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

Trillhaase, Anja; Maertens, Marlon; Aherrahrou, Zouhair; Erdmann, Jeanette

doi:10.1007/s12015-021-10149-3

Cited by 6 publications

(6 citation statements)

References 60 publications

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“…Experiments have shown that DBD decoction can promote the release of astragalus components, and the process of making freeze-dried powder may cause certain changes in the components of DBD ( Yan et al, 2010 ; Tan et al, 2021 ). Simultaneously, we will further apply vascular organoids coupled with microfluidic mass spectrometry chips to define the potential pharmacological components and deep-level molecular mechanisms of DBD on dilating blood vessels ( Wang et al, 2019 and, 2020 ; Trillhaase et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Anticonstriction Effect of MCA in Rats by Danggui Buxue Decoction

et al. 2021

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Objective: Danggui Buxue decoction (DBD), consisting of Angelicae Sinensis Radix (ASR) and Astragali Radix (AR), is a famous prescription with the function of antivasoconstriction. This study intends to probe its mechanisms on the relaxation of the middle cerebral artery (MCA).Methods: Vascular tension of rat MCA was measured using a DMT620 M system. First, the identical series of concentrations of DBD, ASR, and AR were added into resting KCl and U46619 preconstricted MCA. According to the compatibility ratio, their dilatation effects were further investigated on KCl and U46619 preconstricted vessels. Third, four K+ channel blockers were employed to probe the vasodilator mechanism on KCl-contracted MCA. We finally examined the effects of DBD, ASR, and AR on the vascular tone of U46619-contracted MCA in the presence or absence of Ca2+.Results: Data suggested that DBD, ASR, and AR can relax on KCl and U46619 precontracted MCA with no effects on resting vessels. The vasodilator effect of ASR was greater than those of DBD and AR on KCl-contracted MCA. For U46619-contracted MCA, ASR showed a stronger vasodilator effect than DBD and AR at low concentrations, but DBD was stronger than ASR at high concentrations. Amazingly, the vasodilator effect of DBD was stronger than that of AR at all concentrations on two vasoconstrictors which evoked MCA. The vasodilator effect of ASR was superior to that of DBD at a compatibility ratio on KCl-contracted MCA at low concentrations, while being inferior to DBD at high concentrations. However, DBD exceeded AR in vasodilating MCA at all concentrations. For U46619-constricted MCA, DBD, ASR, and AR had almost identical vasodilation. The dilation of DBD and AR on KCl-contracted MCA was independent of K+ channel blockers. However, ASR may inhibit the K+ channel opening partially through synergistic interactions with Gli and BaCl2. DBD, ASR, and AR may be responsible for inhibiting [Ca2+]out, while ASR and AR can also inhibit [Ca2+]in.Conclusion: DBD can relax MCA with no effects on resting vessels. The mechanism may be related to ASR’s inhibition of KATP and Kir channels. Meanwhile, the inhibition of [Ca2+]out by DBD, ASR, and AR as well as the inhibition of [Ca2+]in by ASR and AR may contribute to dilate MCA.

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Section: Discussionmentioning

confidence: 99%

Anticonstriction Effect of MCA in Rats by Danggui Buxue Decoction

et al. 2021

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“…Attempts to use iPSCs to model vascular cell types began in the late 2000s ( 93 , 94 ) resulting in a mix of several cells including VSMCs and endothelial cells (ECs), in a form of co-culture. Since then, a large number of protocols have been described using highly defined media with small molecules or cytokine cocktails to drive differentiation [several of which are well summarised in these reviews ( 95 – 97 )] that claim to have successfully produced VSMCs or ECs of high purities, organ-specific, developmentally pertinent lineages ( 73 , 76 ) and fine-tuned phenotypic states including the contractile one ( 37 , 98 , 99 ).…”

Section: Disease Modelling Of Tadmentioning

confidence: 99%

Understanding genomic medicine for thoracic aortic disease through the lens of induced pluripotent stem cells

Singh,

Shetty,

Jacob

et al. 2024

Front. Cardiovasc. Med.

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Thoracic aortic disease (TAD) is often silent until a life-threatening complication occurs. However, genetic information can inform both identification and treatment at an early stage. Indeed, a diagnosis is important for personalised surveillance and intervention plans, as well as cascade screening of family members. Currently, only 20% of heritable TAD patients have a causative mutation identified and, consequently, further advances in genetic coverage are required to define the remaining molecular landscape. The rapid expansion of next generation sequencing technologies is providing a huge resource of genetic data, but a critical issue remains in functionally validating these findings. Induced pluripotent stem cells (iPSCs) are patient-derived, reprogrammed cell lines which allow mechanistic insights, complex modelling of genetic disease and a platform to study aortic genetic variants. This review will address the need for iPSCs as a frontline diagnostic tool to evaluate variants identified by genomic discovery studies and explore their evolving role in biological insight through to drug discovery.

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“…In the early stage of development, the embryonic heart is regulated by a variety of signal pathways such as Wnt, BMP, and Notch from surrounding tissues. Wnt signal is not only a key signal pathway involved in the development of cardiac mesoderm, but also an important regulatory pathway for PSC-derived cardiac lineage cells and the construction of cardiac organoids (Trillhaase et al, 2021). Therefore, when constructing cardiac organoids in vitro, it is necessary to add additional exogenous cardiogenic factors to simulate the environment for heart development in vivo (Andersen et al, 2018).…”

Section: Cardiac Organoidsmentioning

confidence: 99%

Merits and challenges of iPSC-derived organoids for clinical applications

Yang

Xin

et al. 2023

Front. Cell Dev. Biol.

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Induced pluripotent stem cells (iPSCs) have entered an unprecedented state of development since they were first generated. They have played a critical role in disease modeling, drug discovery, and cell replacement therapy, and have contributed to the evolution of disciplines such as cell biology, pathophysiology of diseases, and regenerative medicine. Organoids, the stem cell-derived 3D culture systems that mimic the structure and function of organs in vitro, have been widely used in developmental research, disease modeling, and drug screening. Recent advances in combining iPSCs with 3D organoids are facilitating further applications of iPSCs in disease research. Organoids derived from embryonic stem cells, iPSCs, and multi-tissue stem/progenitor cells can replicate the processes of developmental differentiation, homeostatic self-renewal, and regeneration due to tissue damage, offering the potential to unravel the regulatory mechanisms of development and regeneration, and elucidate the pathophysiological processes involved in disease mechanisms. Herein, we have summarized the latest research on the production scheme of organ-specific iPSC-derived organoids, the contribution of these organoids in the treatment of various organ-related diseases, in particular their contribution to COVID-19 treatment, and have discussed the unresolved challenges and shortcomings of these models.

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

Cited by 6 publications

References 60 publications

Anticonstriction Effect of MCA in Rats by Danggui Buxue Decoction

Anticonstriction Effect of MCA in Rats by Danggui Buxue Decoction

Understanding genomic medicine for thoracic aortic disease through the lens of induced pluripotent stem cells

Merits and challenges of iPSC-derived organoids for clinical applications

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