Endothelial Cells Direct Mesenchymal Stem Cells Toward a Smooth Muscle Cell Fate

Lin, Cho-Hao; Lilly, Brenda

doi:10.1089/scd.2014.0163

Cited by 40 publications

(29 citation statements)

References 27 publications

(36 reference statements)

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“…26, 28 To examine the extent of this modulation by endothelial cells, we measured the expression of the microRNA gene cluster miR-143/145 , which has been linked to governing smooth muscle differentiation. 14, 16, 18 Coculture of human umbilical vein endothelial cells (HUVECs) with human aortic smooth muscle cells (HAoSMCs) caused an increase in precursor microRNA pri-miR-143/145 transcript as well as the individual mature microRNAs (Figure 1A–C).…”

Section: Resultsmentioning

confidence: 99%

MicroRNA miR145 Regulates TGFBR2 Expression and Matrix Synthesis in Vascular Smooth Muscle Cells

Zhao

Koenig

Trask

et al. 2015

Circulation Research

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Rationale MicroRNA miR145 has been implicated in vascular smooth muscle cell differentiation, but its mechanisms of action and downstream targets have not been fully defined. Objective Here, we sought to explore and define the mechanisms of miR145 function in smooth muscle cells. Methods and Results Using a combination of cell culture assays and in vivo mouse models to modulate miR145, we characterized its downstream actions on smooth muscle phenotypes. Our results show that the miR-143/145 gene cluster is induced in smooth muscle cells by coculture with endothelial cells. Endothelial cell-induced expression of miR-143/145 is augmented by Notch signaling and accordingly expression is reduced in Notch receptor-deficient cells. Screens to identify miR145-regulated genes revealed that the TGFβ pathway has a significantly high number of putative target genes, and we show that TGFβ receptor II (TGFBR2) is a direct target of miR145. Extracellular matrix (ECM) genes that are regulated by TGFBR2 were attenuated by miR145 overexpression, and miR145 mutant mice exhibit an increase in ECM synthesis. Furthermore, activation of TGFβ signaling via angiotensin II infusion revealed a pronounced fibrotic response in the absence of miR145. Conclusions These data demonstrate a specific role for miR145 in the regulation of matrix gene expression in smooth muscle cells, and suggest that miR145 acts to suppress TGFβ-dependent ECM accumulation and fibrosis, while promoting TGFβ-induced smooth muscle cell differentiation. Our findings offer evidence to explain how TGFβ signaling exhibits distinct downstream actions via its regulation by a specific microRNA.

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Section: Resultsmentioning

confidence: 99%

MicroRNA miR145 Regulates TGFBR2 Expression and Matrix Synthesis in Vascular Smooth Muscle Cells

Zhao

Koenig

Trask

et al. 2015

Circulation Research

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“…Moreover, ECs can drive MSCs toward a smooth muscle lineage. A recent report from Lin and Lilly [2014] showed that in coculture ECs induced SMC differentiation in MSCs. ECs can promote a contractile phenotype, reduce proliferation, and enhance collagen synthesis and secretion.…”

Section: Application In Tebvsmentioning

confidence: 99%

“…Source MSCs are multipotent stromal cells with the ability to self-renew and differentiate into a variety of cell types, including osteoblasts, chondrocytes, ECs, SMCs and adipocytes [Beyer Nardi and da Silva Meirelles, 2006;Cui et al, 2012;Lin and Lue, 2013;Lin and Lilly, 2014]. They have the potential be used allogenically to improve the outcomes of damaged tissue repair due to their anti-inflammatory, antifibrotic, antimicrobial, and regenerative properties, and lack of major histocompatibility complex (MHC) II [Park et al, 2007;Sutton and Bonfield, 2014].…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Scaffolds and Cell-Based Tissue Engineering for Blood Vessel Therapy

Hsia

Yao

Chen

et al. 2016

Cells Tissues Organs

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The increasing morbidity of cardiovascular diseases in modern society has made it crucial to develop a small-caliber blood vessel. In the absence of appropriate autologous vascular grafts, an alternative prosthesis must be constructed for cardiovascular disease patients. The aim of this article is to describe the advances in making cell-seeded cardiovascular prostheses. It also discusses the combinations of types of scaffolds and cells, especially autologous stem cells, which are suitable for application in tissue-engineered vessels with the favorable properties of mechanical strength, antithrombogenicity, biocompliance, anti-inflammation, fatigue resistance and long-term durability. This article highlights the advancements in cellular tissue-engineered vessels in recent years.

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“…In vitro, activation of the Notch pathway and subsequent differentiation of SMC precursors can be achieved with exogenous introduction or overexpression of Jag1 or NICD [126,129]. VSMC differentiation studies have also activated the Notch pathway with coculture of EC or other cells that express Notch ligands [127,132].…”

Section: Cell-cell Contact Signalingmentioning

confidence: 99%

Development of Mural Cells: From In Vivo Understanding to In Vitro Recapitulation

Shen¹,

McCloskey

2017

Stem Cells and Development

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Mural cells are indispensable for the development and maintenance of healthy mature vasculature, valuable for vascular therapies and as developmental models. However, their functional plasticity, developmental diversity, and multitude of differentiation pathways complicate in vitro generation. Fortunately, there is a vast pool of untapped knowledge from in vivo studies that can guide in vitro engineering. This review highlights the in vivo genesis of mural cells from progenitor populations to recruitment pathways to maturation and identity with an emphasis on how this knowledge is applicable to in vitro models of stem cell differentiation.

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Endothelial Cells Direct Mesenchymal Stem Cells Toward a Smooth Muscle Cell Fate

Cited by 40 publications

References 27 publications

MicroRNA miR145 Regulates TGFBR2 Expression and Matrix Synthesis in Vascular Smooth Muscle Cells

MicroRNA miR145 Regulates TGFBR2 Expression and Matrix Synthesis in Vascular Smooth Muscle Cells

Scaffolds and Cell-Based Tissue Engineering for Blood Vessel Therapy

Development of Mural Cells: From In Vivo Understanding to In Vitro Recapitulation

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