Vessel Plus 2022;6:[Accepted].10.20517/2574-1209.2021.149© The Author(s) 2022 Accepted Manuscript
Open AccessPerspective
Perspective on the development of a bioengineered patch to treat heart failure: rationale and proposed design of phase I clinical trial
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Steven Goldman, Jay H. Traverse, Michael R. Zile, Elizabeth Juneman, Barry Greenberg, Rosemary F. Kelly, Jen Watson Koevary, Jordan J. Lancaster
Correspondence Steven Goldman, Sarver Heart Center, Department of Medicine, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ, 85724, USA. E-mail: goldmans@shc.arizona.edu
Received: 20 Dec 2021 | Revised: 8 Mar 2022 | Accepted: 25 Mar 2022
Abstract
This perspective focuses on the development of tissue engineered (TE) cell-based therapies to treat left ventricular (LV) dysfunction and chronic heart failure (CHF). The development of induced pluripotent stem cells enabled investigators to seed or co-culture human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) alone and in combination with other cells onto bioengineered scaffolds applied to the epicardial surface of the damaged left ventricle. Using our work as an example, we show how a xenograft implant of a bioengineered scaffold embedded with human neonatal fibroblasts and seeded with hiPSC-CMs partially reversed maladaptive LV remodeling and improved LV systolic/diastolic function in an immune-competent rat model of CHF. The fibroblasts lay down an extracellular matrix and secrete growth factors that increase myocardial blood flow. This approach provides an improved cell payload that covers a larger area of the damaged left ventricle as opposed to direct cell injections into the heart or down the coronary arteries. These studies combined with ongoing studies in immune-competent Yucatan mini swine treated with the same xenograft led to the preliminary design of a proposed Phase I clinical trial that will be presented to the Federal Drug Administration. For the proposed Phase I clinical, this TE patch will be implanted onto the epicardial surface of non-immunosuppressed patients undergoing elective Coronary Artery Bypass Grafting with Ejection Fractions ≥ 20% and ≤ 45%. The primary endpoints will be adverse events/severe adverse events associated with placing the TE patch on the heart. While Phase I trials are primarily safety trials, this proposed trial is designed to obtain some potential efficacy endpoints to help with the design of future Phase II/III clinical trials. These endpoints include changes in LV remodeling that were seen in the pre-clinical animal models as well as including endpoints that focus on patient well-being. Keywords
Bioengineered patch, cardiomyocyte, cell-based therapy, fibroblast, heart failure, human induced pluripotent stem cells Cite This Article
Goldman S, Traverse JH, Zile MR, Juneman E, Greenberg B, Kelly RF, Koevary JW, Lancaster JJ. Perspective on the development of a bioengineered patch to treat heart failure: rationale and proposed design of phase I clinical trial. Vessel Plus 2022;6:[Accept]. http://dx.doi.org/10.20517/2574-1209.2021.149