Advances and challenges toward developing kidney organoids for clinical applications

Cell stem cell, Год журнала: 2023, Номер 30(8), С. 1017 - 1027

Опубликована: Авг. 1, 2023

Язык: Английский

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The “3Ds” of Growing Kidney Organoids: Advances in Nephron Development, Disease Modeling, and Drug Screening

Cells, Год журнала: 2023, Номер 12(4), С. 549 - 549

Опубликована: Фев. 8, 2023

A kidney organoid is a three-dimensional (3D) cellular aggregate grown from stem cells in vitro that undergoes self-organization, recapitulating aspects of normal renal development to produce nephron structures resemble the native organ. These miniature kidney-like can also be derived primary patient and thus provide simplified context observe how mutations kidney-disease-associated genes affect organogenesis physiological function. In past several years, advances technologies have achieved formation organoids with enhanced numbers specialized cell types, less heterogeneity, more architectural complexity. Microfluidic bioreactor culture devices, single-cell transcriptomics, bioinformatic analyses accelerated sophisticated tailored them become increasingly amenable high-throughput experimentation. However, many significant challenges remain realizing use for replacement therapies. This review presents an overview field selected highlights recent cutting-edge research focus on embryonic development, modeling disease, personalized drug screening.

Язык: Английский

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Elucidating the Proximal Tubule HNF4A Gene Regulatory Network in Human Kidney Organoids

Journal of the American Society of Nephrology, Год журнала: 2023, Номер 34(10), С. 1672 - 1686

Опубликована: Июль 25, 2023

HNF4 genes promote proximal tubule differentiation in mice, but their function human nephrogenesis is not fully defined. This study uses pluripotent stem cell (PSC)-derived kidney organoids as a model to investigate HNF4A and HNF4G functions. The loss of , impaired reabsorption-related molecule expression microvilli formation tubules. Cleavage under targets release using nuclease (CUT&RUN) sequencing CRISPR-mediated transcriptional activation (CRISPRa) further confirm that directly regulates its target genes. Human provide good for studying regulation development.

Язык: Английский

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Kidney organoids reveal redundancy in viral entry pathways during ACE2-dependent SARS-CoV-2 infection

Journal of Virology, Год журнала: 2024, Номер 98(3)

Опубликована: Фев. 9, 2024

With a high incidence of acute kidney injury among hospitalized COVID-19 patients, considerable attention has been focussed on whether SARS-CoV-2 specifically targets cells to directly impact renal function, or damage is primarily an indirect outcome. To date, several studies have utilized organoids understand the pathogenesis COVID-19, revealing ability for predominantly infect proximal tubule (PT), with reduced infectivity following administration soluble ACE2. However, immaturity standard human represents significant hurdle, leaving preferred processing pathway, existence alternate viral receptors, and effect common hypertensive medications expression ACE2 in context exposure incompletely understood. Utilizing novel organoid model enhanced PT maturity, genetic- drug-mediated inhibition entry factors confirmed requirement but showed that virus can utilize dual spike protein pathways downstream receptor binding. These include TMPRSS- CTSL/CTSB-mediated non-endosomal endocytic pathways, TMPRSS10 likely playing more role pathway than TMPRSS2. Finally, treatment antihypertensive ACE inhibitor, lisinopril, negligible susceptibility infection. This study first in-depth characterization stem cell-derived PTs, providing deeper insight into implications ongoing pandemic.

Язык: Английский

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Heart and kidney organoids maintain organ-specific function in a microfluidic system

Materials Today Bio, Год журнала: 2023, Номер 23, С. 100818 - 100818

Опубликована: Сен. 25, 2023

Heart and kidney communicate with one another in an interdependent relationship they influence each other's behavior reciprocally, as pathological changes organ can damage the other. Although independent human vitro models for heart exist, do not capture their dynamic crosstalk. We have developed a microfluidic system which be used to study interaction vitro. Cardiac microtissues (cMTs) organoids (kOs) derived from induced pluripotent stem cells (hiPSCs) were generated loaded into two separated communicating chambers of perfusion chip. Static culture conditions compared under unidirectional flow. Tissue viability was maintained minimally 72 h both conditions, indicated by presence sarcomeric structure coupled beating activity cMTs nephron structures albumin uptake kOs. concluded that this enables cardiac organoid while controlling parameters like fluidic flow speed direction. Together, "cardiorenal-unit" provides new model cardiorenal axis it may further investigate diseases involving organs potential treatments.

Язык: Английский

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Metabolic Rewiring and Communication: An Integrative View of Kidney Proximal Tubule Function

Annual Review of Physiology, Год журнала: 2023, Номер 86(1), С. 405 - 427

Опубликована: Ноя. 28, 2023

The kidney proximal tubule is a key organ for human metabolism. responds to stress with altered metabolite transformation and perturbed metabolic pathways, an ultimate cause disease. Here, we review the tubule's function through integrative view of transport, metabolism, function, embed it in context metabolome-wide data-driven research. Function (filtration, secretion, reabsorption), transformation, signaling determine rewiring Energy metabolism substrates pathways are orchestrated by sensors. Given importance renal inner milieu, also communication routes other organs. Exciting research opportunities exist understand perturbation example, hypertension-associated We argue that, based on outlined here, diseases without genetic should be approached scientifically as diseases.

Язык: Английский

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Generation of proximal tubule-enhanced kidney organoids from human pluripotent stem cells

Nature Protocols, Год журнала: 2023, Номер 18(11), С. 3229 - 3252

Опубликована: Сен. 28, 2023

Язык: Английский

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Organoid assessment technologies

Clinical and Translational Medicine, Год журнала: 2023, Номер 13(12)

Опубликована: Дек. 1, 2023

Abstract Despite enormous advances in the generation of organoids, robust and stable protocols organoids are still a major challenge to researchers. Research for assessing structures evaluations their functions on vitro or vivo is often limited by precision strategies. A growing interest has arisen, aimed at standardizing process obtaining accurately resemble human‐derived tissue. The complex microenvironment intricate cellular crosstalk, organ‐specific architectures further complicate urgently quest high‐through schemes. By utilizing multi‐omics analysis single‐cell analysis, cell‐cell interaction mechanisms can be deciphered, investigated detailed view histological analysis. In this review, we will conclude novel approaches study molecular mechanism cell heterogeneity discuss morphological similarity comparison human body. Future perspectives functional developed become mature models.

Язык: Английский

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Highly parallel production of designer organoids by mosaic patterning of progenitors

Cell Systems, Год журнала: 2024, Номер 15(7), С. 649 - 661.e9

Опубликована: Июль 1, 2024

Язык: Английский

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Complex in vitro models positioned for impact to drug testing in pharma: a review

Biofabrication, Год журнала: 2024, Номер 16(4), С. 042006 - 042006

Опубликована: Авг. 27, 2024

Abstract Recent years have seen the creation and popularization of various complex in vitro models (CIVMs), such as organoids organs-on-chip, a technology with potential to reduce animal usage pharma while also enhancing our ability create safe efficacious drugs for patients. Public awareness CIVMs has increased, part, due recent passage FDA Modernization Act 2.0. This visibility is expected spur deeper investment adoption models. Thus, end-users model developers alike require framework both understand readiness current enter drug development process, assess upcoming same. review presents selection based on comparative -omics data (which we term model-omics), metrics qualification specific test assays that may support context-of-use (COU) assays. We surveyed existing healthy tissue ten development-critical organs body, provide evaluations suggestions improving model-omics COU each. In whole, this comes from perspective, seeks an evaluation where are poised maximum impact roadmap realizing potential.

Язык: Английский

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