Glycosylated Cell Surface Markers for the Isolation of Human Cardiac Progenitors

Stem Cells Dev. 2017 Nov 1;26(21):1552-1565. doi: 10.1089/scd.2017.0048. Epub 2017 Oct 17.

Abstract

The aim of stem cell therapy after cardiac injury is to replace damaged cardiac tissue. Human cardiac progenitor cells (CPCs) represent an interesting cell population for clinical strategies to treat cardiac disease and human CPC-specific antibodies would aid in the clinical implementation of cardiac progenitor-based cell therapy. However, the field of CPC biology suffers from the lack of human CPC-specific markers. Therefore, we raised a panel of monoclonal antibodies (mAb) against CPCs. Of this panel of antibodies, we show that mAb C1096 recognizes a progenitor-like population in the fetal and adult human heart and partially colocalize with reported CPC populations in vitro. Furthermore, mAb C1096 can be used to isolate a multipotent progenitor population from human heart tissue. Interestingly, the two lead candidates, mAb C1096 and mAb C19, recognize glycosylated residues on PECAM1 (platelet and endothelial cell adhesion molecule 1) and GRP78, respectively, and de-N-glycosylation significantly abolishes their binding. Thereby, this report describes new clinically applicable antibodies against human CPCs, and for the first time demonstrates the importance of glycosylated residues as CPCs specific markers.

Keywords: GRP78; PECAM1; glycosylation; human cardiac progenitor cells; monoclonal antibodies; multipotent.

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antigens, Surface / immunology
  • Cells, Cultured
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / immunology
  • Endoplasmic Reticulum Chaperone BiP
  • Glycosylation
  • Heat-Shock Proteins / immunology*
  • Humans
  • Myoblasts, Cardiac / cytology*
  • Myoblasts, Cardiac / immunology
  • Platelet Endothelial Cell Adhesion Molecule-1 / immunology*
  • Protein Processing, Post-Translational

Substances

  • Antibodies, Monoclonal
  • Antigens, Surface
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Platelet Endothelial Cell Adhesion Molecule-1