Injectable bioartificial tissue for cell transfer and cardiac repair: Embryonic stem cells for tissue engineering

Background: Most of the plenty tissue engineering approaches to restore injured heart muscle result in distorsion of left ventricular geometry. In the present study, we suggest seeding labeled embryonic stem cells in a liquid matrix for transplantation into the injured heart and promote functional recovery. Methods: Early GFP-positive mouse embryonic stem cells were seeded in Matrigel while at 15°C (liquid condition). In a rat heterotopic heart transplant model an intramural left ventricular pouch was fashioned after ligation of the Left Anterior Descending artery (LAD). The bioartificial mixture (0.125 ml) was then injected in the resulting infarcted area within the pouch and solidified after a few minutes after transplantation (37°C). Echocardiography was performed prior to animal sacrifice to assess fractional shortening (FS) in sham operated rats, infarcted controls or matrix recipients alone and to visualize left ventricular geometry. The consecutively harvested hearts were stained for GFP and cardiac markers (connexin 43, α-sarcomeric actin). Tissue remodeling was evaluated by trichrome and H&E stains. We used confocal microscopy for colocalization studies. Results: The Matrigel-cell mixture solidified well and formed a sustained structure within the injured area. It was microscopically homogenous and helped retain cardiac left ventricular geometry, thereby preventing ventricular wall thinning. The inoculated cells partially formed viable grafts which partially differentiated to a cardiotypical progeny, expressing connexin 43 and α-sarcomeric actin. Cellular atypia and nuclear polymorphism were only minor but still present. Despite the non-working model, fraction shortening and regional contractility were better in animals which received bioartificial tissue grafts. Conclusions: The use of bioartificial myocardial tissue equivalents which are in an adaptable physical condition constitutes a powerful new approach to restore injured heart muscle without distorting its geometry and structure. Embryonic stem cells - optimally a committed progeny - are a potent substrate for large scale transfer of bioartificial tissue.