Development of a Bioluminescent Human Osteosarcoma Model in Humanized NSG Mice: A Pilot Study
Yunmi Ko1,2, Yeon Ho Jeong2, Jin-Hee Seo3
1Department of Pediatrics, Center for Pediatric Cancer, National Cancer Center, Goyang, Republic of Korea.
Background/Aim:
Osteosarcoma is the most common type of bone cancer, but current therapeutic interventions remain largely insufficient. The development of new treatment strategies is needed, and moreover, optimal rodent models are necessary for testing the efficacy of new treatment modalities of osteosarcoma. Humanized mice carry human hematopoietic and immune systems, and are considered an ideal tool to study human diseases including cancer immunology. Herein, we performed a preliminary study toward developing an in vivo bioluminescent osteosarcoma model using humanized immunodeficient (NSG) mice.
Materials And Methods:
To establish the xenograft and orthotopic mouse model, NSG mice engrafted with human CD34+ hematopoietic stem cells were injected with luciferase-expressing KHOS/NP cells at two different time points. Bioluminescence images were obtained to monitor in vivo tumor growth and metastasis. Influence of the degree of human cell engraftment on tumor growth and metastatic behavior was analyzed and compared between the two groups.
Results:
KHOS/NP-luc cells injected in humanized NSG mice formed macroscopic tumors. The percentage of human CD45+ cells in these models was similar, but the percentage of human CD45+CD3+ and their subset was higher in the late-injection group compared to that of the early-injection group. The rate of KHOS/NP tumor growth was higher in the early-injection group than in the late-injection group. In the present study, human hematopoietic cell engraftment was not influenced by KHOS/NP cell injection, but KHOS/NP osteosarcoma showed more aggressive behavior in the early-injection group than that in the late-injection group, forming larger tumor volumes and earlier metastases.
Conclusion:
The results indicated that tumor growth and progression in humanized NSG mice may have been influenced by higher levels of human cell engraftment, especially T cells. Although there exist some limitations to our study, our preliminary results can provide the basis for the development of a humanized osteosarcoma mouse model.
Insights
Developing a humanized mouse model for osteosarcoma is crucial for new therapies. Early injection of cancer cells into humanized NSG mice led to more aggressive tumor growth and metastasis.
Area of Science:
- Immunology
- Oncology
- Preclinical Research
Background:
- Osteosarcoma, a common bone cancer, lacks effective treatments.
- Optimal preclinical models are essential for developing new therapeutic strategies.
- Humanized mice, possessing human immune systems, are valuable for cancer immunology studies.
Purpose of the Study:
- To develop an in vivo bioluminescent osteosarcoma model using humanized immunodeficient (NSG) mice.
- To assess the influence of human cell engraftment levels on tumor growth and metastasis.
- To establish a foundation for future osteosarcoma research in humanized models.
Main Methods:
- NSG mice were engrafted with human CD34+ hematopoietic stem cells.
- Luciferase-expressing KHOS/NP osteosarcoma cells were injected at two different time points (early vs. late).
- Bioluminescence imaging monitored tumor growth and metastasis; human cell engraftment was analyzed.
Main Results:
- Injected KHOS/NP-luc cells formed tumors in humanized NSG mice.
- Early injection of cancer cells resulted in higher tumor growth rates and earlier metastasis.
- Higher levels of human T cell engraftment correlated with more aggressive tumor progression.
Conclusions:
- Tumor progression in humanized NSG mice appears influenced by human cell engraftment, particularly T cells.
- This preliminary study provides a basis for developing humanized osteosarcoma mouse models.
- Further research is warranted to refine this model for therapeutic testing.
