Organoids are complex models that better summarize human diseases than cell Despite the simplicity and cost-efficiency of in vitro studies, these models lack the immune system, the microenvironment, and are not representative of tumor heterogeneity. Since in vivo models can overcome the limitations of metastasis studies and allow to exploration of the complex crosstalk involved in metastasis and stages, they are key to investigating alternative and innovative therapeutic approaches. Alfa Cytology is a leading global life sciences company. We have years of experience in constructing models for pancreatic cancer (PC), including PC cell models, PC organoids, genetically engineered mouse models, and transplantation models. We are now proud to offer genetically engineered mouse models for PC research. As one of the important in vivo models, genetically engineered mouse models not only inspire the biology of PC and highlight the importance of tumor stroma, but also have the ability to elucidate potential therapeutic and diagnostic targets.
Overview of PC genetically engineered mouse models (GEMMs)
Genetically engineered mouse models (GEMMs) transfer specific genes into mice via retrovirus by virtue of transgenic, knockout, and knock-in technologies. PC genetically engineered mice are designed by inducing specific mutations in pancreatic ductal adenocarcinoma (PDAC) -associated oncogenes and/or tumor suppressor genes in the mouse genome. Transgenic mice overexpressing Kras mutant genes can mimic pancreatic tumorigenesis, most PC GEMMs currently in use are developed using the Kras proto-oncogene. To date, several GEMMs are able to faithfully reproduce the genetic, molecular, histological and clinical characteristics of human PC, including KC, KPC, KD, and KPCZ models. Among them, the KPC model containing mutations in KRAS and TP53 (both driven by the pdx1-Cre transgene), is the most well-studied one. In the KPC model, similar to human PDAC, tumors develop spontaneously with dense connective tissue and a poor vascular system, thus maintaining the dynamics of the tumor microenvironment.
The services offering at Alfa Cytology
Preclinical tumor studies are designed to mimic human disease in an animal setting, and the biggest challenge for researchers is the translatability of the results. The ideal preclinical tumor model requires not only a specific tumor subtype but also mimics the complex microenvironment required for tumorigenesis. As a result, the modeling time is difficult to control, time-consuming and costly. To meet experimental requirements in terms of quantity and quality, Alfa Cytology has launched a systematic animal model transgenic platform for PC research. Our platform is based on a series of technologies, such as conditional gene knockout technology and CRISPR-Cas9 technology.
- Conditional gene knockout technology
This method can restrict gene modifications to a certain part or a certain developmental stage to enable precise control of the timing and space of mutated genes, thus allowing a more accurate study of gene function. We apply the most commonly used conditional gene knockout strategies, including the Cre/loxp recombinase and tet-on systems.
- CRISPR-Cas9 technology
CRISPR-Cas9 technology allows for more precise genome editing. Using this method, we can generate syngeneic mouse models that recapitulate human PC features.
Applications of our PC GEMMs
- Study the interactions between tumor and stromal cells, promoting the understanding of PC pathogenesis
- Study the disease progression from early stages of PanIN to primary and metastatic tumors
- Study the immune response in PC and test new immune-therapies
- Study the impact of microbiota composition and its effect on PC tumor development and patient survival
PC GEMMs are similar in nature to human disease, and in particular, their metastatic pattern is most similar to that of human PC. These models can be applied to investigate early-stage PC tumor formation, allowing researchers to determine PC pathogenesis and treatment efficacy. We can provide a variety of effective and customized PC transgenic models for testing the effectiveness of drugs according to the specific needs of our clients. If you are interested in our services, please contact us for a professional, competitively priced solution that fits your needs.
References
- Kong, Kaiwen, et al. "Progress in animal models of pancreatic ductal adenocarcinoma." Journal of Cancer 11.6 (2020): 1555.
- Miquel, Maria, Shuman Zhang, and Christian Pilarsky. "Pre-clinical Models of Metastasis in Pancreatic Cancer." Frontiers in cell and developmental biology (2021): 2825.