Open AccessMinimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells
Author(s) -
Hocine R. Hocine,
Hicham El Costa,
Noémie Dam,
Jérôme Giustiniani,
Itziar Palacios,
Pascale Loiseau,
Armand Bensussan,
Luis R. Borlado,
Dominique Charron,
Caroline Suberbielle,
Nabila JabraneFerrat,
Reem Al-Daccak
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep41125
Subject(s) - human leukocyte antigen , progenitor cell , immune system , monoclonal antibody , immunology , antibody , sensitization , stem cell , medicine , antigen , biology , microbiology and biotechnology
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.