Review
Engineering, Biomedical
Taiyu Song, Bin Kong, Rui Liu, Yuan Luo, Yongan Wang, Yuanjin Zhao
Summary: This work summarizes and analyzes the recent developments in engineering pancreatic tumor organoid models, and discusses the future direction of improving the organoid models for their application prospects in clinical treatment.
ADVANCED HEALTHCARE MATERIALS
(2023)
Review
Pharmacology & Pharmacy
Estrella Gonzales-Aloy, Aria Ahmed-Cox, Maria Tsoli, David S. Ziegler, Maria Kavallaris
Summary: Brain cancer is the most deadly cancer and the blood-brain barrier (BBB) poses a challenge for drug delivery. The BBB becomes disrupted in brain cancers, forming the blood-brain tumor barrier (BBTB). 3D cell models have the potential to serve as physiologically relevant in vitro models for studying the BBB and BBTB.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Article
Chemistry, Multidisciplinary
Yan Zhao, Zhi-Xuan Li, Yan-Jing Zhu, Jing Fu, Xiao-Fang Zhao, Ya-Ni Zhang, Shan Wang, Jian-Min Wu, Kai-Ting Wang, Rui Wu, Cheng-Jun Sui, Si-Yun Shen, Xuan Wu, Hong-Yang Wang, Dong Gao, Lei Chen
Summary: This study investigates the molecular heterogeneity and evolution of hepatobiliary tumors using single-cell RNA sequencing, revealing that certain tumor subpopulations exhibit broad-spectrum drug resistance. The CD44-positive population may play a key role in drug resistance. Shared metabolism advantage clusters across organoids and the combination of GAPDH and NDRG1 are proposed as independent predictors for patient survival.
Article
Oncology
Amani A. Gillette, Christopher P. Babiarz, Ava R. VanDommelen, Cheri A. Pasch, Linda Clipson, Kristina A. Matkowskyj, Dustin A. Deming, Melissa C. Skala
Summary: Gastroenteropancreatic neuroendocrine tumors (GEP-NET) make up around 60% of all neuroendocrine tumors, with low/intermediate grade human GEP-NETs having slow growth rates that traditional laboratory culture methods struggle to capture. The study explores the use of a label-free, non-destructive optical metabolic imaging (OMI) method to measure drug response in live GEP-NET patient-derived cancer organoids (PDCOs), showing promising results in testing drug combinations for GEP-NET treatment.
Article
Pharmacology & Pharmacy
Sanjay Kumar, Manita Raina, Kalpana Tankay, Gaurav Milind Ingle
Summary: Despite recent advances in cancer treatment, ovarian cancer patients continue to face challenges such as late-stage diagnosis, disease recurrence, and the lack of early biomarkers, resulting in a relatively low survival rate. The development of the patient-derived organoid model provides a unique platform for identifying tumor origin, drug screening, and precision medicine development, offering a promising approach in advancing ovarian cancer research. This review summarizes the progress in patient-derived organoids and their clinical relevance, highlighting their uses in transcriptomics, genomics profiling, drug screening, translational study, and their potential impact on precision medicine development in ovarian cancer.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Mirian Romitti, Adrien Tourneur, Barbara de Faria da Fonseca, Gilles Doumont, Pierre Gillotay, Xiao-Hui Liao, Sema Elif Eski, Gaetan Van Simaeys, Laura Chomette, Helene Lasolle, Olivier Monestier, Dominika Figini Kasprzyk, Vincent Detours, Sumeet Pal Singh, Serge Goldman, Samuel Refetoff, Sabine Costagliola
Summary: The study reports the generation of transplantable thyroid organoids derived from human embryonic stem cells, which can restore thyroid hormone levels in athyreotic mice. Thyroid hormones are essential for the normal functioning and growth of tissues, and hypothyroidism is a common disorder that is difficult to treat effectively. This research provides proof of concept for future therapeutic development.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Wei Zhang, Xiaoqiang Zheng
Summary: In addition to immune checkpoint inhibitors, self-assembly immunotherapy drugs have also been rapidly developed. Traditional tumor immunotherapy drugs are classified into five categories based on immune targets: immune checkpoint inhibitors, direct immune modulators, adoptive cell therapy, oncolytic viruses, and cancer vaccines. The emergence of self-assembled drugs with improved precision and environmental sensitivity offers a promising innovation approach. However, conventional evaluations using two-dimensional cell lines and animal models may be unsuitable for immunotherapy drugs, and patient-derived xenograft and organoid models better maintain tumor heterogeneity and immunity.
FRONTIERS IN ONCOLOGY
(2023)
Article
Genetics & Heredity
Sichong Peng, Rebecca Bellone, Jessica L. Petersen, Theodore S. Kalbfleisch, Carrie J. Finno
Summary: ATAC-seq is a popular method to assess genome-wide chromatin accessibility, and the extraction and storage of nuclei from horse tissues can impact the experimental results, with tissue type dictating the optimal approach for ATAC-seq experiments.
