Abstract
BackgroundEstablishment of transplantable tumors in clinically relevant large animals allows translational studies of novel cancer therapeutics.MethodsHere we describe the establishment, characterization, and serial transplantation of a naturally occurring B-cell lymphoma derived from a unique, highly inbred sub-line of Massachusetts General Hospital (MGH) major histocompatibility complex (MHC)-defined miniature swine.ResultsThe lymphoblastic cell line (LCL) originated from peripheral blood of a 2.5 year old female swine leukocyte antigen (SLA)dd-inbred miniature swine breeder demonstrating clinical signs of malignancy. Flow cytometric phenotypic analysis of subclones derived from the original cell line revealed surface markers commonly expressed in a B-cell lineage neoplasm. A subclone of the original LCL was transplanted into mildly-conditioned histocompatible miniature swine and immunocompromised NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. Tissue and blood samples harvested 2 weeks following subcutaneous and intravenous injection in a highly inbred SLAdd pig were cultured for tumor growth and phenotypic analysis before serial transfer into NSG mice. Evidence of tumor growth in vivo was found in all tumor cell recipients. In vitro growth characteristics and surface phenotype were comparable between the original and serially transplanted tumor cell lines.ConclusionsThese results indicate the feasibility of developing a large-animal transplantable tumor model using cells derived from spontaneously occurring hematologic malignancies within the highly inbred miniature swine herd.
Highlights
Establishment of transplantable tumors in clinically relevant large animals allows translational studies of novel cancer therapeutics
Characterization of spontaneous tumor cell lines Malignancy was suspected in a 2.5 year old female generation (G)11 inbred DD animal 21353, which presented with weight loss, mild head tilt, lethargy, and an elevated white blood cell count
Immunophenotyping by flow cytometry identified major histo‐ compatibility complex (MHC) class I expression as being comparable to normal whole blood lymphocyte population, while all cells stained positive for MHC class II, representing a homogenous population (Fig. 3a, b)
Summary
Establishment of transplantable tumors in clinically relevant large animals allows translational studies of novel cancer therapeutics. The MGH MHC-defined miniature swine herd is a unique research animal resource for the study of transplantation and tolerance induction [5]. These miniature swine develop malignancies under conditions. The inbred DD subline is not yet fully syngeneic, animals from the 7th generation of this line were shown to be histocompatible by accepting heart and reciprocal skin grafts without immunosuppressive intervention [9]. We describe the characterization of a spontaneous hematologic malignancy discovered in a naïve DD inbred miniature swine, as well as initial attempts at serial transplantation within this model
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
