Vascular smooth muscle cell differentiation from human stem/progenitor cells

Steinbach, Sarah K.; Husain, Mansoor

doi:10.1016/j.ymeth.2015.12.004

Cited by 21 publications

(17 citation statements)

References 67 publications

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“…Human iPSCs are an attractive source for these vascular cell types due to the ability to easily expand and culture iPSCs prior to differentiation to the desired cell type as well as the ease of acquisition from human subjects. In terms of SMCs, this is particularly important due to the slow culture growth and quick senescence of primary cell sources 18 . iPSCs also provide the ability to create patient specific disease models due to their capability to maintain a disease phenotype post-differentiation 12 .…”

Section: Introductionmentioning

confidence: 99%

A Tissue Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome Using Human iPSC-derived Smooth Muscle Cells

Atchison

Zhang

Cao

et al. 2017

Sci Rep

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Hutchison-Gilford Progeria Syndrome (HGPS) is a rare, accelerated aging disorder caused by nuclear accumulation of progerin, an altered form of the Lamin A gene. The primary cause of death is cardiovascular disease at about 14 years. Loss and dysfunction of smooth muscle cells (SMCs) in the vasculature may cause defects associated with HGPS. Due to limitations of 2D cell culture and mouse models, there is a need to develop improved models to discover novel therapeutics. To address this need, we produced a functional three-dimensional model of HGPS that replicates an arteriole-scale tissue engineered blood vessel (TEBV) using induced pluripotent stem cell (iPSC)-derived SMCs from an HGPS patient. To isolate the effect of the HGPS iSMCs, the endothelial layer consisted of human cord blood-derived endothelial progenitor cells (hCB-EPCs) from a separate, healthy donor. TEBVs fabricated from HGPS iSMCs and hCB-EPCs show reduced vasoactivity, increased medial wall thickness, increased calcification and apoptosis relative to TEBVs fabricated from normal iSMCs or primary MSCs. Additionally, treatment of HGPS TEBVs with the proposed therapeutic Everolimus, increases HGPS TEBV vasoactivity and increases iSMC differentiation in the TEBVs. These results show the ability of this iPSC-derived TEBV to reproduce key features of HGPS and respond to drugs.

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Section: Introductionmentioning

confidence: 99%

A Tissue Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome Using Human iPSC-derived Smooth Muscle Cells

Atchison

Zhang

Cao

et al. 2017

Sci Rep

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“…Other sources of stem cells with the potential to be differentiated into VSMCs are human pluripotent stem cells, obtained from embryonic tissues [47,48] and induced pluripotent stem cells (iPSCs) [49][50][51]. However, the use of these cells, although promising, is associated with ethical and legal issues in human embryonic stem cells and with a risk of potential tumorigenicity of iPSCs.…”

Section: Use Of Stem Cells As a Source Of Vsmcs For Blood Vessel Tissmentioning

confidence: 99%

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

Bačáková¹,

Trávníčková²,

Filová³

et al. 2018

Muscle Cell and Tissue - Current Status of Research Field

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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.

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“…16 For instance, a combination of BMP4 (bone morphogenic protein 4), activin and fibroblast growth factor 2 (FGF2) is required to generate mesodermal VSMCs. 17 Indeed Steinbach et al 18 2016 describe stepwise administration of key members of the transforming growth factor-β (TGF-β) superfamily to generate lateral plate-derived VSMCs from hPSCs. And more specifically proepicardial VSMCs are generated from hPSCs by precisely controlled administration of BMP2, 19 which crucially require activation of the BMP and Wnt signaling pathways to induce epithelial to mesenchymal transition for further specification toward the VSMC phenotype.…”

Section: Vsmc Origin and Differentiationmentioning

confidence: 99%

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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Vascular smooth muscle cell differentiation from human stem/progenitor cells

Cited by 21 publications

References 67 publications

A Tissue Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome Using Human iPSC-derived Smooth Muscle Cells

A Tissue Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome Using Human iPSC-derived Smooth Muscle Cells

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

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

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