Bert J Frederich1, Valeriy Timofeyev1, Phung N Thai1, Michael J Haddad1, Adam J Poe1, Victor C Lau1, Maryam Moshref1, Anne A Knowlton2, Padmini Sirish3, Nipavan Chiamvimonvat4. 1. Division of Cardiovascular Medicine, University of California, Davis, California. 2. Division of Cardiovascular Medicine, University of California, Davis, California; US Department of Veterans Affairs, Northern California Health Care System, Mather, California. 3. Division of Cardiovascular Medicine, University of California, Davis, California. Electronic address: psirish@ucdavis.edu. 4. 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.
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. Published by Elsevier Inc.
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. Published by Elsevier Inc.
Authors: Padmini Sirish; Javier E López; Ning Li; Andrew Wong; Valeriy Timofeyev; J Nilas Young; Maryam Majdi; Ronald A Li; Huei-Sheng Vincent Chen; Nipavan Chiamvimonvat Journal: J Mol Cell Cardiol Date: 2011-10-20 Impact factor: 5.000
Authors: Padmini Sirish; Ning Li; Jun-Yan Liu; Kin Sing Stephen Lee; Sung Hee Hwang; Hong Qiu; Cuifen Zhao; Siu Mei Ma; Javier E López; Bruce D Hammock; Nipavan Chiamvimonvat Journal: Proc Natl Acad Sci U S A Date: 2013-03-14 Impact factor: 11.205