Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells.

Fiche publication


Date publication

janvier 2017

Journal

Scientific reports

Auteurs

Membres identifiés du Cancéropôle Est :
Pr BENSUSSAN Armand


Tous les auteurs :
Hocine HR, Costa HE, Dam N, Giustiniani J, Palacios I, Loiseau P, Bensussan A, Borlado LR, Charron D, Suberbielle C, Jabrane-Ferrat N, Al-Daccak R

Résumé

Allogeneic human cardiac-derived stem/progenitor cells (hCPC) are currently under clinical investigation for cardiac repair. While cellular immune response against allogeneic hCPC could be part of their beneficial-paracrine effects, their humoral immune response remains largely unexplored. Donor-specific HLA antibodies (DSA-HLA-I/DSA-HLA-II), primary elements of antibody-mediated allograft injury, might present an unidentified risk to allogeneic hCPC therapy. Here we established that the binding strength of anti-HLA monoclonal antibodies delineates hCPC proneness to antibody-mediated injury. In vitro modeling of clinical setting demonstrated that specific DSA-HLA-I of high/intermediate binding strength are harmful for hCPC whereas DSA-HLA-II are benign. Furthermore, the Luminex-based solid-phase assays are suitable to predict the DSA-HLA risk to therapeutic hCPC. Our data indicate that screening patient sera for the presence of HLA antibodies is important to provide an immune-educated choice of allogeneic therapeutic cells, minimize the risk of precipitous elimination and promote the allogeneic reparative effects.

Mots clés

Antibodies, analysis, HLA Antigens, immunology, Histocompatibility Testing, Humans, Immunity, Humoral, Myocardium, cytology, Stem Cell Transplantation, methods, Stem Cells, immunology

Référence

Sci Rep. 2017 01 24;7:41125