data obtained using apoptotic cell-based therapies, and then to discuss future clinical developments. Indeed, apoptotic cells exhibit immunomodulatory properties that are reviewed here by focusing on more recent mechanisms. These immunomodulatory mechanisms are in particular linked to the clearance of apoptotic cells (called also efferocytosis) by phagocytes, such as macrophages, and the induction of regulatory T cells. Thus, apoptotic cell-based therapies have been used to prevent or treat experimental inflammatory diseases. Based on these studies, we have identified critical steps to design future clinical trials. This includes: the administration route, the number and schedule of administration, the appropriate apoptotic cell type to be used, as well as the apoptotic signal. We also have analyzed the clinical relevancy of apoptotic-cell-based therapies in experimental models. Additional experimental data are required concerning the treatment of inflammatory diseases (excepted for sepsis) before considering future clinical trials. In contrast, apoptotic cells have been shown to favor engraftment and to reduce acute graft-versus-host disease (GvHD) in different relevant models of transplantation. This has led to the conduct of a phase 1/2a clinical trial to alleviate GvHD. The absence of toxic effects obtained in this trial may support the development of other clinical studies based on this new cell therapy.

DOI10.1002/stem.2361