Key result
Stem cell-seeded pulmonary valves cause progressive RV failure and fibrotic overgrowth in sheep vs unseeded valves.
Why the study?
An ideal heart valve replacement may be acellular valve root scaffolds seeded with autologous stem cells, but their effects have not been tested in vivo.
Does seeding acellular xenogeneic pulmonary valves with autologous stem cells improve valve function and tissue regeneration in a sheep model?
Does seeding acellular xenogeneic pulmonary valves with autologous stem cells improve valve function and tissue regeneration in a sheep model?
Seeding acellular xenogeneic pulmonary valves with autologous adipose-derived stem cells was not conducive to tissue regeneration and led to right ventricular failure in a sheep model, whereas unseeded acellular valves performed well.
Supports preclinical valve engineering; leaves open human translation pending controlled trials.
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.
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Harpa et al. (2015) studied Pulmonary heart valve replacement (n=12). Autologous adipose-derived stem cell (ADSC) seeded acellular porcine pulmonary valves vs. Unseeded acellular porcine pulmonary valves was evaluated on Valve function and right ventricular failure (assessed by echocardiography and histology). Seeding acellular porcine pulmonary valves with autologous adipose-derived stem cells led to progressive right ventricular failure and extensive fibrotic overgrowth in sheep, whereas unseeded valves maintained normal function.
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