Vascular Smooth Muscle Cells (VSMCs) in Blood Vessel Tissue Engineering: The Use of Differentiated Cells or Stem Cells as VSMC Precursors

Abstract

Vascular smooth muscle cells (VSMCs) play important roles in the physiology and pathophysiology of the blood vessels. In a healthy adult organism, VSMCs are quiescent, but after a blood vessel injury, they undergo phenotypic modulation from the contractile phenotype to the synthetic phenotype, characterized by high activity in migration, proliferation and proteosynthesis. This behavior of VSMCs can lead to stenosis or obliteration of the vascular lumen. For this reason, VSMCs have tended to be avoided in the construction of blood vessel replacements. However, VSMCs are a physiological and the most numerous component of blood vessels, so their presence in novel advanced vascular replacements is indispensable. Either differentiated VSMCs or stem cells as precursors of VSMCs can be used in the reconstruction of the tunica media in these replacements. VSMCs can be obtained from blood vessels (usually from subcutaneous veins) taken surgically from the patients and can be expanded in vitro. During in vitro cultivation, VSMCs lose their differentiation markers, at least partly. These cells should therefore be re-differentiated by seeding them on appropriate scaffolds by composing cell culture media and by mechanical stimulation in dynamic bioreactors. Similar approaches can also be applied for differentiating stem cells, particularly adipose tissue-derived stem cells, toward VSMCs for the purposes of vascular tissue engineering.

Bioreactor Processed Stromal Cell Seeding and Cultivation on Decellularized Pericardium Patches for Cardiovascular Use

“…This was proven by the expression of an SMC marker calponin. Greater cell population density and greater upregulation of early differentiation markers α-actin and calponin were achieved in a pressure-stimulated culture than in static conditions [18,32]. In this context, two mechanosensitive signaling pathways associated with SMC differentiation have been described: the RhoA-associated pathway, and the FAK kinase-associated pathway.…”

Coupling Osteogenesis and Vasculogenesis in Engineered Orthopedic Tissues

“…However, harvesting of mature SMCs from the walls of large vessels presents a clinical challenge, 79 and fibroblasts may not produce vessels of the same quality as other support cell types. 77 The use of MSCs is therefore of particular interest in tissue engineering, since these cells are abundantly available, secrete proangiogenic factors, 11,80,81 and have the ability to differentiate toward an SMC lineage.…”

Low concentrations of TNF‐α in vitro transform the phenotype of vascular smooth muscle cells and enhance their survival in a three‐dimensional culture system

“…They are abundant in the mid-membrane of biological vascular tissues and are responsible for producing ECM while maintaining vascular mechanical properties. 8,11,12 VSMCs exhibit great plasticity and are not terminally differentiated cells. 13 It has been demonstrated that VSMCs can change from a stable contractile phenotype to a proliferative synthetic phenotype under various conditions.…”

“…The two phenotypes of VSMCs exhibit different characteristics, with synthetic VSMCs found to have higher proliferative activity and migration ability, as well as the ability to promote the deposition of ECM. 11,12,14 The three-dimensional culture environment has a complex effect on the cellular behavior of seeded cells during the culture process, with a variety of effects having been reported. 15,16 Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine with complex and potentially contradictory impacts on cardiac function and pathology, including beneficial effects.…”