Abstract 14052: Creation of a Biological Wire Using Cell-Specific Paramagnetic Beads
Introduction: Conduction system disorders and disease-related fibrosis of the heart affect impulse propagation. Delays and blocks in impulse propagation are associated with re-entrant arrhythmias and heart block. To create a novel means of treating these disorders, we engineered a biological wire capable of bridging slow or non-conducting zones via a tissue structure created by paramagnetic beads conjugated with cell-specific antibodies (Ab).
Methods: Paramagnetic beads (8µm diameter) conjugated with γ-sarcoglycan Ab were admixed with isolated neonatal rat ventricular cardiomyocytes (NRVMs) and patterned using a superimposed magnetic field, in isolation or in apposition to other cells. To create a model of conduction block, NRVMs were plated in monolayers and mechanically interrupted along the major axis. High-resolution optical mapping using di-4-ANEPPS was utilized to record propagation of the impulse and action potential duration (APD).
Results: Isolated three-dimensional tissue structures created with NRVMs and magnets exhibited spontaneous beating rates of 82±12 BPM. Such structures could be peeled and transplanted. In order to re-establish conduction in the interrupted monolayers, paramagnetic-tagged-NRVMs in suspension were aligned perpendicular to the axis of interruption using a magnetic field to create a biological wire spanning the two halves of the culture. Prior to bridging, the two sides of an interrupted NRVM monolayer beat independently. When Ab-bead-NRVM conjugates were patterned into a spanning wire, monolayer conduction was re-established in a synchronous manner as demonstrated by voltage optical mapping. Conduction velocity through the biological wire was 0.18±0.04 mm/ms). Furthermore, action potential morphology and APD90 were similar in the biological wire (APD90=443±5ms) and the adjacent monolayers (APD90=439±12ms), p=ns.
Conclusion: Our system, using paramagnetic beads with cell-specific Ab, allowed us to engineer cardiac wires capable of re-establishing conduction between two uncoupled cell monolayers. These experiments serve as a proof of concept for a novel, flexible means to re-establish normal conduction in conditions with slow impulse propagation or conduction block.
- © 2011 by American Heart Association, Inc.