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Establishment and Propagation of Human Retinoblastoma Tumors in Immune Deficient Mice
Published on: August 4, 2011
Looking for the Most Suitable Orthotopic Retinoblastoma Mouse Model in Order to Characterize the Tumoral Development
Stéphanie Lemaitre1, Florent Poyer2, Sergio Marco2
1Institut Curie, Research Center, PSL Research University, Chemistry, Modelisation and Imaging for Biology (CMIB), Centre Universitaire, Orsay, France 2INSERM U 1196, CNRS UMR 9187, Paris-Saclay University, Paris-Sud University, Centre Universitaire, Orsay, France 3Institut Curie, Hospital, Ophthalmology Department, Paris, France 4Sorbonne Paris Cité, Paris Descartes University, Paris, France.
Purpose:
Because retinoblastoma therapies have many adverse effects, new approaches must be developed and evaluated on animal models. We describe orthotopic xenograft models of retinoblastoma using different strains of mice, suitable for this purpose.
Methods:
Human retinoblastoma tumors were established on immunodeficient mice by subcutaneous engraftment of tumors from enucleated eyes. The orthotopic model was obtained by subretinal injections of suspension cells into the right eye of immunodeficient (Swiss-nude, severe combined immunodeficiency [SCID]) and immunocompetent mice (C57BL/6N, B6Albino). In vivo tumor growth was monitored by fundus and spectral-domain optical coherence tomography (SD-OCT) imaging and compared with histology.
Results:
Retinal and vitreal tumor growth was achieved both in immunocompetent and immunodeficient strains after the subretinal injection of tumor cells. The best tumor engraftment rate was obtained in the SCID mice (68.8%). No tumor growth was observed in the C57BL/6N strain. Chronic retinal detachment may occur in most strains after the subretinal injection, in particular the Swiss-nude strain, which exhibits retinal degeneration.
Conclusions:
The setting up of an orthotopic mouse model depends mainly on the choice of the engrafted cells (cell lines or patient-derived xenografts) but it can also depend on the xenografted mouse strain. Severe combined immunodeficiency mice (an immunodeficient strain) achieved the best tumor engraftment rate (68.8%). However, intraocular tumor growth was also satisfactory (50%) in the immunocompetent strain B6Albino, and this strain will allow to exploit the immune response after a tumor treatment. Both of these strains may therefore be recommended when setting up orthotopic retinoblastoma xenografts.
Insights
Developing new retinoblastoma treatments requires effective animal models. This study established orthotopic xenografts in mice, finding severe combined immunodeficiency (SCID) mice yielded the best tumor engraftment for retinoblastoma research.
Area of Science:
- Ophthalmology
- Oncology
- Animal Models
Background:
- Current retinoblastoma therapies have significant adverse effects.
- There is a need for novel therapeutic strategies and reliable animal models for evaluation.
Purpose of the Study:
- To develop and evaluate orthotopic xenograft models of retinoblastoma in different mouse strains.
- To establish suitable animal models for preclinical testing of new retinoblastoma therapies.
Main Methods:
- Human retinoblastoma tumors were engrafted into immunodeficient and immunocompetent mice.
- Orthotopic models were created via subretinal injections.
- Tumor growth was monitored using fundus imaging, spectral-domain optical coherence tomography (SD-OCT), and histology.
Main Results:
- Retinal and vitreal tumor growth was achieved in both immunocompetent and immunodeficient mice.
- Severe combined immunodeficiency (SCID) mice showed the highest tumor engraftment rate (68.8%).
- The B6Albino immunocompetent strain demonstrated satisfactory intraocular tumor growth (50%).
Conclusions:
- The choice of mouse strain is crucial for establishing orthotopic retinoblastoma xenografts.
- SCID mice are recommended for optimal tumor engraftment.
- The B6Albino strain is suitable for studies investigating the immune response to retinoblastoma treatments.

