Preclinical compounds tested in animal models often demonstrate limited efficacy when transitioned into patients. As a result, individuals are assigned to treatment regimens that may be ineffective at treating their disease. The development of more clinically relevant models, such as patient-derived xenografts (PDXs), will (1) more completely mimic the human condition and (2) more accurately predict tumor responses to previously untested therapeutics.PDX models are clinically relevant as tumor tissue is implanted directly from human donor to the mouse recipient. Therefore, these models prevent cell population selection, intentional or unintentional, as the human tissue adapts to an in vitro, two-dimensional environment prior to implantation into a three-dimensional in vivo murine host. Often, cell heterogeneity and tumor architecture can be maintained from human to the PDX model in the mouse. This protocol describes the engraftment and propagation processes for establishing colorectal (CRC) PDX models in mice, using tumor tissue from human subjects.
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http://dx.doi.org/10.1007/978-1-4939-7765-9_20 | DOI Listing |
Stem Cell Reports
August 2024
Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lübeck, Germany; Cardiovascular Regeneration Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain. Electronic address:
Transplantation of pluripotent stem cell-derived cardiomyocytes is a novel promising cell-based therapeutic approach for patients with heart failure. However, engraftment arrhythmias are a predictable life-threatening complication and represent a major hurdle for clinical translation. Thus, we wanted to experimentally study whether impulse generation by transplanted cardiomyocytes can propagate to the host myocardium and overdrive the recipient rhythm.
View Article and Find Full Text PDFMicrobiome
July 2024
Section of Food Microbiology, Gut Health, and Fermentation, Department of Food Science, University of Copenhagen, Rolighedsvej 26 4, 1958, Frederiksberg, Denmark.
Background: Fecal microbiota transplantation (FMT) and fecal virome transplantation (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like donor variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) with FMT or FVT hinder their wider clinical application in treating less acute diseases.
View Article and Find Full Text PDFCell
June 2024
Institute for the Biology of Stem Cells, University of California, Santa Cruz, Santa Cruz, CA 95064, USA; Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA. Electronic address:
Platelet dysregulation is drastically increased with advanced age and contributes to making cardiovascular disorders the leading cause of death of elderly humans. Here, we reveal a direct differentiation pathway from hematopoietic stem cells into platelets that is progressively propagated upon aging. Remarkably, the aging-enriched platelet path is decoupled from all other hematopoietic lineages, including erythropoiesis, and operates as an additional layer in parallel with canonical platelet production.
View Article and Find Full Text PDFClin Transl Oncol
September 2024
The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Purpose: In the pursuit of creating personalized and more effective treatment strategies for lung cancer patients, Patient-Derived Xenografts (PDXs) have been introduced as preclinical platforms that can recapitulate the specific patient's tumor in an in vivo model. We investigated how well PDX models can preserve the tumor's clinical and molecular characteristics across different generations.
Methods: A Non-Small Cell Lung Cancer (NSCLC) PDX model was established in NSG-SGM3 mice and clinical and preclinical factors were assessed throughout subsequent passages.
Genetically diverse simian arteriviruses (simarteriviruses) naturally infect geographically and phylogenetically diverse monkeys, and cross-species transmission and emergence are of considerable concern. Characterization of most simarteriviruses beyond sequence analysis has not been possible because the viruses fail to propagate in the laboratory. We attempted to isolate 4 simarteriviruses, Kibale red colobus virus 1, Pebjah virus, simian hemorrhagic fever virus, and Southwest baboon virus 1, by inoculating an immortalized grivet cell line (known to replicate simian hemorrhagic fever virus), primary macaque cells, macrophages derived from macaque induced pluripotent stem cells, and mice engrafted with macaque CD34+-enriched hematopoietic stem cells.
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