使用高静水压抑制（HHP）灭活包含肿瘤的自体移植物，开发治疗恶性骨肿瘤的新型再生疗法。
Development of a novel regenerative therapy for malignant bone tumors using an autograft containing tumor inactivated by high hydrostatic pressurization (HHP).
发表日期：2023 Mar
作者：
Yuanjiaozi Li, Yasuhiro Katayama, Ie Nie, Takashi Nakano, Eiichi Sawaragi, Michiharu Sakamoto, Hiroki Yamanaka, Itaru Tsuge, Satoru Demura, Yohei Yamada, Hiroyuki Tsuchiya, Naoki Morimoto
来源：
Cell Death & Disease
摘要：
恶性骨肿瘤的手术切除会导致周围正常组织的明显缺陷，为避免截肢需进行修复。我们的研究旨在采用一种新型疗法——高静水压力（HHP）疗法，去除骨骼肉瘤（OS）影响的骨组织，以获得自体骨移植物，用于骨缺损修复。关键点是通过HHP实现完全肿瘤死亡，同时保留未变性的本地胞外基质（ECM）和骨组织。我们之前发现，HHP在200兆帕（MPa）下持续10分钟可以完全去除正常皮肤和皮肤肿瘤中的异常细胞，包括恶性黑色素瘤和鳞状细胞癌，同时保持它们的生化性能和生物组成。本研究基于之前的研究，使用HHP在200 MPa下持续10分钟将OS彻底去除。我们培养出一个OS细胞系（LM8），在200 MPa下持续10分钟进行加压处理，并通过形态学观察、WST-8测定和活死检测试实确认为失活。随后，我们将经过HHP处理或未经处理的OS细胞注入小鼠胫骨的骨髓中，然后将经过HHP处理或未经处理的肿瘤组织植入胫骨前部表面。经过HHP处理后，OS细胞没有增殖，并通过活死检测进行评估。加压处理的细胞和肿瘤在植入后没有增长。经过处理的骨组织已准备好作为无肿瘤的自体骨移植组织，从而完全根除了OS。这种简单和短压处理已被证明可以处理肿瘤影响的骨骼，制作出可移植和无肿瘤的自体骨代替物。© 2023日本再生医学学会。Elsevier B.V.生产和托管。
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.© 2023 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.