TY - JOUR
T1 - Electrotaxis of cardiac progenitor cells, cardiac fibroblasts, and induced pluripotent stem cell-derived cardiac progenitor cells requires serum and is directed via PI3′K pathways
AU - Frederich, Bert J.
AU - Timofeyev, Valeriy
AU - Thai, Phung N.
AU - Haddad, Michael J.
AU - Poe, Adam J.
AU - Lau, Victor C.
AU - Moshref, Maryam
AU - Knowlton, Anne A
AU - Sirish, Padmini
AU - Chiamvimonvat, Nipavan
PY - 2017/11/1
Y1 - 2017/11/1
N2 - Background The limited regenerative capacity of cardiac tissue has long been an obstacle to treating damaged myocardium. Cell-based therapy offers an enormous potential to the current treatment paradigms. However, the efficacy of regenerative therapies remains limited by inefficient delivery and engraftment. Electrotaxis (electrically guided cell movement) has been clinically used to improve recovery in a number of tissues but has not been investigated for treating myocardial damage. Objective The purpose of this study was to test the electrotactic behaviors of several types of cardiac cells. Methods Cardiac progenitor cells (CPCs), cardiac fibroblasts (CFs), and human induced pluripotent stem cell-derived cardiac progenitor cells (hiPSC-CPCs) were used. Results CPCs and CFs electrotax toward the anode of a direct current electric field, whereas hiPSC-CPCs electrotax toward the cathode. The voltage-dependent electrotaxis of CPCs and CFs requires the presence of serum in the media. Addition of soluble vascular cell adhesion molecule to serum-free media restores directed migration. We provide evidence that CPC and CF electrotaxis is mediated through phosphatidylinositide 3-kinase signaling. In addition, very late antigen-4, an integrin and growth factor receptor, is required for electrotaxis and localizes to the anodal edge of CPCs in response to direct current electric field. The hiPSC-derived CPCs do not express very late antigen-4, migrate toward the cathode in a voltage-dependent manner, and, similar to CPCs and CFs, require media serum and phosphatidylinositide 3-kinase activity for electrotaxis. Conclusion The electrotactic behaviors of these therapeutic cardiac cells may be used to improve cell-based therapy for recovering function in damaged myocardium.
AB - Background The limited regenerative capacity of cardiac tissue has long been an obstacle to treating damaged myocardium. Cell-based therapy offers an enormous potential to the current treatment paradigms. However, the efficacy of regenerative therapies remains limited by inefficient delivery and engraftment. Electrotaxis (electrically guided cell movement) has been clinically used to improve recovery in a number of tissues but has not been investigated for treating myocardial damage. Objective The purpose of this study was to test the electrotactic behaviors of several types of cardiac cells. Methods Cardiac progenitor cells (CPCs), cardiac fibroblasts (CFs), and human induced pluripotent stem cell-derived cardiac progenitor cells (hiPSC-CPCs) were used. Results CPCs and CFs electrotax toward the anode of a direct current electric field, whereas hiPSC-CPCs electrotax toward the cathode. The voltage-dependent electrotaxis of CPCs and CFs requires the presence of serum in the media. Addition of soluble vascular cell adhesion molecule to serum-free media restores directed migration. We provide evidence that CPC and CF electrotaxis is mediated through phosphatidylinositide 3-kinase signaling. In addition, very late antigen-4, an integrin and growth factor receptor, is required for electrotaxis and localizes to the anodal edge of CPCs in response to direct current electric field. The hiPSC-derived CPCs do not express very late antigen-4, migrate toward the cathode in a voltage-dependent manner, and, similar to CPCs and CFs, require media serum and phosphatidylinositide 3-kinase activity for electrotaxis. Conclusion The electrotactic behaviors of these therapeutic cardiac cells may be used to improve cell-based therapy for recovering function in damaged myocardium.
KW - Cardiac fibroblast
KW - Cardiac progenitor cells
KW - Electrotaxis
KW - Human induced pluripotent stem cells
KW - Phosphatidylinositide-3-kinase
KW - Soluble vascular cell adhesion molecule
UR - http://www.scopus.com/inward/record.url?scp=85032805393&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032805393&partnerID=8YFLogxK
U2 - 10.1016/j.hrthm.2017.06.038
DO - 10.1016/j.hrthm.2017.06.038
M3 - Article
C2 - 28668623
AN - SCOPUS:85032805393
VL - 14
SP - 1685
EP - 1692
JO - Heart Rhythm
JF - Heart Rhythm
SN - 1547-5271
IS - 11
ER -