Liver organoids: Current advances and future applications for hepatology DOI Creative Commons
Yohan Kim, Minseok Kang, Michael Girma Mamo

et al.

Clinical and Molecular Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 26, 2024

The creation of self-organizing liver organoids represents a significant, although modest, step toward addressing the ongoing organ shortage crisis in allogeneic transplantation.However, researchers have recognized that achieving fully functional whole remains distant goal, and original ambition organoid-based generation has been temporarily put on hold.Instead, revolutionized field hepatology, extending their influence into various domains precision molecular medicine.These 3D cultures, capable replicating key features human function pathology, opened new avenues for human-relevant disease modeling, CRISPR gene editing, high-throughput drug screening animal models cannot accomplish.Moreover, advancements creating more complex systems led to development multicellular assembloids, dynamic organoid-on-chip systems, bioprinting technologies.These innovations enable detailed modeling microenvironments tissue interactions.Progress regenerative medicine transplantation applications continues evolve strives overcome obstacles biocompatibility tumorigenecity.In this review, we examine current state organoid research by offering insights where currently stands, pivotal developments are driving its shaping future.and difficulties screening, which is one advantages 2D cell culture 15 .Given limitations models, such as organoids, spheroids, bioprinting, recently emerged promising technologies address these challenges.Spheroids represent simplest form culture, allowing formation spherical structures through aggregation without need extracellular matrix (ECM) components Matrigel 16- 20 .Their simplicity enables easy culturing, they widely studied types aggregate well, cancer cells, embryoid bodies, hepatocytes.However, most spheroids solid structures, limits ability replicate specific structural characteristics organs.Additionally, delivery nutrients oxygen cells at center spheroid challenging, often resulting necrosis other 17,20,21 .In manuscript, aim focus systems.In 2008, when self-organized apico-basally polarized cortical were reported from embryonic stem (ESCs) 22 , Lgr5-positive isolated adult intestinal shown cryptvillus structure self-organization 23 studies expansion methods published.Organoids formed (ASCs), pluripotent (PSCs) or progenitor recapitulate target functions 24 .Organoids actively utilized across fields because incorporate traditional experimental genetic manipulation, replication physiological 25 .ASC-derived isolating primary tissues culturing them under signaling conditions respective organ, maintain structural, physiological, 23,[26][27][28] .These ASC-organoid stability even after long-term 26 and, can be generated patient-derived hold potential personalized medicine, toxicity assessments therapy.However, requirement invasive procedures obtain patient considered drawback.On hand, PSC-derived using relatively less offer advantage generating organs, brain, samples difficult [29][30][31][32] .Brain predominantly conducted induced-pluripotent (iPSC)-derived particularly patient-specific organoids.However, differentiation processes required generate major source high variability among 33,34 .Additionally, differences between PSC lines another concern.Despite challenges, both ASC-derived effectively vivo organs vitro applications.By leveraging strengths each source, effective tailored conducted.

Language: Английский

Applications of Artificial Intelligence in Drug Repurposing DOI Creative Commons
Zhaoman Wan,

Xinran Sun,

Yi Li

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Drug repurposing identifies new therapeutic uses for the existing drugs originally developed different indications, aiming at capitalizing on established safety and efficacy profiles of known drugs. Thus, it is beneficial to bypass early stages drug development, reduction time cost associated with bringing therapies market. Traditional experimental methods are often time-consuming expensive, making artificial intelligence (AI) a promising alternative due its lower cost, computational advantages, ability uncover hidden patterns. This review focuses availability AI algorithms in their positive specific roles revealing drugs, especially being integrated virtual screening. It shown that excel analyzing large-scale datasets, identifying complicated patterns responses from these predictions potential repurposing. Building insights, challenges remain developing efficient future research, including integrating drug-related data across databases better repurposing, enhancing efficiency, advancing personalized medicine.

Language: Английский

Citations

1
Decellularized Liver Matrices for Expanding the Donor Pool—An Evaluation of Existing Protocols and Future Trends DOI Creative Commons
Marcin Morawski, Maciej Krasnodębski, Jakub Rochoń

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 98 - 98

Published: Jan. 10, 2025

Liver transplantation is the only curative option for end-stage liver disease and necessary an increasing number of patients with advanced primary or secondary cancer. Many patient groups can benefit from this treatment, however shortage grafts remains unsolved problem. bioengineering offers a promising method expanding donor pool through production acellular scaffolds that be seeded recipient cells. Decellularization protocols involve removal cells using various chemical, physical, enzymatic steps to create collagenous network provides support introduced future vascular biliary beds. However, causes varying degrees matrix damage, affect cell seeding organ performance. The main objective review present existing techniques producing decellularized livers, emphasis on assessment definition acellularity. agents are discussed, standard process evaluated. We also introduce concept stepwise during decellularization cycles. This may lead shorter detergent exposure times less scaffold damage. introduction apoptosis induction in field engineering provide valuable alternative long perfusion protocols, which significant A thorough understanding action factors influencing final composition essential produce biocompatible matrix, basis further studies regarding recellularization retransplantation.

