Editors' ChoiceCardiology

Cyborg fibroblasts: Cardiac pacemakers of the future?

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Science Translational Medicine  30 Oct 2019:
Vol. 11, Issue 516, eaaz3722
DOI: 10.1126/scitranslmed.aaz3722

Abstract

Cardiac fibroblasts with internalized silicon nanowires can be stimulated with laser light to electrically pace neighboring cardiac myocytes.

Controlling the electrical activity of the heart has historically required a direct interface with an electronic device, such as an artificial pacemaker. However, conventional artificial pacemakers are synthetic and rigid devices that can damage cardiac muscle. Electronic devices also have finite battery life and do not grow with the patient, a major concern for pediatric patients. To overcome these problems, researchers have genetically modified mammalian cells to express light-sensitive ion channels, such as those found in algae. When cardiac muscle cells express these channels, their electrical activity can be controlled using light, removing the need for a direct interface with an electronic device. However, modifying the genetic material of cells in patients is a complex process and raises safety concerns.

Rotenberg et al. developed a completely new approach for electrically pacing heart tissue by first exposing cardiac fibroblasts to silicon nanowires, which are naturally internalized by cells. These hybrid nanowire-fibroblasts were then grown with cardiac muscle cells in culture and exposed to localized pulses of laser light, which induced a small current in the silicon nanowires. This current caused electrical activation of not only the fibroblasts but also their neighboring cardiac myocytes due to the formation of electrical junctions between these cells in culture.

Next, the researchers tested if this strategy would work in intact heart tissue by injecting hybrid nanowire-fibroblasts or bare nanowires into rat hearts. Unlike the bare nanowires, the hybrid nanowire-fibroblasts did not trigger an immune reaction, demonstrating a promising safety profile. However, the researchers could not robustly pace cardiac myocytes by photostimulating adjacent hybrid nanowire-fibroblasts. This is likely because electrical junction formation between these two cell types within the heart is relatively low, a challenge that will need to be addressed for this technology to translate to the clinic. Despite this limitation, the ability to someday control the electrical activity of the heart without needing to genetically modify cells or directly interface cardiac tissue with an electronic device would be a major advance for treating patients with cardiac rhythm disorders.

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