for a 200 g rat, tumor volume cannot exceed 20,000 mm3). VCaP tumors grown in SCID/NCr mice or SRG rats were collected, fixed in 10% neutral buffered formalin, processed, paraffin embedded, sectioned, and stained for AR (ab108341, abcam) or PSA (A056201-2, Dako). Tissues were stained with H&E, P40, and TTF1. The wild-type Sprague Dawley rat thymus was comprised mostly of CD4/CD8 double positive cells whereas in the SRG rat, the viable cells recovered were CD4-/CD8- (Fig 1A–1C). The SRG rat spleen also has lower NK cells compared to the wild-type rat spleen (6.11%± 1.98 vs. 1.31% ± 1.31, respectively; Fig 1G–1I). In addition, SRG rats can also greatly reduce the time needed to establish a PDX bank and can produce sufficient tumor tissue in the first in vivo generation (P1) to make a full preclinical study possible in the subsequent passage (P2). Molecular characterization and histological analyses were performed for three PDX lines and showed high concordance between passages 1, 2 and 3 (P1, P2, P3), and the original patient sample. Low engraftment rates and slow growth for certain cancers like human non-small cell lung cancer (NSCLC) make it challenging to create these PDX models [8–10]. Individual level tumor measurements and body-weight data for all xenografts are provided in the supplemental tables. Its main advantage is its calmness and ease of handling. K) Quantification of data, n = 3, error ± SD. In rats, this is accomplished through inbreeding. Conceptualization, Discover a faster, simpler path to publishing in a high-quality journal. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, United States of America, Blood was collected in K2EDTA tubes. For all staining, tissue slides were incubated with primary antibody overnight at 4°C. NK cells in the SRG rat spleen (H) are similar to or less than the amount of NK cells in the wild-type rat. Yes Excluded Flora and Restricted Flora™ SD rats are useful as health sentinels, clean fosters or where co-housed with immunodeficient/genetically modified models. We next determined if SRG rats support the growth of human cancer cell lines that are difficult to grow in immunodeficient mouse strains. Thirty four SRG rats were used for PDX establishment studies and thirty four SRG rats were engrafted with commercially available cell lines for xenograft development. Our data demonstrate that the SRG rat has the potential to be a valuable model for evaluating drug efficacy in a wide range of human cancers. The SRG rat supports the growth of multiple human cancer cell lines, including lines that do not engraft or grow well in existing mouse models, such as VCaP. In order to evaluate the genomic instability of the PDX model, we performed next-generation sequencing after passages 1, 2 and 3 in SRG rats using a panel of 6000 genes, which are associated with a variety of cancers, for three of the seven PDX lines created (Table 2). For many human cancer cell lines, SRG rats display 80–100% engraftment and low variability in tumor growth leading to a high rate of enrollment into treatment studies allowing for a more defined and shorter enrollment window with fewer animals inoculated. In addition, animal technicians complete one-on-one hands-on training workshops to become adept at tumor measurements and monitoring, as well as monitoring clinical signs during daily health checks. Hence, this study aimed to investigate the anti-obesity activity of Elateriospermum tapos (E. tapos) shell extract in obesity induced Sprague Dawley rats. Body condition score was also assessed for mice and rats as previously described [17, 18]. Hesperidin a flavanoglycone protects against gamma-irradiation induced hepatocellular damage and oxidative stress in Sprague-Dawley rats. A549 (ATCC® CCL-185™), PC3 (ATCC® CRL-1435™), and LNCaP/AR were used as positive and negative controls. The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical and nutritional research. All other mouse studies were performed in the NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ, strain 005557 from The Jackson laboratory). Subsequent passages from mouse/rat to mouse/rat are annotated as PDX passage 2, 3 or P2, P3, etc, to establish a bank of tissues. We injected 2 x106 HCT-116 cells in Cultrex, an extracellular matrix protein isolated from Engelbreth-Holm-Swarm mouse sarcoma similar to Matrigel, into NSG mice and SRG rats. A : schematic representation of our exposure paradigm. "Rats, Sprague-Dawley" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings).Descriptors are arranged in a hierarchical structure, which enables searching at various levels of specificity. This in turn results in PDXs that no longer faithfully reflect the genomic landscape of the primary tumors. Overall, SRG rats demonstrated favorable take rate and growth kinetics for downstream efficacy studies. The caveat to using the rat for efficacy studies is the need for larger amounts of dosing materials. G-I) NK cells in G) wild-type rat spleen and H) SRG rat spleen. This work presents an experimental study with the intervention of GM rice feeding by Sprague Dawley rats. Compared to mice, rats are bigger, generally more aggressive, and more resistant to various ailments. Compared to NK cells in the wild-type rat (I; 10.1% CD161a+), the SRG rat has significantly reduced circulating NK cells (J; 0.5% CD161a+). The rationale