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Updated: Aug 6, 2025
Modeling Primary Bone Tumors and Bone Metastasis with Solid Tumor Graft Implantation into Bone
Published on: September 9, 2020
Development of a novel regenerative therapy for malignant bone tumors using an autograft containing tumor inactivated
Yuanjiaozi Li1, Yasuhiro Katayama1, Ie Nie1
1Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Abstract:
Surgical resection of malignant bone tumors leads to significant defects in the normal surrounding tissues that should be reconstructed to avoid amputation. Our research aimed to inactivate osteosarcoma (OS)-affected bone to obtain autologous bone grafts for bone defect reconstruction using a novel therapy called high hydrostatic pressurization (HHP) therapy. The key points are complete tumor death and preservation of the non-denatured native extracellular matrix (ECM) and bone tissue by HHP. Previously, we found that HHP at 200 MPa for 10 min can completely inactivate cells in normal skin and skin tumors, including malignant melanoma and squamous cell carcinoma while maintaining their original biochemical properties and biological components. Based on our previous research, this study used HHP at 200 MPa for 10 min to eradicate OS. We prepared an OS cell line (LM8), pressurized it at 200 MPa for 10 min, and confirmed its inactivation through morphological observation, WST-8 assay, and live/dead assay. We then injected OS cells with or without HHP into the bone marrow of the murine tibia, after which we implanted tumor tissues with or without HHP into the anterior surface of the tibia. After HHP, OS cells did not proliferate and were assessed using a live/dead assay. The pressurized cells and tumors did not grow after implantation. The pressurized bone was well prepared as tumor-free autologous bone tissues, resulting in the complete eradication of OS. This straightforward and short-pressing treatment was proven to process the tumor-affected bone to make a transplantable and tumor-free autologous bone substitute.
Insights
High hydrostatic pressurization (HHP) therapy effectively inactivates osteosarcoma (OS) cells and tumors. This novel approach preserves bone tissue, creating tumor-free autologous grafts for defect reconstruction and avoiding amputation.
Area of Science:
- Biomedical Engineering
- Oncology
- Regenerative Medicine
Background:
- Surgical resection of malignant bone tumors creates defects requiring reconstruction to prevent amputation.
- Autologous bone grafts are ideal for reconstruction but pose challenges when contaminated with tumors.
- Novel methods are needed to eliminate tumor cells while preserving graft viability.
Purpose of the Study:
- To evaluate high hydrostatic pressurization (HHP) therapy for inactivating osteosarcoma (OS) cells and bone.
- To determine if HHP can create tumor-free autologous bone grafts for defect reconstruction.
- To assess the preservation of native bone extracellular matrix (ECM) after HHP treatment.
Main Methods:
- Osteosarcoma (OS) cell line (LM8) and tumor tissues were subjected to HHP at 200 MPa for 10 minutes.
- Cell inactivation was confirmed using morphological observation, WST-8 assay, and live/dead assay.
- Inactivated OS cells and tissues were implanted into murine tibias to assess tumor growth and graft viability.
Main Results:
- HHP treatment at 200 MPa for 10 minutes completely inactivated OS cells.
- Inactivated OS cells and tumors did not proliferate after implantation.
- HHP-treated bone was successfully prepared as tumor-free autologous bone tissue, demonstrating complete OS eradication.
Conclusions:
- High hydrostatic pressurization (HHP) is a viable method for eradicating osteosarcoma in bone.
- HHP preserves the native bone extracellular matrix (ECM), enabling the creation of transplantable, tumor-free autologous bone grafts.
- This technique offers a promising solution for reconstructing bone defects caused by malignant bone tumors, potentially avoiding amputation.
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