In vivo autologous recellularization of a tissue-engineered heart valve: Are bone marrow mesenchymal stem cells the best candidates?

Abstract

Bone marrow stem cells, especially the mesenchymal stem cell subpopulation, have been used to create in vitro tissue-engineered heart valves. We hypothesized that autologous bone marrow cells, injected in a decellularized porcine scaffold before surgical implantation, could promote in vivo recolonization and limit valve deterioration. We thus analyzed the effects of in situ injection of autologous bone marrow mononuclear cells and of mesenchymal stem cells on the outcome of xenogenic decellularized scaffolds in a lamb model. Decellularized porcine pulmonary valves were implanted in the pulmonary artery under cardiopulmonary bypass in 14 lambs after injection in the scaffold of autologous bone marrow mononuclear cells (BMMC) group (n = 7) or of mesenchymal stem cells (MSC) group (n = 7). At 4 months, valve function was evaluated by echocardiography, and valves were explanted for macroscopic and histologic analysis. Mean transvalvular and distal gradients (millimeters of mercury) were lower in the MSC than those in the BMMC group (1.3 +/- 0.39 vs 4.24 +/- 0.91 and 4.05 +/- 1.89 vs 12.02 +/- 6.95, respectively; P < .02). Histologic examination showed significant recolonization and re-endothelialization in both groups. However, significant valve thickening and inflammatory cell infiltration were observed in the BMMC group. By contrast, valves from the MSC group displayed extracellular matrix and cell disposition close to those of native pulmonary valves. Tissue-engineered heart valves created from mesenchymal stem cells, injected directly in a decellularized xenograft scaffold, exhibited satisfactory hemodynamic and histologic aspects after 4 months. Further long-term studies are needed to demonstrate the potential of mesenchymal stem cells for clinical application in heart valve surgery.