Implantation of a Tissue-engineered Heart Valve from Human Fibroblasts Exhibiting Short Term Function in the Sheep Pulmonary Artery
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We have previously demonstrated the feasibility of fabricating a fibrin-based tissue-engineered heart valve (TEHV) using neonatal human dermal fibroblasts (nhDF), including leaflets with structural and mechanical anisotropy similar to native leaflets. The aim here was to evaluate the performance of this TEHV in a pilot study using the sheep model. Bi-leaflet TEHV were conditioned in a cyclic stretching bioreactor, then implanted within a polymeric sleeve interpositionally into the pulmonary artery of four sheep, with the pulmonary valve either left intact or rendered incompetent. Heparin and immunosuppression were administered for the duration. Echocardiography was performed at implantation and at 4 and 8 weeks. Explants were examined histologically, biochemically, and mechanically. In all sheep, echocardiography at implantation showed coapting leaflets, with minimal valve regurgitation and no turbulence. Orifice area and pressure gradients at systole approached the native pulmonary valve values. Echocardiography at 4 weeks revealed both leaflets functional with moderate regurgitation and turbulence in three sheep; in one sheep, only one leaflet was evident. Explanted leaflets had thickness and tensile properties comparable to the implanted leaflets. There was extensive endothelialization of the root lumenal surface. In the two sheep continued to 8 weeks, only one shortened leaflet remained in both cases. Immunocytochemistry indicated this was due to sustained tissue contraction caused by the nhDF and not by the invading host cells, which included a subpopulation consistent with bone marrow-derived cells. Short-term success was thus achieved in terms of excellent valve function at implantation and some valve function for at least 4 weeks; however, an apparent progressive tissue contraction needs to be resolved for long-term success.
KeywordsTissue-engineering Heart valve Fibrin Fibroblast Ovine
The authors acknowledge Naomi Ferguson, Cary Valley, Stephen Stephens, Ricky Chow, and Linisia Wahyudi for technical assistance. Funding was provided by the National Institutes of Health (USA) BRP HL71538 to R.T.T.
Conflict of interest
The authors have no conflicts of interest with the reported study to disclose.
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