RESUMO
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.
Assuntos
Terapia Genética/métodos , Cardiopatias/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Miócitos Cardíacos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Animais , Diferenciação Celular , Movimento Celular , Células Cultivadas , Modelos Animais de Doenças , Fibroblastos/metabolismo , Fibroblastos/patologia , Cardiopatias/patologia , Masculino , Camundongos , Camundongos Knockout , Miócitos Cardíacos/patologia , Transdução de SinaisRESUMO
This report describes a method to restore an implant with irreversibly damaged internal threads. The remaining fractured post from the previous restoration was removed using a combination of an impression coping and an end-cutting bur. An elastomeric impression of the internal surface of the damaged implant, as well as the position of the adjacent implant, was made for fabrication of a new cast post and core and an implant supported 2-unit ceramometal splinted prosthesis.