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TOPICAL COLLECTIONS

Development of Stem-Cell-Derived Human Disease Models

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Guest Editors

Carla Frau

Carla Frau

Cancer Research Center of Lyon (CRCL) (France) and University of Pittsburgh – Liver Research Center (USA)

Dr. Carla Frau is a Research Scientist qualified in cancer and stem cell-derived disease modeling. With over ten years of experience in academia, she developed expertise in stem cell biology and building complex disease ex vivo tools, with devotion to the cutting-edge models of intestinal organoids, patient-derived pluripotent stem cells, and co-culture of different cells lineages. Carla Frau received her "Doctor of Pharmacy" degree from the University of Cagliari (Italy) in 2010 with a final score of 110/110 Summa cum Laude. She obtained her PhD in oncology and molecular pathology from the University of Cagliari in 2014. Her research project focused on the role of the nuclear thyroid hormone receptors (TRs) in hepatocellular carcinoma (HCC) development and liver regeneration. In 2015, she was awarded a postdoctoral fellowship by the French Association for Cancer Research (ARC). At the Cancer Research Center of Lyon (CRCL), she developed intestinal organoids (from transgenic mouse models and patients) to investigate the role of different intestinal stem cell populations in intestinal epithelial regeneration and resistance to chemotherapy. For her studies in 2018, she was awarded the Best Foreign Post-Doc Prize by the University of Lyon. She is particularly interested in developing ex vivo human models reproducing as closely as possible the reality of diseases, believing that this is the most effective way to advance the understanding of pathologies and the development of new drugs.

Nils Haep

Nils Haep

Experimental Surgery – Charité, Berlin (Germany)

Dr. Nils Haep is passionate about liver research and strives to understand genetic influences in non-alcoholic steatohepatitis. He is fascinated in using tissue engineering techniques to create novel disease models. Recently, he developed and patented a transcriptional gene therapy for liver failure, with the goal of helping patients with end-stage liver disease. Dr. Haep graduated from Heinrich-Heine-Universität Düsseldorf with a medical degree in 2015. Then, he started his training in General, Visceral, and Transplantation Surgery at Charité – Universitaetsmedizin Berlin's Department of General, Visceral, and Transplantation Surgery. In 2020, he successfully defended his doctoral thesis, "The EphB-recpetors and their function for the podocyte". Between 2019 and 2022, Dr. Haep completed postdoctoral training in the lab of Prof. Soto-Gutierrez at the University of Pittsburgh's Liver Research Center (USA).  

Collection Overview

Until 2015, the drug development process was marked by important failures, especially in phase II and III clinical trials. The main reason for this low success is related to a lack of reliable preclinical models capable of closely mimicking disease onset.

Cancers are incredibly complex and heterogeneous. Diseases have a multicellular composition and complex interactions.

The advent of in vitro / ex vivo stem-cell-derived disease models, such as human IPSCs, 3-D organoids, and co-culture of various cell types, has significantly accelerated scientific research and the drug discovery process.

Tumor organoids derived from patients exhibit a high degree of similarity to the original tumor composition and intratumor heterogeneity. Additionally, they are highly predictive of patients' chemotherapy responses. IPSC-derived disease models reproduce disease biology and functional interactions between various cell types.

However, establishing and expanding these assays can reveal technical difficulties. The isolation of primary cells from intact/fresh tissues with high quality and viability, IPSC reprogramming efficacy in generating fully differentiated and functional phenotypes, and the co-culture of multiple cell lineages with proper cell-cell interactions require precise handling and maintenance.

Overall, the potential of these models includes a large spectrum of applications, ranging from the prediction of drug response for personalized therapy to preclinical drug testing for ADME evaluation and organ-specific toxicity applications.

This method collection aims to provide a portfolio of detailed protocols to assist the scientific community in generating in vitro human models with the benefit of overcoming the most difficult steps of the procedures.

Articles

Isolation and Identification of Mesenchymal Stem Cells Derived from Adipose Tissue of Sprague Dawley Rats
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Isolation and Identification of Mesenchymal Stem Cells Derived from Adipose Tissue of Sprague Dawley Rats

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Cited by 3

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2023

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