Optogenetics: Background, Methodological Advances and Potential Applications for Cardiovascular Research and Medicine

Frontiers in Bioengineering and Biotechnology, Год журнала: 2020, Номер 7

Опубликована: Янв. 28, 2020

Optogenetics is an elegant approach of precisely controlling and monitoring the biological functions a cell, group cells, tissues or organs with high temporal spatial resolution by using optical system genetic engineering technologies. The field evolved need to control neurons decipher neural circuity has made great accomplishments in neuroscience. It also cardiovascular research almost decade ago considerable progress both vitro vivo animal studies. Thus, this review written objective provide information on evolution, background, methodical advances, potential scope for medicine. We begin literatures optogenetic proteins related their origin, structure, types, mechanism action, methods improve performance, delivery vehicles express such target cells research. Next, we reviewed historical recent demonstrate optogenetics medicine, as cardiac physiological functions, pacing hearts manipulating heart functions. examined that modality vital mimicking diseases, understanding mechanisms disease progression introducing novel therapies treat abnormalities, arrhythmias. promising tool providing high-throughput data cardiotoxicity screening drug development. Finally, put forth considerations scaling up system, clinically relevant silico models, light attenuation issues, concerns over level, immune reactions, toxicity, ectopic expression opsin expression. Detailed investigations would accelerate translation from present studies clinical therapies.

Язык: Английский

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Bioengineering in vitro models of embryonic development

Stem Cell Reports, Год журнала: 2021, Номер 16(5), С. 1104 - 1116

Опубликована: Май 1, 2021

Stem cell-based in vitro models of embryonic development have been established over the last decade. Such model systems recapitulate aspects gametogenesis, early development, or organogenesis. They enable experimental approaches that not possible previously and potential to greatly reduce number animals required for research. However, each system has its own limitations, with certain aspects, such as morphogenesis spatiotemporal control cell fate decisions, diverging from vivo counterpart. Targeted bioengineering provide defined instructive external signals modulate internal cellular could overcome some these limitations. Here, we present latest technical developments discuss how can further advance optimization stem embryo-like structures (ELSs). In combined sophisticated tools will an even more in-depth analysis future.

Язык: Английский

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Sculpting with stem cells: how models of embryo development take shape

Development, Год журнала: 2021, Номер 148(24)

Опубликована: Дек. 15, 2021

ABSTRACT During embryogenesis, organisms acquire their shape given boundary conditions that impose geometrical, mechanical and biochemical constraints. A detailed integrative understanding how these morphogenetic information modules pattern the mammalian embryo is still lacking, mostly owing to inaccessibility of in vivo for direct observation manipulation. These impediments are circumvented by developmental engineering embryo-like structures (stembryos) from pluripotent stem cells easy access, track, manipulate scale. Here, we explain unlocking distinct levels architecture through controlled modulations cellular environment enables identification minimal sets inputs necessary embryo. We detail this can be complemented with precise measurements manipulations tissue biochemistry, mechanics geometry across spatial temporal scales provide insights into mechanochemical feedback loops governing morphogenesis. Finally, discuss how, even absence active manipulations, stembryos display intrinsic phenotypic variability leveraged define constraints ensure reproducible morphogenesis vivo.

Язык: Английский

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Rapid Optogenetic Clustering in the Cytoplasm with BcLOVclust

Journal of Molecular Biology, Год журнала: 2024, Номер 436(3), С. 168452 - 168452

Опубликована: Янв. 21, 2024

Язык: Английский

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Nano-optogenetics for Disease Therapies

ACS Nano, Год журнала: 2024, Номер 18(22), С. 14123 - 14144

Опубликована: Май 20, 2024

Optogenetic, known as the method of 21 centuries, combines optic and genetic engineering to precisely control photosensitive proteins for manipulation a broad range cellular functions, such flux ions, protein oligomerization dissociation, intercommunication, so on. In this technique, light is conventionally delivered targeted cells through optical fibers or micro light-emitting diodes, always suffering from high invasiveness, wide-field illumination facula, strong absorption, scattering by nontargeted endogenous substance. Light-transducing nanomaterials with advantages spatiotemporal resolution, abundant wireless-excitation manners, easy functionalization recognition specific cells, recently have been widely explored in field optogenetics; however, there remain few challenges restrain its clinical applications. This review summarized recent progress on light-responsive genetically encoded myriad activation strategies use light-transducing their disease-treatment applications, which expected sparking helpful thought push forward preclinical translational uses.

