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Review
. 2021 Oct;17(5):1741-1753.
doi: 10.1007/s12015-021-10149-3. Epub 2021 Mar 18.

Induced Pluripotent Stem Cells (iPSCs) in Vascular Research: from Two- to Three-Dimensional Organoids

Affiliations
Review

Induced Pluripotent Stem Cells (iPSCs) in Vascular Research: from Two- to Three-Dimensional Organoids

Anja Trillhaase et al. Stem Cell Rev Rep. 2021 Oct.

Abstract

Stem cell technology has been around for almost 30 years and in that time has grown into an enormous field. The stem cell technique progressed from the first successful isolation of mammalian embryonic stem cells (ESCs) in the 1990s, to the production of human induced-pluripotent stem cells (iPSCs) in the early 2000s, to finally culminate in the differentiation of pluripotent cells into highly specialized cell types, such as neurons, endothelial cells (ECs), cardiomyocytes, fibroblasts, and lung and intestinal cells, in the last decades. In recent times, we have attained a new height in stem cell research whereby we can produce 3D organoids derived from stem cells that more accurately mimic the in vivo environment. This review summarizes the development of stem cell research in the context of vascular research ranging from differentiation techniques of ECs and smooth muscle cells (SMCs) to the generation of vascularized 3D organoids. Furthermore, the different techniques are critically reviewed, and future applications of current 3D models are reported.

Keywords: Differentiation; Endothelial cells; Induced pluripotent stem cells; Organoids; Smooth muscle cells; Vasculature.

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Conflict of interest statement

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Figures

Fig. 1
Fig. 1
Achievements and Milestones in iPSC research. Timeline showing the achievements of iPSC technology since 1998, divided into general milestones and time-points when smooth muscle and endothelial cell derivatives were successful generated
Fig. 2
Fig. 2
Shown is the human vascular system, with a magnified transverse section through the aorta. Further magnified is a cross-section of the vessel wall, divided into the different layers with the corresponding components
Fig. 3
Fig. 3
Embryological differentiation pathways of VSMCs and ECs
Fig. 4
Fig. 4
VSMC phenotypic switch between contractile and synthetic phenotype. Various factors contribute to VSMC phenotypic switch, including cell interactions between ECs and SMCs, mechanical forces, ECM composition, oxygen (O2), neuronal effects, injury, and inflammation

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