Abstract
Heart valve diseases are usually treated by surgical intervention addressed for the replacement of the damaged valve with a biosynthetic or mechanical prosthesis. Although this approach guarantees a good quality of life for patients, it is not free from drawbacks (structural deterioration, nonstructural dysfunction, and reintervention). To overcome these limitations, the heart valve tissue engineering (HVTE) is developing new strategies to synthesize novel types of valve substitutes, by identifying efficient sources of both ideal scaffolds and cells. In particular, a natural matrix, able to interact with cellular components, appears to be a suitable solution. On the other hand, the well-known Wharton's jelly mesenchymal stem cells (WJ-MSCs) plasticity, regenerative abilities, and their immunomodulatory capacities make them highly promising for HVTE applications. In the present study, we investigated the possibility to use porcine valve matrix to regenerate in vitro the valve endothelium by WJ-MSCs differentiated along the endothelial lineage, paralleled with human umbilical vein endothelial cells (HUVECs), used as positive control. Here, we were able to successfully decellularize porcine heart valves, which were then recellularized with both differentiated-WJ-MSCs and HUVECs. Data demonstrated that both cell types were able to reconstitute a cellular monolayer. Cells were able to positively interact with the natural matrix and demonstrated the surface expression of typical endothelial markers. Altogether, these data suggest that the interaction between a biological scaffold and WJ-MSCs allows the regeneration of a morphologically well-structured endothelium, opening new perspectives in the field of HVTE.
Highlights
In the past two decades, cardiac valve diseases have undergone deep changes, concerning the epidemiological, diagnostic, and therapeutic point of views
Wharton’s jelly, the mucoid connective tissue composing the umbilical cord (UC), is emerging as an interesting source of mesenchymal stem cells (MSCs) (WJ-MSCs), since Wharton’s jelly mesenchymal stem cells (WJ-MSCs) are available, stable for several passages, and able to differentiate along the endothelial lineage.[15,16]. Moving from these evidences, the present study evaluated the ability of WJ-MSCs and human umbilical vein endothelial cells (HUVECs)[4] to reconstitute an efficient valve endothelium by using a decellularized porcine scaffold as a substratum for the neoendothelium growth
The absence of cell nuclei (Fig. 1A-d) underlined the autofluorescence of the decellularized matrix; such a green autofluorescence disappeared when porcine valve are covered by the native endothelium (Fig. 1Ab)
Summary
In the past two decades, cardiac valve diseases have undergone deep changes, concerning the epidemiological, diagnostic, and therapeutic point of views. Heart valve diseases associated to degenerative processes have become the most frequent pathologies.[1] Regarding the diagnosis, remarkable progresses in imaging techniques allowed a more focused selection of candidates and an optimal timing for surgical correction. In such a context, echocardiography is considered the gold standard for diagnosis of heart valve diseases.[2,3] The best therapeutic approach for their treatment is based on surgical valve replacement by mechanical or biological prosthesis implantation.[1]
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