Early Insight into In Vivo Recellularization of Cell-Free Allogenic Heart Valves

Background: Recellularization is the prerequisite for regeneration and good long-term function of cell-free homografts. Unlike the vast amount of animal data available on the recellularization of allogenic decellularized heart valves (DHVs), there have only been sporadic histological reports on such grafts in humans.

Methods: Immunohistological assessment of all human specimens obtained during reoperation between January 2005 and April 2017after implantation of fresh, noncryopreserved, and nonseeded DHVs. Two experienced cardiac pathologists independently evaluated DHV structure as well as the amount and type of recellularization in seven categories (scores 0–6) in comparison to published data. An optimal result of 42 points was classified as 100%.

Results: A total of 364 DHVs, 236 pulmonary (DPH), and 128 aortic (DAH) were implanted; freedom from explantation was 96.1% (DAH) and 98.7% (DPH). Eleven specimens (seven explants and four biopsies) were analyzed. Reoperations were due to (suspected) endocarditis in 5/11, stenosis either at subvalvular/valvular/supravalvular level in 3/11, planned staged reoperation in 2/11, and 1 heart transplant.

Good reader agreement was reflected by an interagreement weighted Kappa of 0.783 (0.707–0.859, 95% CI). The relative histological score in nonendocarditis cases was 76% (±4.3, max. 81%). The anticipated cell groups (endothelial, mesenchymal, and smooth muscle) were observed as well as good preservation of matrix structure and absent immune competent cells. Intracellular procollagen type 1 production was found in recipient mesenchymal cells within the transplanted grafts. In endocarditis cases, the histological score was significantly lower with 48% (±7.3, min. 41%, p = 0.0004) due to leucocyte infiltration and matrix degradation. An interesting observation was that grafts obtained during the first 12 months after implantation were not evenly repopulated with less recellularization in the inner parts; no difference was found between DAH and DPH with respect to the extent of recellularization.

Conclusion: Significant in vivo recellularization with noninflammatory cells was observed in this study, which is limited by the heterogeneity of available samples and potential bias due to a negative selection.

The finding of relatively slow recellularization may have implications for size selection, as autologous regeneration of the allogenic matrix may not be sufficient in the first 9 to 12 months, thereby necessitating oversizing in growing patients.