FRONTIERS IN GENETICS
(2021)
Review
Biotechnology & Applied Microbiology
Qian Yang, Mengmeng Li, Xinming Yang, Zian Xiao, Xinying Tong, Ayinuer Tuerdi, Shisheng Li, Lanjie Lei
Summary: Malignant tumors are a major cause of death worldwide, and developing research models that closely resemble original tumor characteristics is crucial for advancing our understanding of tumor development, improving drug safety and efficacy, and personalizing treatment plans. Organoids have emerged as a valuable tool in tumor research due to their ability to preserve the structure, heterogeneity, and cellular functions of original tumors. This review discusses the history and characteristics of tumor organoids and their combination with emerging technologies such as tissue-engineered cell scaffolds, microfluidic devices, 3D bioprinting, rotating wall vessels, and CRISPR-Cas9. It also summarizes the progress and applications of tumor organoid models in basic and clinical research, including studying tumor development mechanisms, drug development and screening, precision medicine, immunotherapy, and simulating the tumor microenvironment. The review concludes by addressing the current limitations of tumor organoids and potential future directions.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Review
Oncology
Hanxiao Xu, Dechao Jiao, Aiguo Liu, Kongming Wu
Summary: Cancer is a life-threatening disease with intratumor heterogeneity. Personalized tumor models capturing individual patients' tumor heterogeneity are urgently needed for precision medicine. Organoid technology, which can generate three-dimensional tissues that accurately recapitulate the characteristics of primary tumors, has shown great potential in accurately modeling cancer. Tumoroids serve as a valuable tool for the discovery of therapeutic targets, prediction of treatment response, and exploration of potential therapies.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Zhichao Li, Haibo Xu, Yanqing Gong, Wei Chen, Yonghao Zhan, Lei Yu, Yangyang Sun, Aolin Li, Shiming He, Bao Guan, Yucai Wu, Gengyan Xiong, Dong Fang, Yuhui He, Qi Tang, Lin Yao, Zheng Hu, Hongbing Mei, Zhisong He, Zhiming Cai, Yinglu Guo, Xuesong Li, Liqun Zhou, Weiren Huang
Summary: The study successfully generated a library of 25 patient-derived UTUC organoid lines using a modified organoid culture system, retaining similar histological architectures and gene expression profiles. The research demonstrates that this model can be used to identify responses of UTUC organoids to different anticancer drugs and supports exploration of novel treatment strategies.
Article
Chemistry, Multidisciplinary
Matthew J. Mosquera, Sungwoong Kim, Rohan Bareja, Zhou Fang, Shuangyi Cai, Heng Pan, Muhammad Asad, Maria Laura Martin, Michael Sigouros, Florencia M. Rowdo, Sarah Ackermann, Jared Capuano, Jacob Bernheim, Cynthia Cheung, Ashley Doane, Nicholas Brady, Richa Singh, David S. Rickman, Varun Prabhu, Joshua E. Allen, Loredana Puca, Ahmet F. Coskun, Mark A. Rubin, Himisha Beltran, Juan Miguel Mosquera, Olivier Elemento, Ankur Singh
Summary: This study defined the role of ECM signals in the development of CRPC-NEPC and identified potential therapeutic targets for neuroendocrine prostate cancer. In animal models, strong anti-tumor responses were observed with the use of a DRD2 inhibitor, and a combination of epigenetic inhibitors and DRD2 treatment was shown to overcome therapeutic resistance in CRPC-NEPC under drug-resistant ECM conditions.
ADVANCED MATERIALS
(2022)
Review
Oncology
Yanyun Gao, Marianna Kruithof-de Julio, Ren-Wang Peng, Patrick Dorn
Summary: Malignant pleural mesothelioma is a deadly cancer with limited treatment options and low survival rates. Patient-derived organoid cultures offer a promising approach for studying the disease, identifying new therapeutic targets, and developing personalized treatments.
Article
Engineering, Biomedical
Guocheng Fang, Hongxu Lu, Russul Al-Nakashli, Robert Chapman, Yingqi Zhang, Lining Arnold Ju, Gungun Lin, Martina H. Stenzel, Dayong Jin
Summary: This study presents a method to model peristalsis in human colon tumor organoids on a microfluidic chip. The chip allows the control of peristalsis amplitude and rhythm, and enables high throughput culture of organoids. Results show the importance of mimicking mechanical stimuli in the physiological environment when evaluating nanoparticles in vitro.
