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Sci Rep. 2017 Jan 24;7:41125. doi: 10.1038/srep41125.

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

Author information

1
Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS-976, Université Paris Diderot, Hôpital Saint-Louis, Paris, France.
2
HLA et Medicine, Hôpital Saint Louis, Paris, France.
3
INSERM UMR 1043, Centre National Recherche Scientifique UMR 5282, Université Toulouse III Paul Sabatier, Toulouse, France.
4
Cortherapix, S.L., Madrid, Spain.
5
Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint Louis, Paris, France.

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.

PMID:
28117403
PMCID:
PMC5259698
DOI:
10.1038/srep41125
[Indexed for MEDLINE]
Free PMC Article

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