Editors' ChoiceCardiovascular Disease

Patching up a wounded heart

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Science Translational Medicine  05 Jun 2019:
Vol. 11, Issue 495, eaax9561
DOI: 10.1126/scitranslmed.aax9561

Abstract

A bioresorbable patch provides structural support and a conduit for minimally invasive stem cell delivery to the heart after myocardial infarction.

After myocardial infarction (MI), the damaged muscle in the wall of the heart has a limited capacity to regenerate, which can lead to congestive heart failure (CHF)|. Patients developing CHF are often contraindicated for open surgery and would benefit from minimally invasive solutions that restore cardiac muscle function. Stem cell delivery has been proposed as a potential regenerative treatment. However, it is difficult to determine if stem cells provide any therapeutic benefit after injecting cells into the heart because many cells do not engraft. An alternate cell-free approach uses sleeve-like devices to reinforce the heart muscle post-MI by wrapping around the epicardium; however, this approach has not yet achieved clinical adoption.

Combining the two approaches, Dolan and colleagues created an adhesive polymer-based patch capable of delivering stem cells to the epicardium. The patch has a remotely injectable hydrogel reservoir that interfaces with the epicardial surface through a permeable membrane. Since the device is composed of bioresorbable materials, it is expected to degrade after it has performed its therapeutic function. This device can be delivered minimally invasively, although its site of attachment to the epicardium necessitates puncture of the pericardium. Treatment with the device in a porcine model showed improved left ventricle ejection fraction 14 days after MI. Surprisingly, cardiac functional improvement was observed with or without delivery of a stem cell payload via the patch.

Does the hyaluronic acid hydrogel within the patch provide a therapeutic benefit due to alterations in host cell response, or is the device mechanically stabilizing the wall of the heart and thus limiting the remodeling process post-MI? Was the timing of stem cell delivery suboptimal to achieve the paracrine effect that others have reported in similar studies? These questions will need to be addressed in subsequent longer-term follow-up studies. At minimum, this device offers a stable platform to probe the question of how to mend a broken heart.

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