Internationally Recognized Research in Cell and Tissue Engineering
MTM Lab strives for transformative impact by creating engineered tissues for applications in drug development, disease modeling, and regenerative medicine (cell-based therapies).
Our mission is to improve people's lives by helping to create tools and better treatments to combat adverse drug effects and chronic organ diseases.
Director: Salman R. Khetani, PhD
UNLOCK YOUR POTENTIAL
Join our vibrant team of researchers and gain access to cutting-edge cell and tissue engineering research, advanced academic opportunities, and job placements in industry and academia.
What's new & exciting
𝗦𝗶𝗺𝗽𝗹𝗲 𝗦𝘂𝗺𝗺𝗮𝗿𝘆: This study explores how we can improve lab-grown liver cells for medical research and drug testing. The MTMLab team works with induced pluripotent stem cells (iPSCs) - special cells that can be transformed into liver-like cells - because real human liver cells are hard to obtain. However, these lab-grown liver cells don't function as well as mature adult liver cells. The research team discovered that the surface environment where these cells grow is crucial for their development. We created tiny fiber scaffolds made from different materials like collagen, decellularized livers, and chitosan that mimic the natural structure around liver cells. When liver cells were grown on these specially designed nanofibers for three weeks, they displayed higher function compared to cells grown on standard surfaces. Our key finding was that both the material composition and the nanoscale fiber structure were important - stiffer synthetic fibers or softer materials without the appropriate topography or composition prevented proper cell maturation. This research helps create better lab models of human liver tissue that can be used for testing new drugs and studying liver diseases more effectively.
Owen Lally Modeling the synergistic effects of alcohol and fats on liver disease via engineered cocultures In Vitro Liver Toxicology Testing of Rat and Dog Hepatocytes to Reduce In Vivo Regulatory Requirements Nathan Shelton Enhancing the Functions and Hepatitis B Virus Infectability of Primary Human Hepatocytes Protein Microarrays to Probe Synergistic Effects of Extracellular Matrix Composition and Stiffness on Liver Macrophages Lesly Villarreal Engineering a 3D Placental Trophoblast Invasion Platform Via Droplet Microfluidics Gas-permeable Plates to Model Synergetic Effects of Oxygen and Endothelial Factors on Liver Zonation Emanuele Spanghero Modeling the Interplay Between Liver and Heart Diseases via a Human Dual-Organ Platform Engineering High Cell Density Beating Cords of Cardiomyocytes and Fibroblasts via Photopatterned Alginate
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.
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.
The MTM lab has experienced considerable growth over the last several years at the University of Illinois Chicago!
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.
List of Services
-
Engineered microtissues to model the effects of dynamic heterotypic cell signaling on iPSC-derived human hepatocyte maturation
Regeant Panday, Kerry M. Rogy, Yong Duk Han, Salman R. Khetani, Engineered microtissues to model the effects of dynamic heterotypic cell signaling on iPSC-derived human hepatocyte maturation, Acta Biomaterialia, Volume 197, 2025, Pages 135-151, ISSN 1742-7061,
https://doi.org/10.1016/j.actbio.2025.03.020.
-
Long-term HBV infection of engineered cultures of induced pluripotent stem cell-derived hepatocytes
Yuan Y, Bodke VV, Lin C, Gao S, Rehman J, Li J, Khetani SR. Long-term HBV infection of engineered cultures of induced pluripotent stem cell-derived hepatocytes. Hepatol Commun. 2024 Jul 31;8(8):e0506. doi: 10.1097/HC9.0000000000000506. PMID: 39082962.
-
Engineered cocultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation
Grace E. Brown et al. ,Engineered cocultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation. Sci. Adv. 10, eadg1222 (2024). DOI: 10.1126/sciadv.adg1222
-
Decellularized Liver Nanofibers Enhance and Stabilize the Long-Term Functions of Primary Human Hepatocytes In Vitro
Liu JS, Madruga LYC, Yuan Y, Kipper MJ, Khetani SR. Decellularized Liver Nanofibers Enhance and Stabilize the Long-Term Functions of Primary Human Hepatocytes In Vitro. Adv Healthc Mater. 2023 Jul;12(19):e2202302.
-
A human iPSC-derived hepatocyte screen identifies compounds that inhibit production of Apolipoprotein B.
Liu JT, Doueiry C, Jiang YL, Blaszkiewicz J, Lamprecht MP, Heslop JA, Peterson YK, Carten JD, Traktman P, Yuan Y, Khetani SR, Twal WO, Duncan SA. A human iPSC-derived hepatocyte screen identifies compounds that inhibit production of Apolipoprotein B. Commun Biol. 2023 Apr 24;6(1):452.
-
Engineered Platforms for Maturing Pluripotent Stem Cell-Derived Liver Cells for Disease Modeling
Yuan Y, Cotton K, Samarasekera D, Khetani SR. Engineered Platforms for Maturing Pluripotent Stem Cell-Derived Liver Cells for Disease Modeling. Cell Mol Gastroenterol Hepatol. 2023;15(5):1147-1160.
-
Atrial Fibrillation ModelList Item 1
Mature Patient Stem Cell-Derived Atrial Cardiomyocytes Unmask Ion Channel and Metabolic Defects in an NPPA Atrial Fibrillation Model. JCI Insight (2022)
-
See All MTM Lab Publications >>
