Expandable, Functional Hepatocytes Derived from Primary Cells Enable Liver Therapeutics DOI Creative Commons

Sunil K. Mallanna,

Soujanya S. Karanth,

Joseph E. Marturano

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

Abstract Liver disease affects millions annually in the United States, with orthotopic transplantation as only curative option for many patients. However, scarcity of donor organs highlights a need alternative cell-based therapies. Hepatocyte-based approaches are promising due to cells’ inherent synthetic, metabolic, and detoxifying functions, but they face critical barriers, including lack scalable source functional hepatocytes poor engraftment. In this study, we developed process expanding primary human (PHHs) while preserving their identity function. By leveraging heterocellular aggregation stromal cells, generated cryopreserved “seed” constructs that maintained viability function post-thaw. Seeds demonstrated enhanced metabolic detoxification functions robust engraftment across multiple anatomic sites outside liver. Our approach addresses key limitations hepatocyte-based therapies, offering stable, scalable, clinically viable platform liver cell therapy applications.

Language: Английский

Current hPSC-derived liver organoids for toxicity testing: Cytochrome P450 enzymes and drug metabolism DOI Creative Commons
Hyemin Kim, Han‐Jin Park

Toxicological Research, Journal Year: 2025, Volume and Issue: 41(2), P. 105 - 121

Published: Jan. 3, 2025

Language: Английский

Citations

3
Therapeutic potential of stem cells in regeneration of liver in chronic liver diseases: Current perspectives and future challenges DOI
Poonam Yadav, Sumeet Kumar Singh,

Sonu Rajput

et al.

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 253, P. 108563 - 108563

Published: Nov. 26, 2023

Language: Английский

Citations

16
Transforming Toxicity Assessment through Microphysiology, Bioprinting, and Computational Modeling DOI Open Access

Tamer A. Addissouky

Advances in Clinical Toxicology, Journal Year: 2024, Volume and Issue: 9(1), P. 1 - 14

Published: Jan. 1, 2024

Background: Traditional toxicity testing emphasizes animal models with growing concerns regarding predictive capacity, throughput and ethics. Rapid innovation surrounding human cell platforms, bioengineered tissues, omics techniques computational tools offers more modern alternatives aligned expanding knowledge of chemical biological pathways. These disruptive approaches promise immense potential to transform next-generation safety assessment drug development pipelines. Purpose: This review provides clinical researchers an updated, comprehensive perspective across evolving areas focus in new methods analysis latest advances translational context. Main Body: We survey progress two- three-dimensional cultures recapitulating tissue/organ complexity impossible conventional assays. Complementing this, modeling integrates structure-activity relationships, physicochemical properties physiological interactions predict pharmacokinetics silico. Expanding model organisms add further dimensionality demographic relevance. High-throughput imaging technologies unravel mechanisms illuminate biomarkers undetectable by standard measures. Specialized show high addressing toxicodynamic intricacies within disease contexts like diabetes NAFLD. Evaluating traditional medicines phytochemicals likewise represents area growth well-suited for contemporary platforms. Future outlook weighs remarkable advantages reducing demands, enabling precision toxicology links medicine overhauling core risk frameworks. Conclusion: intends catalyze discourse on strategic optimization priorities roadmaps towards fully unlocking the yet still emerging public health these poising transformation sciences centered human-focused models.

Language: Английский

Citations

6
Neuropharmacology in the Molecular Epoch DOI

Neelakanta Sarvashiva Kiran,

Chandrashekar Yashaswini,

Bhupendra G. Prajapati

et al.

Published: April 17, 2025

Language: Английский

Citations

0
Developments and Applications of Liver-on-a-Chip Technology—Current Status and Future Prospects DOI Creative Commons
Joseph Mugaanyi, Jing Huang, Jiongze Fang

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(6), P. 1272 - 1272

Published: May 22, 2025

Background/Objectives: Liver-on-a-chip (LiOC) technology is increasingly recognized as a transformative platform for modeling liver biology, disease mechanisms, drug metabolism, and toxicity screening. Traditional two-dimensional (2D) in vitro models lack the complexity needed to replicate liver’s unique microenvironment. This review aims summarize recent advancements LiOC systems, emphasizing their potential biomedical research translational applications. Methods: narrative synthesizes findings from key studies on development application of platforms. We explored innovations material science bioengineering, including microfluidic design, 3D printing, stem cell– tissue-derived organoid integration, co-culture strategies. Commercially available systems regulatory relevance were also evaluated. Results: have evolved simple PDMS-based chips complex, multicellular constructs incorporating hepatocytes, endothelial cells, Kupffer hepatic stellate cells. Recent demonstrate superior ability liver-specific architecture functions. Applications span cancer research, assessment (e.g., drug-induced injury prediction with >85% sensitivity), modeling, regenerative medicine. Several platforms gained FDA recognition are active use preclinical testing. Conclusions: offers more physiologically relevant alternative traditional holds promise reducing reliance animal studies. While challenges remain, such vascularization long-term function, ongoing paving way toward clinical pharmaceutical integration. The poised play role personalized medicine next-generation therapeutic development.

Language: Английский

Citations

0
Expandable, Functional Hepatocytes Derived from Primary Cells Enable Liver Therapeutics DOI Creative Commons

Sunil K. Mallanna,

Soujanya S. Karanth,

Joseph E. Marturano

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

Abstract Liver disease affects millions annually in the United States, with orthotopic transplantation as only curative option for many patients. However, scarcity of donor organs highlights a need alternative cell-based therapies. Hepatocyte-based approaches are promising due to cells’ inherent synthetic, metabolic, and detoxifying functions, but they face critical barriers, including lack scalable source functional hepatocytes poor engraftment. In this study, we developed process expanding primary human (PHHs) while preserving their identity function. By leveraging heterocellular aggregation stromal cells, generated cryopreserved “seed” constructs that maintained viability function post-thaw. Seeds demonstrated enhanced metabolic detoxification functions robust engraftment across multiple anatomic sites outside liver. Our approach addresses key limitations hepatocyte-based therapies, offering stable, scalable, clinically viable platform liver cell therapy applications.

Language: Английский

Citations

0