Modulating the functional performance of bioengineered heart muscle using growth factor stimulation

Congestive heart failure (CHF) is a major medical challenge in developed countries. The field of cardiac tissue engineering may provide alternative treatment methods of CHF to current surgical and pharmacological therapies. We previously described a model for the formation of Bioengineered Heart Muscle (BEHM), using fibrin gel as a support matrix for primary cardiac cells during 3D construct formation. In the current study, we describe modulating the contractile properties of BEHMs utilizing clenbuterol, insulin like growth factor-1 (IGF-1), and thyroid hormone (T3), as additive factors to primary cardiac cells. We found significant changes in force production with the addition of clenbuterol (control: 95.0 +/- 32.9 mu N, clenbuterol: 201.0 +/- 15.8 mu N) and IGF-1 (control: 202.9 +/- 18 mu N, IGF-1: 272.6 +/- 19.5 mu N) was seen. Selecting IGF-1-treated BEHMs for further analysis, we found an increase in force production during extended culturing at 7, 14 days. Also, at 25 ng/mL, myosin heavy chain alpha and SERCA2 expression increased by 1.3 +/- 0.188 and 1.1 +/- 0.04 fold, respectively. Our findings provide preliminary data that can be used to produce BEHMs with higher force of contraction. Exposing BEHMs to these factors would condition the engineered muscle for possible implantation onto injured hearts without cell shock.