Spatially defined microenvironment for engineering organoids DOI
Yilan Zhang,

Fukang Qi,

Peng Chen

et al.

Biophysics Reviews, Journal Year: 2024, Volume and Issue: 5(4)

Published: Oct. 18, 2024

In the intricately defined spatial microenvironment, a single fertilized egg remarkably develops into conserved and well-organized multicellular organism. This observation leads us to hypothesize that stem cells or other seed cell types have potential construct fully structured functional tissues organs, provided cues are appropriately configured. Current organoid technology, however, largely depends on spontaneous growth self-organization, lacking systematic guided intervention. As result, structures replicated in vitro often emerge disordered sparse manner during phases. Although existing organoids made significant contributions many aspects, such as advancing our understanding of development pathogenesis, aiding personalized drug selection, well expediting development, their creating large-scale implantable tissue organ constructs, constructing multicomponent microphysiological systems, together with functioning at metabolic levels remains underutilized. Recent discoveries demonstrated definition factors not only induces directional migration but also formation assembloids multiple regional identities. opens new avenues for innovative engineering higher-order organoids. Concurrently, organization microenvironmental cues, physical stresses, mechanical loads, material composition, has been minimally explored. review delves burgeoning field focus control. It offers insight molecular principles, expected outcomes, applications, envisioning future perspective this domain.

Language: Английский

Advances and Challenges in Modeling Autosomal Dominant Polycystic Kidney Disease: A Focus on Kidney Organoids DOI Creative Commons
Jinglan Gu, Fei Liu, Lu Li

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 523 - 523

Published: Feb. 19, 2025

Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent hereditary disorder characterized by distinct phenotypic variability that has posed challenges for advancing in-depth research. Recent advancements in organoid construction technologies have enabled researchers to simulate development and create simplified vitro experimental environments, allowing more direct observation of how genetic mutations drive pathological phenotypes disrupt physiological functions. Emerging technologies, such as microfluidic bioreactor culture systems single-cell transcriptomics, further supported the complex ADPKD organoids, offering robust models exploring mechanisms facilitating drug discovery. Nevertheless, significant remain constructing accurate models. This review will summarize recent advances construction, focusing on limitations current techniques critical issues need be addressed future breakthroughs. New Noteworthy: presents particularly iPSC-derived models, new insights into It focuses limited vascularization maturity, proposing potential solutions through emerging technologies. The ongoing optimization expected enhance understanding breakthroughs targeted therapy development.

Language: Английский

Citations

1
From organoids to organoids-on-a-chip: Current applications and challenges in biomedical research DOI Creative Commons
Kailun Liu,

Xiaowei Chen,

Zhen Fan

et al.

Chinese Medical Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract The high failure rates in clinical drug development based on animal models highlight the urgent need for more representative human biomedical research. In response to this demand, organoids and organ chips were integrated greater physiological relevance dynamic, controlled experimental conditions. This innovative platform—the organoids-on-a-chip technology—shows great promise disease modeling, discovery, personalized medicine, attracting interest from researchers, clinicians, regulatory authorities, industry stakeholders. review traces evolution organoids-on-a-chip, driven by necessity advanced biological models. We summarize applications of simulating pathological phenotypes therapeutic evaluation technology. section highlights how integrating technologies chips, such as microfluidic systems, mechanical stimulation, sensor integration, optimizes organoid cell types, spatial structure, functions, thereby expanding their applications. conclude addressing current challenges offering insights into prospects. advancement is poised enhance fidelity, standardization, scalability. Furthermore, integration cutting-edge interdisciplinary collaborations will be crucial progression

Language: Английский

Citations

0
CRISPR-Cas9 system in autosomal dominant polycystic kidney disease: a comprehensive review DOI Creative Commons

Se-Ki Kang,

Se Jin Park, Min Ho Lee

et al.

Childhood Kidney Diseases, Journal Year: 2025, Volume and Issue: 29(1), P. 4 - 11

Published: Feb. 28, 2025

Genetic kidney diseases are caused by mutations in specific genes that significantly affect development and function. Although the underlying pathogenic of many have been identified, an understanding their mechanisms effective treatments remains limited. Gene editing, particularly using clustered regularly interspaced short palindromic repeats (CRISPR), has recently become a promising approach for studying genetic CRISPR/CRISPR-associated protein 9 (CRISPR-Cas9) method prominent research method. It shown CRISPR-Cas9 can be targeted to knock out genomic sites, which enables researchers correct gene mutations, prevent inheritance, better understand function effectiveness drugs. However, application technology therapeutic agents against disease overlooked compared with other diseases. In this paper, we provide overview current advancements CRISPR technology, as well diverse preclinical methods implemented, particular emphasis on autosomal dominant polycystic disease.

Language: Английский

Citations

0
Gene Editing: An Effective Tool for the Future Treatment of Kidney Disease DOI Creative Commons
Meiling Cao, Ruirui Han,

Shungen Chen

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 4001 - 4018

Published: March 1, 2025

Gene editing technology involves modifying target genes to alter genetic traits and generate new phenotypes. Beginning with zinc-finger nucleases (ZFN) transcription activator-like effector (TALEN), the field has evolved through advent of clustered regularly interspaced short palindromic repeats CRISPR-associated protein (CRISPR-Cas) systems, more recently base editors (BE) prime (PE). These innovations have provided deep insights into molecular mechanisms complex biological processes paved way for novel therapeutic strategies a range diseases. is now being applied in treatment both acquired kidney diseases, as well transplantation correction mutations. This review explores current applications mainstream gene technologies biology, particular emphasis on their roles disease research of. It also addresses limitations challenges associated these technologies, while offering perspectives future potential this field.

