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(Circulation. 2007;116:I-16 – I-23.)
© 2007 American Heart Association, Inc.

Cardiac Transplantation and Surgery for Heart Failure

Development of a Biological Ventricular Assist Device

Preliminary Data From a Small Animal Model

Yalin Yildirim, BS^*; Hiroshi Naito, MD^*; Michael Didié, MD; Bijoy Chandapillai Karikkineth, MD; Daniel Biermann, BS; Thomas Eschenhagen, MD; Wolfram-Hubertus Zimmermann, MD

From the Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Germany.

Correspondence to Wolfram-Hubertus Zimmermann, MD, Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. E-mail w.zimmermann{at}uke.uni-hamburg.de

Background— Engineered heart tissue (EHT) can be generated from cardiomyocytes and extracellular matrix proteins and used to repair local heart muscle defects in vivo. Here, we hypothesized that pouch-like heart muscle constructs can be generated by using a novel EHT-casting technology and applied as heart-embracing cardiac grafts in vivo.

Methods and Results— Pouch-like EHTs (inner/outer diameter: 10/12 mm) can be generated mainly from neonatal rat heart cells, collagen type I, and serum containing culture medium. They contain a dense network of connexin 43 interconnected cardiomyocytes and an endo-/epicardial surface lining composed of prolylhydroxylase positive cells. Pouch-like EHTs beat spontaneously and show contractile properties of native heart muscle including positive inotropic responses to calcium and isoprenaline. First implantation studies indicate that pouch-like EHTs can be slipped over uninjured adult rat hearts to completely cover the left and right ventricles. Fourteen days after implantation, EHT-grafts stably covered the epicardial surface of the respective hearts. Engrafted EHTs were composed of matrix and differentiated cardiac muscle as well as newly formed vessels which were partly donor-derived.

Conclusions— Pouch-like EHTs can be generated with structural and functional properties of native myocardium. Implantation studies demonstrated their applicability as cardiac muscle grafts, setting the stage for an evaluation of EHT-pouches as biological ventricular assist devices in vivo.

Key Words: tissue engineering • myocardium • cardiomyocyte • regeneration • transplantation