Engineering tissue‐specific blood vessels

Herron, Lauren; Hansen, C.; Abaci, Hasan Erbil

doi:10.1002/btm2.10139

Cited by 23 publications

(14 citation statements)

References 108 publications

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“…In vitro formation of luminal vasculature facilitates the circulation of culture medium (i.e., nutrients and oxygen) inside organoids and may also recapitulate physiological interactions between blood vessels and parenchymal cells under pathological conditions. Numerous attempts have been made to recapitulate the human vascular microenvironment in 3D organ models in vitro by using microfluidic devices, bioprinting, and biomaterials [ 65 ]. To the best of our knowledge, however, in vitro generation of perfusable vasculature in self-organized liver organoids has not been reported.…”

Section: Resultsmentioning

confidence: 99%

Generation of multilineage liver organoids with luminal vasculature and bile ducts from human pluripotent stem cells via modulation of Notch signaling

Kim

Yoo

et al. 2023

Stem Cell Res Ther

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Background The generation of liver organoids recapitulating parenchymal and non-parenchymal cell interplay is essential for the precise in vitro modeling of liver diseases. Although different types of multilineage liver organoids (mLOs) have been generated from human pluripotent stem cells (hPSCs), the assembly and concurrent differentiation of multiple cell types in individual mLOs remain a major challenge. Particularly, most studies focused on the vascularization of mLOs in host tissue after transplantation in vivo. However, relatively little information is available on the in vitro formation of luminal vasculature in mLOs themselves. Methods The mLOs with luminal blood vessels and bile ducts were generated by assembling hepatic endoderm, hepatic stellate cell-like cells (HscLCs), and endothelial cells derived entirely from hPSCs using 96-well ultra-low attachment plates. We analyzed the effect of HscLC incorporation and Notch signaling modulation on the formation of both bile ducts and vasculature in mLOs using immunofluorescence staining, qRT-PCR, ELISA, and live-perfusion imaging. The potential use of the mLOs in fibrosis modeling was evaluated by histological and gene expression analyses after treatment with pro-fibrotic cytokines. Results We found that hPSC-derived HscLCs are crucial for generating functional microvasculature in mLOs. HscLC incorporation and subsequent vascularization substantially reduced apoptotic cell death and promoted the survival and growth of mLOs with microvessels. In particular, precise modulation of Notch signaling during a specific time window in organoid differentiation was critical for generating both bile ducts and vasculature. Live-cell imaging, a series of confocal scans, and electron microscopy demonstrated that blood vessels were well distributed inside mLOs and had perfusable lumens in vitro. In addition, exposure of mLOs to pro-fibrotic cytokines induced early fibrosis-associated events, including upregulation of genes associated with fibrotic induction and endothelial cell activation (i.e., collagen I, α-SMA, and ICAM) together with destruction of tissue architecture and organoid shrinkage. Conclusion Our results demonstrate that mLOs can reproduce parenchymal and non-parenchymal cell interactions and suggest that their application can advance the precise modeling of liver diseases in vitro.

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Section: Resultsmentioning

confidence: 99%

Generation of multilineage liver organoids with luminal vasculature and bile ducts from human pluripotent stem cells via modulation of Notch signaling

Kim

Yoo

et al. 2023

Stem Cell Res Ther

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“…Microvascular ECs collected from adult organs display differences in both structural attributes and molecular expression profiles (39)(40)(41). In one study, ECs of four major human organs-the heart, lung, liver, and kidneys-were isolated from fetal tissues.…”

Section: Components Of Self-assembled Microvasculature Endothelial Cellsmentioning

confidence: 99%

Engineering Vascularized Organoid-on-a-Chip Models

Shirure

Hughes

George

2021

Annu. Rev. Biomed. Eng.

118

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Recreating human organ–level function in vitro is a rapidly evolving field that integrates tissue engineering, stem cell biology, and microfluidic technology to produce 3D organoids. A critical component of all organs is the vasculature. Herein, we discuss general strategies to create vascularized organoids, including common source materials, and survey previous work using vascularized organoids to recreate specific organ functions and simulate tumor progression. Vascularization is not only an essential component of individual organ function but also responsible for coupling the fate of all organs and their functions. While some success in coupling two or more organs together on a single platform has been demonstrated, we argue that the future of vascularized organoid technology lies in creating organoid systems complete with tissue-specific microvasculature and in coupling multiple organs through a dynamic vascular network to create systems that can respond to changing physiological conditions. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 23 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…12 A useful prioritization of MPS applications can be found in Table 1 of the review by Watson, Hunziker, and Wikswo, 2017. 10 Currently, there are MPS of nearly every major human organ 20 including liver, 16,41 vasculature, 42,43 blood-brain barrier (BBB), [44][45][46] skeletal [47][48][49] and cardiac muscle, [50][51][52][53][54][55][56][57] kidney, [58][59][60][61] female reproductive tissues (uterus, cervix, fallopian tubes), 62 testes, 63 brain, 37,64 skin, [65][66][67] gut, 40 bone, 68 and eye. 69,70 Specific MPS organ systems have also been linked to form multi-organ systems to more accurately depict systemic responses to a variety of drugs and therapeutics.…”

Section: Impact Statementmentioning

confidence: 99%

Microphysiological systems: What it takes for community adoption

Hargrove-Grimes

Low

Tagle

2021

Exp Biol Med (Maywood)

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Microphysiological systems (MPS) are promising in vitro tools which could substantially improve the drug development process, particularly for underserved patient populations such as those with rare diseases, neural disorders, and diseases impacting pediatric populations. Currently, one of the major goals of the National Institutes of Health MPS program, led by the National Center for Advancing Translational Sciences (NCATS), is to demonstrate the utility of this emerging technology and help support the path to community adoption. However, community adoption of MPS technology has been hindered by a variety of factors including biological and technological challenges in device creation, issues with validation and standardization of MPS technology, and potential complications related to commercialization. In this brief Minireview, we offer an NCATS perspective on what current barriers exist to MPS adoption and provide an outlook on the future path to adoption of these in vitro tools.

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Engineering tissue‐specific blood vessels

Cited by 23 publications

References 108 publications

Generation of multilineage liver organoids with luminal vasculature and bile ducts from human pluripotent stem cells via modulation of Notch signaling

Generation of multilineage liver organoids with luminal vasculature and bile ducts from human pluripotent stem cells via modulation of Notch signaling

Engineering Vascularized Organoid-on-a-Chip Models

Microphysiological systems: What it takes for community adoption

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