Tissue-engineered blood vessel substitute by reconstruction of endothelium using mesenchymal stem cells induced by platelet growth factors

BackgroundCardiovascular diseases remain leaders as the major causes of mortality in Western society. Restoration of the circulation through construction of bypass surgical treatment is regarded as the gold standard treatment of peripheral vascular diseases, and grafts are necessary for this purpose. The great saphenous vein is often not available and synthetic grafts have their limitations. Therefore, new techniques to produce alternative grafts have been developed and, in this sense, tissue engineering is a promising alternative to provide biocompatible grafts. This study objective was to reconstruct the endothelium layer of decellularized vein scaffolds, using mesenchymal stem cells (MSCs) and growth factors obtained from platelets.MethodsFifteen nonpregnant female adult rabbits were used for all experiments. Adipose tissue and vena cava were obtained and subjected to MSCs isolation and tissue decellularization, respectively. MSCs were subjected to differentiation using endothelial inductor growth factor (EIGF) obtained from human platelet lysates. Immunofluorescence, histological and immunohistochemical analyses were employed for the final characterization of the obtained blood vessel substitute.ResultsThe scaffolds were successfully decellularized with sodium dodecyl sulfate. MSCs actively adhered at the scaffolds, and through stimulation with EIGF were differentiated into functional endothelial cells, secreting significantly higher quantities of von Willebrand factor (0.85 μg/mL; P < .05) than cells cultivated under the same conditions, without EIGF (0.085 μg/mL). Cells with evident morphologic characteristics of endothelium were seen at the lumen of the scaffolds. These cells also stained positive for fascin protein, which is highly expressed by differentiated endothelial cells.ConclusionsTaken together, the use of decellularized bioscaffold and subcutaneous MSCs seems to be a potential approach to obtain bioengineered blood vessels, in the presence of EIGF supplementation.

Clinical RelevanceThe reported outcomes and techniques on this paper may be employed to constitute decellularized heterologous blood vessel banks. These specimens may be seeded with the patients' own mesenchymal stem cells, which can be differentiated into functional endothelial cells that secrete von Willebrand factor. This is done through a novel approach using a concentrate of growth factors obtained from the patient's own platelets, also described in this article. Extra steps would be the seeding of smooth muscle cells and adventitial fibroblasts, which also could be differentiated from the patient's mesenchymal stem cells. Finally, an autologous blood vessel substitute can be obtained for cardiovascular peripheral disease graft treatment. These grafts will not induce tissue rejection, as the donor cells are completely removed and replaced by the patient's cells.