Small diameter vascular graft engineered using human embryonic stem cell-derived mesenchymal cells

Abstract

Despite the progress made thus far in the generation of small-diameter vascular grafts, cell sourcing still remains a problem. Human embryonic stem cells (hESCs) present an exciting new cell source for the regeneration applications due to their high proliferative and differentiation capabilities. In this study, the feasibility of creating small-diameter vascular constructs using smooth muscle cells (SMCs) differentiated from hESCderived mesenchymal cells was evaluated. In vitro experiments confirmed the ability of these cells to differentiate into smooth muscle actin-and calponin-expressing SMCs in the presence of known inducers, such as transforming growth factor beta. Human vessel walls were constructed by culturing these cells in a bioreactor system under pulsatile conditions for 8 weeks. Histological analysis showed that vessel grafts had similarities to their native counterparts in terms of cellularity and SMC marker expression. However, markers of cartilage and bone tissue were also detected, thus raising questions about stable lineage commitment during differentiation and calling for more stringent analysis of differentiating cell populations.

Regenerative and durable small-diameter graft as an arterial conduit

“…small-diameter vascular graft | infrarenal abdominal aorta mouse model | electrospinning | hydrogel | endothelial colony-forming cells T here is a significant need for small-diameter vascular grafts (sdVGs; <6 mm in diameter) for the treatment of various arterial complications, such as coronary artery disease (CAD) and pediatric congenital cardiovascular defects (CCDs). CAD is the leading cause of death or impaired quality of life, resulting in more than half a million coronary artery bypass surgeries per year (1)(2)(3)(4). Meanwhile, pediatric CCDs are present in 1% of live births (5), with most cases requiring repeated surgical reconstruction to maximize long-term survival (5)(6)(7).…”

Proteomic Analysis of the Pericyte Derived Extracellular Matrix

“…Recent advancements in the development of biomimetic materials and scaffolds have demonstrated that the ability to preserve or replicate the biochemical and mechanical properties of the ECM is key to the retention of appropriate, and in some cases, pathological cell function. 10,28,32,40 Cell derived ECM proteins from whole tissue or that derived from cultured cells are frequently used for experimental investigations of cell response to the microenvironment, and tissue engineering of whole organs, large vessels (arteries and veins) and small blood vessels (arterioles, venules, and capillary structures). In particular, fibroblast and smooth muscle cell (SMC) derived ECM are commonly used in experimental studies and commercial tissue engineered structures, including tissue engineered vascular grafts (TEVG), each requiring an appropriate EC adhesive and proliferative response.…”

Stem cell-derived vasculature: A potent and multidimensional technology for basic research, disease modeling, and tissue engineering

“…As the field began attempting smaller diameter grafts, neointimal hyperplasia and thrombus formation bedeviled the transplants and many grafts failed either due to insufficient transport properties or biomechanical failure. As these problems surfaced, so did novel biomaterials and combinations with various stem cell components attempting to solve it [74,76]. Investigators have likewise been creating more advanced tissue-engineered vascular grafts utilizing novel bioreactor/culture systems and stem cell sources, including iPSCs [77,78].…”