Marius Harpa, Ionela Movileanu, Leslie Sierad, Ovidiu Cotoi, Horațiu Suciu, Terezia Preda, Dan Nistor, Carmen Sircuța, Klara Brânzaniuc, Radu Deac, Simona Gurzu, Lucian Harceaga, Peter Olah, Dan Simionescu, Michael Dandel and Agneta Simionescu
Marius Mihai Harpa, Ionela Movileanu, Leslie Neil Sierad, Ovidiu Simion Cotoi, Horatiu Suciu, Carmen Sircuta, Terezia Preda, Dan Nistor, Klara Branzaniuc, Radu Deac, Michael Dandel, Simona Gurzu, Lucian Harceaga, Peter Olah, Agneta Simionescu and Dan Simionescu
Background: We hypothesized that an ideal heart valve replacement would be acellular valve root scaffolds seeded with autologous stem cells. To test this hypothesis, we prepared porcine acellular pulmonary valves, seeded them with autologous adipose derived stem cells (ADSCs) and implanted them in sheep and compared them to acellular valves.
Methods: Fresh porcine pulmonary valve roots were decellularized with detergents and enzymes. ADSCs were isolated from subdermal fat and injected within the acellular cusps. Valves were then implanted in an extra-anatomic pulmonary position as RV to PA shunts: Group A (n=6) consisted of acellular valves and Group B (n=6) of autologous stem cell-seeded acellular xenografts. Sheep were followed up for 6 months by echocardiography and histologic analysis was performed on explanted valves.
Results: Early evolution was favorable for both groups. All Group A animals had physiologic growth without any signs of heart failure and leaflets were found with preserved structure and mobility, lacking signs of thrombi, inflammation or calcification. Group B sheep however expressed signs of right ventricle failure starting at one month, accompanied by progressive regurgitation and right ventricle dilatation, and the leaflets were found covered with host tissue. No cells were found in any Group A or B explants.
Conclusions: Acellular stabilized xenogeneic pulmonary valves are reliable, stable, non-immunogenic, non-thrombogenic and non-calcifying scaffolds with excellent hemodynamics. Seeding these scaffolds with autologous ADSCs was not conducive to tissue regeneration. Studies aimed at understanding these novel observations and further harnessing the potential of stem cells are ongoing.
Ionela Movileanu, Marius Harpa, Klara Branzaniuc, Horatiu Suciu, Ovidiu S. Cotoi, Peter Olah and Dan Simionescu
Objective: To describe a particular harvesting procedure for isolating intact porcine aortic heart valve roots as potential sources for biologic scaffolds.
Methods: Fresh porcine hearts were brought to the Tissue Engineering and Regenerative Medicine Laboratory at the University of Medicine and Pharmacy in Targu Mures. The aortic roots were extracted from the porcine hearts by anatomical dissection. For this purpose, we used a basic surgical instrument kit. This initial phase was the first step in obtaining acellular extracellular matrix as a biologic scaffold material.
Results: Aortic roots were isolated with preservation of the ascending aorta as well as the intact aortic sinus and coronaries together with the adjacent myocardial tissue and anterior leaflet of the mitral valve. This approach allowed for safe mounting of roots into mounting rings for perfusion decellularization.
Conclusions: The described procedure is a feasible protocol for obtaining intact biological valvular scaffolds from porcine hearts. Reduced requirements regarding tools and personnel underline the easiness of aortic root harvesting using this particular procedure.