Serum-free differentiation of functional human coronary-like vascular smooth muscle cells from embryonic stem cells

El-Mounayri, Omar; Mihic, Anton; Shikatani, Eric A.; Gagliardi, Mark; Steinbach, Sarah K.; Dubois, Nicole; DaCosta, Ralph S.; Li, Ren‐Ke; Keller, Gordon; Husain, Mansoor

doi:10.1093/cvr/cvs357

Cited by 32 publications

(19 citation statements)

References 40 publications

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“…For example, deriving coronary artery SMCs would facilitate further studies on the differences between atherosclerosis in this critical vascular bed compared to other vascular territories. Recently, El-Mounayri and colleagues [99] described a serum-free method of generating SMCs using directed differentiation of embryoid bodies towards a cardiac fate. The derived SMCs were deemed ‘coronary’ by the similarity of their Ca 2+ and contractile responses to coronary SMC controls.…”

Section: Generation Of Human Embryonic Stem Cell-derived Smooth Musclmentioning

confidence: 99%

Embryonic origins of human vascular smooth muscle cells: implications for in vitro modeling and clinical application

Sinha

Iyer

Granata

2014

Cell. Mol. Life Sci.

122

103

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Vascular smooth muscle cells (SMCs) arise from multiple origins during development, raising the possibility that differences in embryological origins between SMCs could contribute to site-specific localization of vascular diseases. In this review, we first examine the developmental pathways and embryological origins of vascular SMCs and then discuss in vitro strategies for deriving SMCs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We then review in detail the potential for vascular disease modeling using iPSC-derived SMCs and consider the pathological implications of heterogeneous embryonic origins. Finally, we touch upon the role of human ESC-derived SMCs in therapeutic revascularization and the challenges remaining before regenerative medicine using ESC- or iPSC-derived cells comes of age.

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Section: Generation Of Human Embryonic Stem Cell-derived Smooth Musclmentioning

confidence: 99%

Embryonic origins of human vascular smooth muscle cells: implications for in vitro modeling and clinical application

Sinha

Iyer

Granata

2014

Cell. Mol. Life Sci.

122

103

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“…57 Tissue-specific mesodermal VSMCs have also been generated via the EB method using a serum-free protocol to generate functional and clinically viable coronary arterylike VSMCs. 58 In fact, this study revealed that only at day 28 of EB formation did fully differentiated VSMCs appear and that these cells required the combined signaling of both VEGF and bFGF for maintenance of the phenotype ( Figure 1B).…”

Section: Embryoid Body Methodsmentioning

confidence: 80%

Differentiation and Application of Induced Pluripotent Stem Cell–Derived Vascular Smooth Muscle Cells

Maguire

Xiao

2017

ATVB

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Abstract-Vascular smooth muscle cells (VSMCs) play a role in the development of vascular disease, for example, neointimal formation, arterial aneurysm, and Marfan syndrome caused by genetic mutations in VSMCs, but little is known about the mechanisms of the disease process. Advances in induced pluripotent stem cell technology have now made it possible to derive VSMCs from several different somatic cells using a selection of protocols. As such, researchers have set out to delineate key signaling processes involved in triggering VSMC gene expression to grasp the extent of gene regulatory networks involved in phenotype commitment. This technology has also paved the way for investigations into diseases affecting VSMC behavior and function, which may be treatable once an identifiable culprit molecule or gene has been repaired. Moreover, induced pluripotent stem cell-derived VSMCs are also being considered for their use in tissue-engineered blood vessels as they may prove more beneficial than using autologous vessels. Finally, while several issues remains to be clarified before induced pluripotent stem cell-derived VSMCs can become used in regenerative medicine, they do offer both clinicians and researchers hope for both treating and understanding vascular disease. In this review, we aim to update the recent progress on VSMC generation from stem cells and the underlying molecular mechanisms of VSMC differentiation. We will also explore how the use of induced pluripotent stem cell-derived VSMCs has changed the game for regenerative medicine by offering new therapeutic avenues to clinicians, as well as providing researchers with a new platform for modeling of vascular disease. Visual Overview-An online visual overview is available for this article.

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“…While in vitro models have only generated PC from the LPM, VSMC have been generated from the NC, LPM, PM, and CM, and display a diversity of properties that match their in vivo counterparts [19,83].…”

Section: Considering Origin Heterogeneity In Vitromentioning

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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Serum-free differentiation of functional human coronary-like vascular smooth muscle cells from embryonic stem cells

Abstract: The ability to generate hESC-derived functional human coronary-like VSMCs in serum-free conditions has implications for disease modelling, drug screening, and regenerative therapies.

Cited by 32 publications

References 40 publications

Embryonic origins of human vascular smooth muscle cells: implications for in vitro modeling and clinical application

Embryonic origins of human vascular smooth muscle cells: implications for in vitro modeling and clinical application

Differentiation and Application of Induced Pluripotent Stem Cell–Derived Vascular Smooth Muscle Cells

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

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