Updated Perspectives on Direct Vascular Cellular Reprogramming and Their Potential Applications in Tissue Engineered Vascular Grafts

Abstract

Cardiovascular disease is a globally prevalent disease with far-reaching medical and socio-economic consequences. Although improvements in treatment pathways and revascularisation therapies have slowed disease progression, contemporary management fails to modulate the underlying atherosclerotic process and sustainably replace damaged arterial tissue. Direct cellular reprogramming is a rapidly evolving and innovative tissue regenerative approach that holds promise to restore functional vasculature and restore blood perfusion. The approach utilises cell plasticity to directly convert somatic cells to another cell fate without a pluripotent stage. In this narrative literature review, we comprehensively analyse and compare direct reprogramming protocols to generate endothelial cells, vascular smooth muscle cells and vascular progenitors. Specifically, we carefully examine the reprogramming factors, their molecular mechanisms, conversion efficacies and therapeutic benefits for each induced vascular cell. Attention is given to the application of these novel approaches with tissue engineered vascular grafts as a therapeutic and disease-modelling platform for cardiovascular diseases. We conclude with a discussion on the ethics of direct reprogramming, its current challenges, and future perspectives.

Autoimmune Haemolytic Anaemia and Anastomosing Haemangioma: “A Possible Relationship”

“…Several studies have reported small colonies of progenitor cells found in various locations in the arterial wall, particularly in the adventitia. These progenitor cells include endothelial, smooth muscle and haematopoietic stem/progenitor cells [19,20]. The nodular image ventral to the abdominal aorta on CT scan 2020 may correspond to these small colonies of progenitor cells, which would be the start of the anastomosing haemangioma.…”

Understanding genomic medicine for thoracic aortic disease through the lens of induced pluripotent stem cells

“…When comparing uniaxial stretch in 2D culture to a 3D construct, there is significantly higher increase in VSMC specific markers ACTA2 and calponin ( 160 ) suggesting that a 3D environment allows for more robust cell-cell and cell-matrix interactions. For this purpose, several 3D models ( 161 ) have been in development over the last several years that incorporate multiple cell types in a bio-degradable matrix. Some key formats include vascular organoids (VOs) ( 138 ), vessel on a chip microfluidic device (VoC) and bioink-based extrusion or bioprinting.…”

Biomechanical Study and Analysis for Cardiovascular/Skeletal Materials and Devices

“…Cardiovascular and orthopedic diseases are two global epidemic diseases with far-reaching medical and socio-economic consequences [ 7 ]. Understanding the mechanical characteristics of arterial walls, blood flow, and valves holds great importance for the diagnosis, management, and treatment of cardiovascular diseases [ 8 , 9 , 10 ].…”