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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.
Heart Rhythm 2017; 14(11):1685-1692HR

Abstract

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.

Authors+Show Affiliations

Division of Cardiovascular Medicine, University of California, Davis, California.Division of Cardiovascular Medicine, University of California, Davis, California.Division of Cardiovascular Medicine, University of California, Davis, California.Division of Cardiovascular Medicine, University of California, Davis, California.Division of Cardiovascular Medicine, University of California, Davis, California.Division of Cardiovascular Medicine, University of California, Davis, California.Division of Cardiovascular Medicine, University of California, Davis, California.Division of Cardiovascular Medicine, University of California, Davis, California; US Department of Veterans Affairs, Northern California Health Care System, Mather, California.Division of Cardiovascular Medicine, University of California, Davis, California. Electronic address: psirish@ucdavis.edu.Division of Cardiovascular Medicine, University of California, Davis, California; US Department of Veterans Affairs, Northern California Health Care System, Mather, California. Electronic address: nchiamvimonvat@ucdavis.edu.

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28668623

Citation

Frederich, Bert J., et al. "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." Heart Rhythm, vol. 14, no. 11, 2017, pp. 1685-1692.
Frederich BJ, Timofeyev V, Thai PN, et al. 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. Heart Rhythm. 2017;14(11):1685-1692.
Frederich, B. J., Timofeyev, V., Thai, P. N., Haddad, M. J., Poe, A. J., Lau, V. C., ... Chiamvimonvat, N. (2017). 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. Heart Rhythm, 14(11), pp. 1685-1692. doi:10.1016/j.hrthm.2017.06.038.
Frederich BJ, et al. 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. Heart Rhythm. 2017;14(11):1685-1692. PubMed PMID: 28668623.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2017/06/28/ PY - 2016/11/20/received PY - 2017/7/3/pubmed PY - 2018/6/19/medline PY - 2017/7/3/entrez 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 SP - 1685 EP - 1692 JF - Heart rhythm JO - Heart Rhythm VL - 14 IS - 11 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. SN - 1556-3871 UR - https://www.unboundmedicine.com/medline/citation/28668623/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1547-5271(17)30840-8 DB - PRIME DP - Unbound Medicine ER -