Language: Английский

Citations

0
Conjugation of PDLA onto MgO Microspheres: Comparison between Solution Grafting and Melt Grafting Methods DOI
Wenhao Yu, Dong Zhou, Fangrui Liu

et al.

Journal of Materials Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

MgO microspheres modified by solution and melt grafting methods were used to assess the effect of reaction temperature on PDLA graft ratio, resulting in varied surface morphologies controllable degradability when analyzed kinetic modeling.

Language: Английский

Citations

0
The P2X7-Mediated Mitochondrial ROS as an Emerging Core Target of Tuftsin Nanoparticles in Severe Acute Pancreatitis Therapy via Regulating Mitophagy DOI
E Wen, Yu Tian,

Mingxiao Fang

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

20% acute pancreatitis (AP) develops into severe AP (SAP), a global health crisis, with an increased mortality rate to 30%–50%. Mitochondrial damage and immune disorders are direct factors, which exacerbate the occurrence progression of AP. So far, mitochondrial immunity injury in SAP remains largely elusive, no established treatment options available. Immunomodulation is promising approach treat pancreatitis. Herein, we proved that Tuftsin (TN), vital endogenous immunomodulator, can inhibit SAP, while it limited by extremely short biological half-life, low bioavailability, inconvenience administration. Nano platform positive choice. Interestingly, found activated P2X7 signaling was closely associated enhanced pancreatic inflammation via damaging function SAP. engineered nanoplatform containing Se–Se bond responsive for ROS deliver TN, namely, DSPE–Se-Se-MPEG@TN (DSSM@TN), contributing increases TN's half-life bioavailability. We synthesized TN-loaded ROS-responsive DSPE–Se-Se- MPEG@TN liposomes (DSSM@TN NPs) one-step emulsification method, exhibited good biosecurity, high stability, suitable size, favorable responsiveness biocompatibility, as well excellent capability releasing TN during oxidative stress environment. Moreover, ability first play role enhance its anti-inflammation antioxidant abilities targeting damaged mitochondria progression. Mechanistically, DSSM@TN pancreas simultaneously inhibits dysfunction vivo vitro signaling-impaired Nrf2/HO-1 signaling-inhibited PINK1/PARKIN pathway. Consequently, such immunotherapy nanomedicine targeted holds great potential facilitating substantial clinical progress treatment.

Language: Английский

Citations

0
Liver organoids: Current advances and future applications for hepatology DOI Creative Commons
Yohan Kim, Minseok Kang, Michael Girma Mamo

et al.

Clinical and Molecular Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 26, 2024

The creation of self-organizing liver organoids represents a significant, although modest, step toward addressing the ongoing organ shortage crisis in allogeneic transplantation.However, researchers have recognized that achieving fully functional whole remains distant goal, and original ambition organoid-based generation has been temporarily put on hold.Instead, revolutionized field hepatology, extending their influence into various domains precision molecular medicine.These 3D cultures, capable replicating key features human function pathology, opened new avenues for human-relevant disease modeling, CRISPR gene editing, high-throughput drug screening animal models cannot accomplish.Moreover, advancements creating more complex systems led to development multicellular assembloids, dynamic organoid-on-chip systems, bioprinting technologies.These innovations enable detailed modeling microenvironments tissue interactions.Progress regenerative medicine transplantation applications continues evolve strives overcome obstacles biocompatibility tumorigenecity.In this review, we examine current state organoid research by offering insights where currently stands, pivotal developments are driving its shaping future.and difficulties screening, which is one advantages 2D cell culture 15 .Given limitations models, such as organoids, spheroids, bioprinting, recently emerged promising technologies address these challenges.Spheroids represent simplest form culture, allowing formation spherical structures through aggregation without need extracellular matrix (ECM) components Matrigel 16- 20 .Their simplicity enables easy culturing, they widely studied types aggregate well, cancer cells, embryoid bodies, hepatocytes.However, most spheroids solid structures, limits ability replicate specific structural characteristics organs.Additionally, delivery nutrients oxygen cells at center spheroid challenging, often resulting necrosis other 17,20,21 .In manuscript, aim focus systems.In 2008, when self-organized apico-basally polarized cortical were reported from embryonic stem (ESCs) 22 , Lgr5-positive isolated adult intestinal shown cryptvillus structure self-organization 23 studies expansion methods published.Organoids formed (ASCs), pluripotent (PSCs) or progenitor recapitulate target functions 24 .Organoids actively utilized across fields because incorporate traditional experimental genetic manipulation, replication physiological 25 .ASC-derived isolating primary tissues culturing them under signaling conditions respective organ, maintain structural, physiological, 23,[26][27][28] .These ASC-organoid stability even after long-term 26 and, can be generated patient-derived hold potential personalized medicine, toxicity assessments therapy.However, requirement invasive procedures obtain patient considered drawback.On hand, PSC-derived using relatively less offer advantage generating organs, brain, samples difficult [29][30][31][32] .Brain predominantly conducted induced-pluripotent (iPSC)-derived particularly patient-specific organoids.However, differentiation processes required generate major source high variability among 33,34 .Additionally, differences between PSC lines another concern.Despite challenges, both ASC-derived effectively vivo organs vitro applications.By leveraging strengths each source, effective tailored conducted.

Language: Английский

Citations

0