Article
Oncology
Elham Aida Farshadi, Jiang Chang, Bharath Sampadi, Michail Doukas, Freek Van 't Land, Fleur van der Sijde, Eveline E. Vietsch, Joris Pothof, Bas Groot Koerkamp, Casper H. J. van Eijck
Summary: This study investigated the sensitivity and resistance of cancer cells to therapy by generating organoids from resected tumors of patients who received neoadjuvant FOLFIRINOX chemotherapy. The results demonstrated that neoadjuvant FOLFIRINOX-treated organoids displayed resistance to FOLFIRINOX, irinotecan, and oxaliplatin, suggesting that continuing FOLFIRINOX therapy may not be advantageous for these patients. Gene-expression profiles of PDAC organoids identified targetable pathways involved in chemoresistance development, indicating potential for combination therapy strategies.
CLINICAL CANCER RESEARCH
(2021)
Article
Biochemical Research Methods
Tiffany M. Heaster, Alex J. Walsh, Yue Zhao, Scott W. Hiebert, Melissa C. Skala
JOURNAL OF BIOPHOTONICS
(2018)
Article
Biochemical Research Methods
Zijie J. Wang, Alex J. Walsh, Melissa C. Skala, Anthony Gitter
JOURNAL OF BIOPHOTONICS
(2020)
Article
Engineering, Biomedical
Alex J. Walsh, Katherine P. Mueller, Kelsey Tweed, Isabel Jones, Christine M. Walsh, Nicole J. Piscopo, Natalie M. Niemi, David J. Pagliarini, Krishanu Saha, Melissa C. Skala
Summary: Autofluorescence lifetime imaging can be used to classify T cells accurately based on their activation state and further identify their subtypes. This non-destructive method determines T cell function effectively.
NATURE BIOMEDICAL ENGINEERING
(2021)
Article
Biochemical Research Methods
Linghao Hu, Nianchao Wang, Elizabeth Cardona, Alex J. Walsh
BIOMEDICAL OPTICS EXPRESS
(2020)
Article
Microbiology
Woojong Lee, Brock Kingstad-Bakke, Brett Paulson, Autumn Larsen, Katherine Overmyer, Chandranaik B. Marinaik, Kelly Dulli, Randall Toy, Gabriela Vogel, Katherine P. Mueller, Kelsey Tweed, Alex J. Walsh, Jason Russell, Krishanu Saha, Leticia Reyes, Melissa C. Skala, John-Demian Sauer, Dmitry M. Shayakhmetov, Joshua Coon, Krishnendu Roy, M. Suresh
Summary: The study identified an adjuvant called Adjuplex that can safely induce potent T cell immunity and protect against virus and intracellular bacterial infections through unique mechanisms. This finding challenges the current metabolic paradigm by showing that effective dendritic cell cross-presentation and T cell activation can occur without reliance on glycolysis, providing insights for the development of new adjuvants for T cell-mediated protection against infections.
Article
Biochemical Research Methods
Rebecca Schmitz, Kelsey Tweed, Christine Walsh, Alex J. Walsh, Melissa C. Skala
Summary: The study investigated the effect of extracellular pH on the fluorescence lifetimes of FAD, FMN, and NAD(P)H. Results showed that FAD and NAD(P)H mean lifetimes increased and decreased, respectively, with increasing pH, with differences observed between the two cell lines.
JOURNAL OF BIOMEDICAL OPTICS
(2021)
Article
Biochemical Research Methods
Elizabeth N. Cardona, Alex J. Walsh
Summary: Drug-resistant cells and anti-inflammatory immune cells contribute to tumor aggression and worse patient outcomes. Single cell analysis of autofluorescence images provides a live-cell assay to quantify cellular heterogeneity. In this study, Gaussian distribution modeling and machine learning classification were used to identify rare cells within simulated autofluorescence lifetime image data.
Article
Biology
Veronika Miskolci, Kelsey E. Tweed, Michael R. Lasarev, Emily C. Britt, Alex J. Walsh, Landon J. Zimmerman, Courtney E. McDougal, Mark R. Cronan, Jing Fan, John-Demian Sauer, Melissa C. Skala, Anna Huttenlocher
Summary: This study used two-photon imaging of autofluorescent metabolic coenzymes NAD(P)H and FAD to assess macrophage metabolism in the wound microenvironment. Results showed that inhibiting glycolysis led to a more oxidized intracellular redox state in macrophages, and infection and thermal injury induced a more oxidized redox state in wounded tissues. Kinetic analysis revealed a shift toward a more reduced redox state during tissue repair. Metformin improved tissue repair by reducing TNF alpha+ wound macrophages and making the intracellular redox state more reduced, while depletion of STAT6 impaired regeneration by increasing TNF alpha+ wound macrophages and making the redox state more oxidized. The study suggests that autofluorescence of NAD(P)H and FAD can be used to probe the temporal and spatial regulation of macrophage metabolism during tissue damage and repair.
