Generation and Characterization of Human Mesenchymal Stem Cell-Derived Smooth Muscle Cells

Abstract

Cardiovascular diseases are the leading cause of death worldwide. A completely autologous treatment can be achieved by using elastogenic mesenchymal stem cell (MSC)-derived smooth muscle cells (SMC) at the affected tissue site of vascular diseases such as abdominal aortic aneurysms (AAA). Thus, our work focused on evaluating the efficacy of (a) the combination of various growth factors, (b) different time periods and (c) different MSC lines to determine the treatment combination that generated SMCs that exhibited the greatest elastogenicity among the tested groups using Western blotting and flow cytometry. Additionally, total RNA sequencing was used to confirm that post-differentiation cells were upregulating SMC-specific gene markers. Results indicated that MSCs cultured for four days in PDGF + TGFβ1 (PT)-infused differentiation medium showed significant increases in SMC markers and decreases in MSC markers compared to MSCs cultured without differentiation factors. RNA Seq analysis confirmed the presence of vascular smooth muscle formation in MSCs differentiated in PT medium over a seven-day period. Overall, our results indicated that origin, growth factor treatment and culture period played a major role in influencing MSC differentiation to SMCs.

Designer umbilical cord-stem cells induce alveolar wall regeneration in pulmonary disease models

“…hUC-MSCs cultured on collagen I and laminin 411 (Gel-L411 dUC-MSCs) showed the highest expression levels of vascular endothelial markers and myofibroblast progenitor cell markers in vitro and retained their anti-inflammatory effects without undergoing genetic modifications. During the regeneration of the destroyed basement membrane and ECM, MSCs differentiate into myofibroblasts ( 32 ) and pulmonary capillary endothelial cells ( 33 ), and their interaction contributes to angiogenesis and alveolus formation ( Figure 4C ). dUC-MSCs exhibited a higher adhesion capacity than normally cultured hUC-MSCs.…”

Mesenchymal Stromal Cell-Derived Extracellular Vesicles for Vasculopathies and Angiogenesis: Therapeutic Applications and Optimization

“…Resident/native CD34+ stromal cells/progenitor cells lose the expression of CD34 and are a source of alpha+ SMA myofibroblasts during different stages of repair [5]. MSCs can also differentiate into endothelial cells (ECs) or vascular smooth muscle cells (SMCs) under conditioned circumstances [6,7]. Various features, such as scalability and Biomolecules 2023, 13, 1109 2 of 20 immune privileges, make MSCs ideal candidates for disease therapy.…”

Differentiation and quality control of smooth muscle cells from human pluripotent stem cells via the neural crest lineage

“…Consequently, studying disease-related SMCs in vitro requires differentiation methods that derive lineage-specific cells. A further caveat is that stem cell differentiations can be variable between laboratories or even for individual researchers (Volpato et al, 2018a) and that care must be taken in deriving SMCs in vitro (Sivaraman et al, 2021).…”