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J Thorac Cardiovasc Surg 2008;135:1407
© 2008 The American Association for Thoracic Surgery

Letter to the Editor

Reply to the Editor

André Vincentelli, MD, PhDa,b, Francis Juthier, MDa,b, Brigitte Jude, MD, PhDa,b

a Centre Hospitalier Régional, Universitaire de Lille, Pôle de Chirurgie Cardiovasculaire, Institut d'Hématologic Transfusion, Lille, F-59037 France
b Université de de Lille 2, EA 2693, Faculté de Médecine, Lille, F-59045 France

We thank Drs Di Marco and Gerosa for considering that injection of mesenchymal stem cells (MSCs) in decellularized scaffolds before in vivo implantation represents an innovative concept in the valvular field, and we completely agree that this concept requires a careful validation. However, they expressed some concern about our conclusion that bone marrow–derived mononuclear cell injection induced a structural deterioration of the scaffold and that MSCs induced a protective effect.

We believe that the observation of a deleterious effect of bone marrow–derived mononuclear cells is an interesting point because these cells had never been tested in the field of valve tissue engineering, whereas they are currently used in clinical assays in the field of myocardial failure. Also, we agree that endothelialization and scaffold recolonization are 2 distinct processes that do not always take place together. However, Bertiplaglia and colleagues1Go have demonstrated that 2 weeks after in vitro interstitial cell seeding into decellularized leaflets, grafted cells were found penetrating the decellularized scaffold and expressed various immunologic differentiation patterns, such as fibroblasts, myofibroblasts, smooth muscle cells, and also endothelial cells. Similarly, we observed a significant recolonization after injection of MSCs, and moreover, as stated in our article, pulmonary leaflets exhibited a typical organization in 3 layers (ie, fibrosa, spongiosa, and ventricularis) in each animal of the MSC group.2Go

Finally, several lines of evidence indicate that in vivo recellularization of valve scaffolds is no longer a "nonvalidated route." In a previous work we demonstrated evidence of spontaneous recellularization of a decellularized valve.3Go Such results were emphasized by Dohmen and coworkers4Go comparing in vitro seeded and nonseeded valves implanted in sheep. After 6 months, valves from both groups exhibited full recolonization of the leaflets, with comparable hemodynamic behavior and valve remodeling.

We recognize that further studies are needed to compare spontaneous recolonization of an appropriated scaffold and the effects of in situ injection of autologous cells. Also, we have to investigate how injected autologous MSCs improve in situ recolonization by myofibroblasts and endothelial cells or improve host cell migration. However, the challenge seems now to understand and to favor in vivo, rather than in vitro, valve scaffold recolonization.

References

  1. Bertipaglia B, Ortolani F, Petrelli L, Gerosa G, Spina M, Pauletto P, et al. Cell characterization of porcine aortic valve and decellularized leaflets repopulated with aortic valve interstitial cells: the VESALIO Project (Vitalitate Exornatum Succedaneum Aorticum Labore Ingenioso Obtenibitur). Ann Thorac Surg 2003;75:1274-1282.[Abstract/Free Full Text]
  2. Vincentelli A, Wautot F, Juthier F, Fouquet O, Corseaux D, Marechaux S, et al. In vivo autologous recellularization of a tissue-engineered heart valve: are bone marrow mesenchymal stem cells the best candidates?. J Thorac Cardiovasc Surg 2007;134:424-432.[Abstract/Free Full Text]
  3. Juthier F, Vincentelli A, Gaudric J, Corseaux D, Fouquet O, Calet C, et al. Decellularized heart valve as a scaffold for in vivo recellularization: deleterious effects of granulocyte colony-stimulating factor. J Thorac Cardiovasc Surg 2006;131:843-852.[Abstract/Free Full Text]
  4. Dohmen PM, da Costa F, Yoshi S, Lopes SV, da Souza FP, Vilani R, et al. Histological evaluation of tissue-engineered heart valves implanted in the juvenile sheep model: is there a need for in-vitro seeding?. J Heart Valve Dis 2006;15:823-829.[Medline]




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