MTMLab Research Summary: Improving Lab-Grown Liver Cell Maturation


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Our latest study addresses a critical challenge in liver tissue engineering: stem cell-derived liver cells (iHeps) typically remain functionally immature, limiting their usefulness for drug testing and disease modeling.

Our research team created 3D microtissues using droplet microfluidics technology by:

• Encapsulating iHeps in tiny collagen gel droplets (~250 μm diameter)

• Coating these structures with various non-parenchymal cells (NPCs)

• Testing different combinations and sequences of supporting cells

Key findings:

1) Embryonic fibroblasts and liver sinusoidal endothelial cells (LSECs) produced the most mature iHeps compared to other tested cell types

2) Sequential application of cell signals (embryonic fibroblasts first, then LSECs) yielded optimal maturation

3) Specific growth factors like stromal-derived factor-1 alpha were identified as important maturation enhancers

4) Gene expression analysis confirmed that LSEC/iHep microtissues closely resembled adult human liver cells

This platform enables researchers to identify critical cellular interactions and molecular signals that drive liver cell maturation, providing valuable insights for developing more physiologically relevant liver models for drug screening and regenerative medicine applications.


https://www.sciencedirect.com/science/article/pii/S174270612500193X

SIMPLE SUMMARY:

Embryonic fibroblasts and liver sinusoidal endothelial cells dramatically improved iHep maturation compared to other cell types tested, producing more functionally mature liver cells.

Sequential application proved crucial—adding embryonic fibroblasts first, followed by endothelial cells, yielded optimal maturation. Specific growth factors including stromal-derived factor-1 enhanced this process.

This research enables creation of more authentic mini-liver tissues that function like human liver. These improved models support better drug testing, disease research, and regenerative medicine applications.

Top 5 Latest Advances in Stem Cell Applications for Tissue Engineering

December 13, 2024
1. Three-Dimensional (3D) Cell Culture Techniques : New 3D cell culture methods have significantly improved the properties of stem cells, enhancing their viability and functionality for tissue regeneration. These techniques allow for more accurate modeling of tissue architecture and function. 2. Engineered Stem Cells : Advances in bioengineering have led to the development of "engineered stem cells," which are modified to enhance their regenerative capabilities. These next-generation stem cells are designed to be more effective in tissue repair and regeneration. 3. Injectable Biomimetic Hydrogels : Researchers have developed advanced injectable hydrogels that mimic natural tissue environments. These hydrogels hold significant promise for tissue engineering applications, providing a supportive matrix for stem cell growth and differentiation. 4. Integration with Tissue Scaffolds : There have been significant improvements in integrating stem cells with biomaterial scaffolds. These scaffolds provide structural support and enhance the differentiation and growth of stem cells into specific tissue types, improving the outcomes of regenerative treatments. 5. Gene Editing and mRNA Technologies : Techniques like CRISPR and mRNA-based therapies are being used to modify stem cells at the genetic level, enhancing their ability to regenerate tissues. These technologies allow for precise control over stem cell behavior and function.

MTM Lab's Accomplishments - Driven by Empowering Innovations

December 13, 2024
The MTM lab has experienced considerable growth over the last several years at the University of Illinois Chicago!

Grants Awarded to the MTM Laboratory

December 12, 2024
2024 The MTM Lab has been awarded an NIDDK R01 (National Institute of Diabetes and Digestive and Kidney Diseases) grant to develop a novel microfluidic approach to elucidate the effects of soluble factor gradients, individually and in controlled combinations, on zonated functions in primary liver cells from rodents and humans towards determining species-specific effects . Ultimately, our novel devices can be used to investigate the mechanisms underlying liver zonation, chemical-induced zonated hepatotoxicity, and how zonation is perturbed in liver diseases, such as non-alcoholic fatty liver disease and hepatocellular carcinoma. The MTM Lab has been awarded a NIEHS (National Institute of Environmental Health Sciences) grant to develop a high throughput system to test placental cell invasion using a 3D placental microtissue coupled with hepatic liver biotransformation . This first-of-its-kind hepatic-placenta organ-tandem on a chip will simulate the liver metabolism that chemicals undergo in vivo prior to reaching the placental bed. This state-of-the-art in vitro platform will be the first step towards incorporating organism-level organization into reproductive risk assessment using a non-animal-based approach. The MTM Lab has been awarded a NIEHS (National Institute of Environmental Health Sciences) grant to develop a human gut-liver platform with microbiome interactions for in vitro toxicology . These first-of-its-kind scalable human gut-liver models will be developed for in vitro applications, such as compound screening and disease modeling, and be used to elucidate the effects of reciprocal tissue crosstalk on cell phenotype modulation. 2023 The MTM Lab has been awarded a NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) grant to analyze the synergistic effects of extracellular matrix composition and stiffness, multicellular interactions, and soluble triggers of NAFLD in cellular phenotypic alterations , which could aid the development of novel drug therapies for this disease. The MTM Lab has been awarded a NIAAA (National Institute on Alcohol Abuse and Alcoholism) grant to develop a first-of-its-kind organotypic mouse liver model and investigate the effects of alcohol on multiple liver cell types in this model with comparisons to an in vivo mouse model of ALD that recapitulates several key features of human ALD. This platform can aid in understanding the molecular mechanisms underlying alcohol-associated liver disease.
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