Article at Biocompare
:In Vivo Xenograft Services from Altogen Labs
What is Xenograft?
Xenotransplantation is a transfer of living cells of human origin to mouse, these cells are called xenografts or xenotransplants. This technology provides opportunity to develop treatment for such diseases as organ failure, cancer, Parkinson’s disease, diabetes and liver failure. The development of future drugs often depends on pre-clinical studies that use in vivo xenograft services.
Investigations into animal organ donor xenotransplantation suggest that although such nonhuman primates as baboons and chimpanzees may be closely related to humans they may not be the best candidates for organ donors as disease transmission, immune response, and extinction problems are of high risk. Other studies pinpoint baboons could be good models for drug development but due to cost efficiency, accessibility and being genetically well-characterized, mice or rats are typically used as human disease models. Immunocompromised mice models are routinely used in angiogenic studies, cancer studies, pharmacokinetic (PK) and pharmacodynamics (PD) studies.Altogen Labs
offers in vivo xenograft model services to conduct drug development for oncology, inflammation, diabetes, infectious diseases, obesity, immunology and pain research. Animal handling and maintenance is IACUC-regulated and GLP-compliant. We provide detailed experiment procedures, health reports and experimental data. Additional experimental services include tissue collection, histology, RNA isolation and gene expression analysis.
Xenograft Services and Disease Models
Xenograft disease animal models remain an important research tool, playing a major role in drug development and cancer research. The future of anti-tumor drug development depends on the testing of in vivo xenograft models to determine the inhibition of tumor growth, drug efficacy in order to understand the implications of the agents of interest and to design future combination studies. Xenograft in vivo services are used to measure the activity of anti-tumor medicines (compounds, proteins, vaccines) and screen for potential anti-cancer drugs based on the rate of engrafted tumor growth.
At Altogen Labs xenotransplantation process involves administration of selected tumorigenic cell line (usually of human origin) via subcutaneous injection. Alternative approaches include orthotopic, intramuscular, intravenous, intratracheal, or intraperitoneal administration. To enable in vivo imaging experiments researchers often use cell lines that express fluorescent proteins, such as RFP or YFP.
Xenograft procedures simulate biological activity observed in humans by the grafting of “foreign” tissue from one species to another. In most cases, human tumorigenic cells are introduced subcutaneously into immunodeficient nude mice to prevent rejection of the foreign cells by the mouse immune system. Some xenograft models use syngeneic models with intact immune systems to track the tumor growth with or without the compound of interest. The tumor size is measured throughout the study and tissue samples are preserved.
Once tumorigenic cells have been introduced into the xenograft model, a tumor is established and these mice can be used as a test subject for testing potential cancer therapies. Xenograft models of various tumor lines can sometimes prove to be difficult due to tumor take rates and significant variations in tumor size within a given xenograft tumor group.
Basic Study Design
Tumors are established in a group of 6- to 8-week-old BALB/c athymic (nude) mice, or 9-12 week old NOD/SCID immunocompromised mice by subcutaneous injection of tumor cell line cells (typically 1,000,000 cells per animal). The dosing of compounds is initiated when the mean tumor size reaches 50-100 mm3.
Administration options include the dosing route (intratumoral, intramuscular, oral, intravenous, intratracheal, subcutaneous, or intraperitoneal), dosing frequency (f.e. once or twice a day), and dosing duration. Negative control (1xPBS), and positive controls groups (such as cyclophosphamide 50 mg/kg) should be included in experimental design.
Mice are checked daily for clinical signs and tumor appearance. When tumors are measurable, animals are grouped based on tumor volume. Mice are dosed once or twice a day for 28 days via one route of administration (choice of oral, intratumoral, intraperitoneal, intratracheal, intramuscular, or subcutaneous). Blood sera can be collected at termination, and tumors and other major tissues can be collected and preserved if required.
Some of the tumorigenic cell lines maintained at Altogen Labs - LIST
Throughout the study, mice weight and tumor volume are measured via digital caliper readings on a scheduled basis. Once a predetermined endpoint has been reached, the tumors are harvested, serum is collected and tissue, organs, and/or tumors are preserved as requested. Complete profiling of agents and evaluation of drug treatments are provided. Data on angiogenesis, tumor growth, metastasis, and gene expression histopathology as well as measurements of bone destruction, tumor weight and cytokine and hormone induction are also collected.
Results and Analysis
Upon completion of the study, data is compiled, analyzed and summarized. The following information is included in Altogen Labs summary data report
Tumor and mouse caliper weight at endpoint
Approximate tumor volume (L x W2 /2)
Average time to predetermined endpoint
Histology analysis results
Life span (increased / decreased)
Tumor growth rate and tumor growth inhibition