Язык: Английский

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Signaling, Deconstructed: Using Optogenetics to Dissect and Direct Information Flow in Biological Systems

Annual Review of Biomedical Engineering, Год журнала: 2021, Номер 23(1), С. 61 - 87

Опубликована: Март 16, 2021

Cells receive enormous amounts of information from their environment. How they act on this information-by migrating, expressing genes, or relaying signals to other cells-comprises much the regulatory and self-organizational complexity found across biology. The "parts list" involved in cell signaling is generally well established, but how do these parts work together decode produce appropriate responses? This fundamental question increasingly being addressed with optogenetic tools: light-sensitive proteins that enable biologists manipulate interaction, localization, activity state high spatial temporal precision. In review, we summarize optogenetics used pursuit an answer question, outlining current suite tools available researcher calling attention studies increase our understanding improve ability engineer

Язык: Английский

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Reverse engineering human brain evolution using organoid models

Brain Research, Год журнала: 2019, Номер 1729, С. 146582 - 146582

Опубликована: Дек. 3, 2019

Язык: Английский

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Optogenetic Control of the BMP Signaling Pathway

ACS Synthetic Biology, Год журнала: 2020, Номер 9(11), С. 3067 - 3078

Опубликована: Окт. 21, 2020

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor β (TGFβ) superfamily and have crucial roles during development; including mesodermal patterning specification renal, hepatic, skeletal tissues. In vitro developmental models currently rely upon costly unreliable recombinant BMP that do not enable dynamic or precise activation signaling pathway. Here, we report development an optogenetic system (optoBMP) enables rapid induction canonical pathway driven by illumination with blue light. We demonstrate utility optoBMP in multiple human cell lines to initiate signal transduction through phosphorylation nuclear translocation SMAD1/5, leading upregulation target genes Inhibitors DNA binding ID2 ID4. Furthermore, how can be used fine-tune variable light stimulation. Optogenetic control will high-throughput intervention across a variety applications cellular systems.

Язык: Английский

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Directed differentiation of human iPSCs into mesenchymal lineages by optogenetic control of TGF-β signaling

Cell Reports, Год журнала: 2023, Номер 42(5), С. 112509 - 112509

Опубликована: Май 1, 2023

In tissue development and homeostasis, transforming growth factor (TGF)-β signaling is finely coordinated by latent forms matrix sequestration. Optogenetics can offer precise dynamic control of cell signaling. We report the an optogenetic human induced pluripotent stem system for TGF-β demonstrate its utility in directing differentiation into smooth muscle, tenogenic, chondrogenic lineages. Light-activated resulted expression markers at levels close to those soluble factor-treated cultures, with minimal phototoxicity. a cartilage-bone model, light-patterned gradients allowed establishment hyaline-like layer cartilage articular surface while attenuating depth enable hypertrophic induction osteochondral interface. By selectively activating co-cultures light-responsive non-responsive cells, undifferentiated differentiated cells were simultaneously maintained single culture shared medium. This platform patient-specific spatiotemporally studies cellular decision making.

Язык: Английский

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Stem Cell and Synthetic Embryo Models: Advances, Applications, and Ethical Considerations

Stem Cell Reviews and Reports, Год журнала: 2025, Номер unknown

Опубликована: Май 20, 2025

Abstract Independent traditional gametes and recent advances in stem cell biology have made it possible to create synthetic embryo models (SEMs), altering our capacity study early human development, congenital diseases, regenerative medicine. By recreating key developmental events vitro, these provide unmatched insights into embryogenesis creative platforms for disease modeling, drug discovery, individualized therapy. The quick development SEM research raises serious ethical, legal, regulatory questions that call creating transparent control systems. methods applied fabrication, their biomedical applications, the moral issues connected with use are investigated this review. We also look at future directions, including enhancing ethical frameworks, adding artificial intelligence, increasing model fidelity, encouraging public participation. Through multidisciplinary cooperation, SEMs might address problems transform biology, advancing scientific advancement.

Язык: Английский

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