Language: Английский

Citations

0
Axial Nephron Fate Switching Demonstrates a Plastic System Tunable on Demand DOI
MaryAnne Achieng, Jack Schnell,

Connor C. Fausto

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

The human nephron is a highly patterned tubular structure. It develops specialized cells that regulate bodily fluid homeostasis, blood pressure, and urine secretion throughout life. Approximately 1 million nephrons form in each kidney during embryonic fetal development, but how they develop poorly understood. Here we interrogate axial patterning mechanisms the using an iPSC-derived organoid system generates hundreds of developmentally synchronized nephrons, compare it to vivo development single cell spatial transcriptomic approaches. We show controlled by integrated WNT/BMP/FGF signaling. Imposing WNT ON /BMP OFF state established distal identity matures into thick ascending loop Henle endogenously activating FGF. Simultaneous suppression FGF signaling switches back proximal cell-state, transformation itself dependent on BMP signal transduction. Our highlights plasticity patterning, delineates roles WNT, FGF, mediated controlling paves way for generating demand.

Language: Английский

Citations

0
Generation of kidney organoids derived from human expanded potential stem cells DOI

Zhanpeng Kuang,

Changmiao Pang,

Haiyan Wang

et al.

Cells and Development, Journal Year: 2025, Volume and Issue: unknown, P. 204025 - 204025

Published: April 1, 2025

Language: Английский

Citations

0
Targeting Dysregulated Epigenetic Modifiers With Kidney‐Targeted Nanotherapeutics for Polycystic Kidney Disease DOI

Joshua Giblin,

Rüdiger Simon,

Jose Zarate‐Diaz

et al.

Journal of Biomedical Materials Research Part A, Journal Year: 2025, Volume and Issue: 113(4)

Published: April 1, 2025

ABSTRACT Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic worldwide. The one small molecule drug available to patients, tolvaptan, associated with off‐target side effects and high discontinuation rates, necessitating development of new therapeutic strategies. Previous work has shown that epigenome altered in ADPKD; however, identification targeting dysregulated epigenetic modulators yet be explored for human ADPKD therapy. Using cells derived from cysts we tested gene expression several modulators. We found Brd4 BMi1 are upregulated observed their inhibition using drugs, AZD‐5153 PTC‐209, significantly slowed proliferation patient cells. To enhance delivery PTC‐209 renal cells, loaded drugs into kidney‐targeting micelles (KM) assessed vitro. Combining KMs had a synergistic effect on reducing 3D PKD cyst model. These findings were also consistent murine vitro models Pkd1 null proximal tubule In summary, demonstrate as novel targets nanomedicine strategy ADPKD.

Language: Английский

Citations

0
Strategies to overcome the limitations of current organoid technology - engineered organoids DOI Creative Commons

Xulong Fan,

Kun Hou,

Gaojian Liu

et al.

Journal of Tissue Engineering, Journal Year: 2025, Volume and Issue: 16

Published: April 1, 2025

Organoids, as 3D in vitro models derived from stem cells, have unparalleled advantages over traditional cell and animal for studying organogenesis, disease mechanisms, drug screening, personalized diagnosis treatment. Despite the tremendous progress made organoid technology, translational application of organoids still presents enormous challenges due to complex structure function human organs. In this review, limitations technologies are first described. Next, we explore ways address many cultures by engineering various dimensions systems. Finally, discuss future directions field, including potential roles simulated microphysiology system We hope that review inspires research into system.

Language: Английский

Citations

0
Recent advances in extracellular matrix manipulation for kidney organoid research DOI Creative Commons

Ren Wang,

Yufei Sui, Qiuyan Liu

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 6, 2024

The kidney plays a crucial role in maintaining the body’s microenvironment homeostasis. However, current treatment options and therapeutic agents for chronic disease (CKD) are limited. Fortunately, advent of organoids has introduced novel vitro model studying diseases drug screening. Despite significant efforts been leveraged to mimic spatial-temporal dynamics fetal renal development various types organoids, there is still discrepancy cell maturity compared native tissue. extracellular matrix (ECM) regulating cellular signaling, which ultimately affects fate decision. As result, ECM can refine promoting their efficient differentiation maturation. This review examines existing techniques culturing evaluates strengths weaknesses assesses advancements limitations associated with utilization organoid culture. Additionally, it presents discussion on constructing specific physiological pathological microenvironments using decellularized during certain developmental stages or occurrences, aiding models.

Language: Английский

Citations

1
Fabry nephropathy: focus on podocyte damage and therapeutic target DOI Open Access
Dan Zhang, Kenan Xie, Jiong Zhang

et al.

Journal of Translational Genetics and Genomics, Journal Year: 2024, Volume and Issue: 8(4), P. 302 - 11

Published: Sept. 30, 2024

Fabry disease, a rare X-linked lysosomal storage disorder, is marked by deficiency in the activity of enzyme α-galactosidase A. This results accumulation globotriaosylceramide (Gb3) within various tissues and organs, which leads to life-threatening complications poor prognosis. Clinical manifestations are multisystemic, heterogeneous, progressive. Early diagnosis treatment great importance. nephropathy lesions characterized cell vacuolization glomeruli, tubules, interstitium, arteries ultrastructural myelin bodies. Kidney injury can occur structures, with podocytes being first be impacted due their low regeneration extensive exposure Gb3. The Gb3 causes podocytes, essential components glomerular cells, responsible for maintaining integrity filtration barrier. Enzyme replacement therapy, dynamic monitoring podocyte injury, research on repair mechanism will contribute overall kidney damage disease improve renal

Language: Английский

Citations

0