TY - JOUR
T1 - Glycosylated cell surface markers for the isolation of human cardiac progenitors
AU - Moerkamp, A.T.
AU - Leung, H.W.
AU - Bax, N.A.M.
AU - Holst, S.
AU - Lodder, K.
AU - Berends, T.
AU - Dingenouts, C.K.E.
AU - Choo, A.
AU - Smits, A.M.
AU - Goumans, M.J.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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.
KW - glycosylation
KW - GRP78
KW - human cardiac progenitor cells
KW - monoclonal antibodies
KW - multipotent
KW - PECAM1
UR - http://www.scopus.com/inward/record.url?scp=85032455589&partnerID=8YFLogxK
U2 - 10.1089/scd.2017.0048
DO - 10.1089/scd.2017.0048
M3 - Article
C2 - 28891400
AN - SCOPUS:85032455589
SN - 1547-3287
VL - 26
SP - 1552
EP - 1565
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 21
ER -