for using this compound instead of the more active O6-benzylguanine and its substituted benzyl derivatives at the benzyl ring is its greater solubility in … In 1991, 8 colonies were selected to form the IGS Foundation Colony. Sprague Dawley rat: The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical and nutritional research. Furthermore, the rat can humanely support the growth of tumors that are 10 times the size of those in the mouse, which allows for more tissue at study completion for downstream analyses. Methods: Male Sprague Dawley rats were studied with either 20% fructose or 20% glucose in the drinking water and normal salt (0.4%) or high salt (4%) in the chow resulting in four dietary groups: fructose normal Fru+NS or high salt (Fru+HS) or glucose with normal (Glu+NS) or high salt (Glu+HS). Tumors were monitored once daily for signs of ulceration. Cells were stained with fluorophore-labeled antibodies at a final concentration of 25 μg/mL in 20 μL volume for 20 minutes. Immunodeficient mice have proven essential for the establishment of in vivo human tumor models. The processed soybean meal was added to formulated rodent diets at 20% (w/w) and fed to rats for 90 days. Data were collected from 40 Wistar-Kyoto (WKY) and 40 Sprague Dawley (SD) rats during an active escape-avoidance experiment. If avoidance did not occur, a series of footshocks was administered, and the rat could press a lever to escape (terminate shocks). T cells are significantly reduced in peripheral blood of the SRG rat (B; 1.6% CD4+, 5.3% CD8+, 1.2% CD4+/CD8+) compared to wild-type rat (A; 37.4% CD4+, 36.6% CD8+, 3.5% CD4+/CD8+). (Unpaired t-test, p-values: ** < 0.01). For example, efficacy, pharmacokinetics, clinical pathology, toxicity endpoints, systemic exposure, and biomarker endpoints can all be collected from one animal at several timepoints. Yes *indicates the intervals where L/M ratios of Fischer and Sprague-Dawley rats were significantly lower than the DI control. https://doi.org/10.1371/journal.pone.0240169.g002. CropLife International fully acknowledges the source and authors of the publication as detailed above. Overall, 20 male and 20 female SD rats were fed by pellets made by GM rice in 50% of needed carbohydrate for 90 days. SCID/NCr mice and SRG rats were inoculated with 5x106 and 10x106 VCaP cells, respectively, subcutaneously in the hind flank. De-identified patient samples were provided to Hera Biolabs in DMEM + 10% FBS, 1% Penicillin/Streptomycin, 1% Amphotericin B. The hairless mutation appeared in a SPRAGUE DAWLEY® colony in 2004; Bazzi et al. Tumor diameter was measured using digital calipers 3 times a week. The chart below indicates specific parameters that are monitored (Table 1). Hera BioLabs Inc., Lexington, Kentucky, United States of America, Spleen and thymus were collected in FACS buffer (BD Pharmingen 554656). The VCaP prostate cancer model is one such cell line that engrafts unreliably and grows irregularly in existing models but displays over 90% engraftment rate in the SRG rat with uniform growth kinetics. In the current exploration, different parts of bitter gourd were evaluated for their cholesterol lowering potential in cholesterol fed Sprague dawley rats. One such cell line is VCaP, a human prostate cancer cell line derived from a vertebral metastatic growth. Department of Human Genetics, The University of Michigan, Ann Arbor, Michigan, United States of America, The rat is the most commonly used rodent species for toxicology studies. We inoculated VCaP cells in Cultrex into the flanks of SCID/NCr mice, 5 x 106 cells (~70,000 cells/cm2 BSA), in keeping with published parameters. Serum was analyzed for PSA by ELISA (ALPCO #25-PSAHU-E01) according to manufacturer’s instructions. Epub 2013 Apr 22. CD® (Sprague Dawley) IGS Rat Details. Since recent studies have shown that with each successive passage in vivo, tumors become more divergent genetically from the parent tumor, shortening the number of passages required to conduct an efficacy study will reduce animal numbers, associated costs, and ensure the tumors are more closely related to the parent tumor to better predict drug outcomes . Hera Biolabs, Inc. provided support in the form of salaries for authors (FKN, BTA, SM, CM, JC, TYJ) and Poseida Therapeutics, Inc. provided support in the form of salaries for authors (EO, MT), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. All of the pathogenic SNPs identified in our analysis were conserved across all passages. Competing interests: Dr. Goutham Narla is on the scientific advisory board for HERA Biolabs. A substantial quantity of data on Sprague-Dawley (SD) and Hannover Wistar rats strains have been published concerning their source, diet, and housing conditions, as well as the incidences of nonneoplastic lesions and neoplasms observed in different laboratories. No, Is the Subject Area "Colorectal cancer" applicable to this article? Oral Administration of Aloe vera Ameliorates Wound Healing through Improved Angiogenesis and chemotaxis in Sprague Dawley Rats (E-pub Ahead of Print) To Charles River in 1950 from Sprague Dawley, Inc. No, Is the Subject Area "NK cells" applicable to this article? SCID/NCr mouse and SRG rat tumors expressed prostate-specific protein markers AR PSA (Fig 4E). Strikingly, circulating NK cells in the peripheral blood of the SRG rat are