title: Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS-976, Université Paris Diderot, Hôpital Saint-Louis, Paris, France.|HLA et Medicine, Hôpital Saint Louis, Paris, France.
authors.forename: Hocine R
authors.initials: HR
authors.lastname: Hocine
authors.affiliation: INSERM UMR 1043, Centre National Recherche Scientifique UMR 5282, Université Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: Hicham E L
authors.initials: HE
authors.lastname: Costa
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS-976, Université Paris Diderot, Hôpital Saint-Louis, Paris, France.|Cortherapix, S.L., Madrid, Spain.
authors.forename: Noemie
authors.initials: N
authors.lastname: Dam
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS-976, Université Paris Diderot, Hôpital Saint-Louis, Paris, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Giustiniani
authors.affiliation: Cortherapix, S.L., Madrid, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Palacios
authors.affiliation: Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint Louis, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Loiseau
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS-976, Université Paris Diderot, Hôpital Saint-Louis, Paris, France.
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.affiliation: Cortherapix, S.L., Madrid, Spain.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Borlado
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS-976, Université Paris Diderot, Hôpital Saint-Louis, Paris, France.|HLA et Medicine, Hôpital Saint Louis, Paris, France.|Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint Louis, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.affiliation: HLA et Medicine, Hôpital Saint Louis, Paris, France.|Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint Louis, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Suberbielle
authors.affiliation: INSERM UMR 1043, Centre National Recherche Scientifique UMR 5282, Université Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: Nabila
authors.initials: N
authors.lastname: Jabrane-Ferrat
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS-976, Université Paris Diderot, Hôpital Saint-Louis, Paris, France.|HLA et Medicine, Hôpital Saint Louis, Paris, France.
authors.forename: Reem
authors.initials: R
authors.lastname: Al-Daccak
mesh_terms: D000906:Antibodies / Q000032:analysis* / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D056724:Immunity, Humoral; D009206:Myocardium / Q000166:cytology / Q000276:immunology; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000276:immunology*
chemical_list: D000906:Antibodies; D006680:HLA Antigens