Article
Multidisciplinary Sciences
Anna Theodossiou, Linghao Hu, Nianchao Wang, Uyen Nguyen, Alex J. Walsh
Summary: Cellular metabolism is the process by which cells generate energy, and can be studied using autofluorescence imaging techniques such as FLIM to quantify the fluorescence intensity and lifetimes of coenzymes NAD(P)H and FAD.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Oncology
Wangie Yu, Yunyun Chen, Nagireddy Putluri, Abdullah Osman, Cristian Coarfa, Vasanta Putluri, Abu H. M. Kamal, Jennifer Kay Asmussen, Panagiotis Katsonis, Jeffrey N. Myers, Stephen Y. Lai, Wuhao Lu, Clifford C. Stephan, Reid T. Powell, Faye M. Johnson, Heath D. Skinner, Jawad Kazi, Kazi Mokim Ahmed, Linghao Hu, Addison Threet, Matthew D. Meyer, James A. Bankson, Tony Wang, Jack Davis, Kirby R. Parker, Madison A. Harris, Mokryun L. Baek, Gloria V. Echeverria, Xiaoli Qi, Jin Wang, Andy I. Frederick, Alex J. Walsh, Olivier Lichtarge, Mitchell J. Frederick, Vlad C. Sandulache
Summary: We found that head and neck squamous cell carcinoma cells acquire cisplatin resistance through metabolic rewiring, including reduced KEAP1 gene activity, activation of the Nrf2 pathway, increased cell biomass and reducing equivalents, and enhanced glucose and glutamine metabolism. These metabolic changes result in reduced energy production and proliferation, leading to resistance to cisplatin.
BRITISH JOURNAL OF CANCER
(2023)
Article
Multidisciplinary Sciences
Oscar Benavides, Holly A. Gibbs, Berkley J. White, Roland C. Kaunas, Carl Gregory, Alex Walsh, Kristen Maitland
Summary: The adoption of cell-based therapies into the clinic will require large-scale expansion, best suited by bioreactor-microcarrier cultures. However, the use of spherical microcarriers hinders the in-process visualization and monitoring of cell characteristics. This study developed a robust optical imaging and image-analysis assay to non-destructively quantify cell number and volume, motivating the advancement of on-line optical monitoring systems.
Article
Multidisciplinary Sciences
Nianchao Wang, Linghao Hu, Alex J. Walsh
Summary: Many techniques and software packages have been developed to segment individual cells within microscopy images, necessitating a robust method to evaluate images segmented into a large number of unique objects. Currently, segmented images are often compared with ground-truth images at a pixel level; however, this standard pixel-level approach fails to compute errors due to pixels incorrectly assigned to adjacent objects. The proposed per-object segmentation evaluation algorithm (POSEA) provides accurate evaluation metrics for objects with pixels incorrectly assigned to adjacent objects and is robust for use across a variety of applications that require evaluation of the segmentation of unique adjacent objects.
Article
Engineering, Biomedical
Linghao Hu, Samantha Morganti, Uyen Nguyen, Oscar R. Benavides, Alex J. Walsh
Summary: Cell-based therapies require non-destructive methods for assessment to ensure viability and uncontaminated therapies for patients. Label-free nonlinear optical imaging techniques, such as second-harmonic generation for collagen and autofluorescence microscopy for cellular metabolism, provide valuable information for assessing cell-based therapies. This review discusses the applications and potential of label-free imaging technologies for quality control and outlines current limitations and future directions.
CURRENT OPINION IN BIOMEDICAL ENGINEERING
(2023)
Article
Chemistry, Physical
Sabrina N. VandenHeuvel, Heather A. Farris, Dillon A. Noltensmeyer, Sanjana Roy, Del A. Donehoo, Scott Kopetz, Svasti Haricharan, Alex J. Walsh, Shreya Raghavan
Summary: Metastatic cancers are resistant to chemotherapy and require biomimetic 3D in vitro models to study their mechanisms. This study successfully engineered reproducible and quantifiable 3D models to recapitulate the complex cascade of cancer cell invasion and colonization in distant organs. Through these models, it was found that the cancer cells exhibited metastatic properties and chemotherapy resistance. This research is important for identifying therapeutic targets to treat metastatic cancers.
Letter
Gastroenterology & Hepatology
Qin Zhang, Dennis K. Jeppesen, James N. Higginbotham, Michelle Demory Beckler, Emily J. Poulin, Alex J. Walsh, Melissa C. Skala, Eliot T. McKinley, H. Charles Manning, Matthew R. Hight, Michael L. Schulte, Kimberly R. Watt, G. Daniel Ayers, Melissa M. Wolf, Gabriela Andrejeva, Jeffrey C. Rathmell, Jeffrey L. Franklin, Robert J. Coffey
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2018)