significantly reduced (0.5%) relative to wild-type levels (10.1%) (Fig 2I–2K). For this, we evaluated the phototoxicity using Sprague-Dawley (SD) rats for transdermal administered drugs and we studied the appropriate UVA dose using 8-methoxypsalen, which is a well-known phototoxic drug. Download. These primary patient tumor tissues, annotated as passage 1 or P1, were sectioned into 2mm x 2mm pieces and implanted subcutaneously on the flank of SRG rats or NSG mice using a 10G trocar. METHODS: Three groups of male Sprague Dawley rats (n=7) were fed either a control diet, based on AIN recommendations (53% cornstarch, 10% sucrose and 7% soybean oil), a high fat diet (25% soybean oil, 35% cornstarch) or a high fructose diet (53% fructose, 10% sucrose) for a 3 month period. D) Tumor growth curve in SRG rats inoculated with 10 x106 786-O cells. We have created the immunodeficient SRG rat, a Sprague-Dawley Rag2/Il2rg double knockout that lacks mature B cells, T cells, and circulating NK cells. Published success rates for NSCLC-PDX establishment subcutaneously in mouse models are in the range of 20–40% which means even at best, the models fail for more than half of the patients [8–10]. The average litter size of the Sprague Dawley rat is 10.5. These include cell lines that have poor take rates or variable growth kinetics in mice. Funding: NCI contract HHSN261201700017C supported PDX establishment and their molecular and histological characterizations, along with their drug response studies. This breed of rat was first produced by the Sprague Dawley farms (later to become the Sprague Dawley … Goat anti-mouse IgG-HRP conjugate antibody (PI31430, ThermoFisher Scientific) or Goat anti-rabbit IgG-HRP conjugate antibody (31460, ThermoFisher Scientific) were used as secondary antibodies. Yes By having this kind of population, it is possible to conduct experiments on the roles of genes, or conduct experiments that exclude variations in genetics as a factor. To detect T, B, and NK cells in SRG rats, flow cytometric analysis was performed on splenocyte, thymocytes, and whole peripheral blood using a BD LSRII. All the cells were grown in a humidified incubator at 37°C with 5% CO2. SD rats are docile and are easy to handle. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Patient derived lung tumor was implanted into SRG rats. For the purpose, four types of bitter gourd part i. e. whole fruit, seedless fruit, seeds, and seed extracts were used and compared with placebo in hypercholesterolemic rats. Cells were resuspended in 250 μL of each cell line’s respective culture media as listed in the Cell Culture methods. "Rats, Sprague-Dawley" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings).Descriptors are arranged in a hierarchical structure, which enables searching at various levels of specificity. Rats also accommodate serial blood and tumor tissue sampling for temporal assessment of several parameters from the same animal. Then, sampling was done from rats … Ns for Sprague-Dawley rats, respectively, were 5, 8, 10, 6, 9, 5, 14 and 6. Writing – original draft. Formal analysis, Knowing this cell line engrafts and grows poorly in the mouse and taking advantage of the size of the rat, we inoculated SRG rats with 10 x 106 cells (~40,000 cells/cm2 BSA). Jaya Sangodkar, Roles https://doi.org/10.1371/journal.pone.0240169.g005. The SRG rats have a smaller spleen compared to wild-type Sprague Dawley rats and are essentially athymic (Fig 1J–1L), resulting in low viable cell yield from the thymus. (Unpaired t-test, p-values: * < 0.05). Excellent reproductive performance and maternal characteristics. Yes We found that a UVA dose of 15 J/cm 2 was dose and … In comparison, mouse models may require multiple passages past the third or fourth before sufficient tumor-bearing animal numbers are produced for an efficacy study, increasing the risk of genetic drift from the original tumor. VCaP and MIA-PaCa-2 cells were grown in Advanced DMEM (ThermoFisher #11995065) with 10% fetal bovine serum (Atlanta Biologicals # S12450) and 1% penicillin and streptomycin solutions (Cat# 15140–122, ThemoFisher). Affiliations Studies were conducted after Institutional Animal Care and Use Committee approval and in strict compliance with institutional regulatory standards and guidelines. Sprague-Dawley rats (male 250–350 g, Taconic Farms) are anesthetized with chloral hydrate (400 mg/kg, i.p.) C) Tumor growth curve in SRG rats inoculated with 5 x106 HCC1954 cells. Rederived into an isolator foundation colony in 1997. studied the development of the hair follicle in individuals that displayed the hairless phenotype. Other criteria warranting euthanasia are ulceration on greater than 25% of the surface or perforation in any size ulceration that causes exudate or infection. A : Relative retroperitoneal fat weight. A) Tumor growth curve in NSG mice and SRG rats inoculated with 2x106 HCT-116 cells subcutaneously in the hind flank. A hot aqueous Our studies have demonstrated that SRG rats support growth of a wide array of human cancer cell lines, including ones that have poor uptake or variable growth kinetics in available mouse models. The lack of thymus tissue in the SRG rat results in a low recovery of viable thymocytes. The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical research.
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