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

Yen-Chih Huang1, Luda Khait, Ravi K Birla

  • 1Deparment of Biomedical Engineering, The University of Michigan, Ann Arbor, MI 48109, USA.

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Bioengineered Heart Muscle (BEHM) shows enhanced contraction force with growth factors like IGF-1. This cardiac tissue engineering approach may improve treatments for congestive heart failure (CHF).

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Area of Science:

  • Biomaterials and Tissue Engineering
  • Cardiovascular Research
  • Regenerative Medicine

Background:

  • Congestive heart failure (CHF) presents a significant clinical challenge, driving the need for innovative therapeutic strategies.
  • Cardiac tissue engineering offers a promising alternative to traditional treatments for CHF.
  • Previous work established a model for Bioengineered Heart Muscle (BEHM) using fibrin gel and primary cardiac cells.

Purpose of the Study:

  • To investigate the modulation of contractile properties in BEHMs.
  • To evaluate the effects of specific growth factors—clenbuterol, insulin-like growth factor-1 (IGF-1), and thyroid hormone (T3)—on BEHM function.
  • To determine the potential of these factors in enhancing BEHM contractility for future implantation.

Main Methods:

  • BEHMs were cultured with the addition of clenbuterol, IGF-1, and T3.
  • Contractile force production of BEHMs was measured.
  • Gene expression of key proteins, including myosin heavy chain alpha and SERCA2, was analyzed in IGF-1 treated BEHMs.
  • Extended culturing was performed to assess long-term effects.

Main Results:

  • Clenbuterol and IGF-1 significantly increased BEHM force production compared to controls.
  • IGF-1 treatment led to sustained increases in force production over 7 and 14 days of culturing.
  • Myosin heavy chain alpha and SERCA2 expression levels were elevated in BEHMs treated with IGF-1 at 25 ng/mL.
  • These findings suggest that growth factor treatment can enhance the mechanical properties of engineered cardiac tissue.

Conclusions:

  • Growth factor supplementation, particularly IGF-1, can significantly enhance the contractile force of Bioengineered Heart Muscle (BEHM).
  • These findings provide a basis for developing engineered cardiac tissues with improved functional capacity.
  • Conditioning BEHMs with these factors may prepare them for successful implantation onto damaged hearts, potentially reducing cell shock.