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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antibodies
  • HLA Antigens