Arthritis Centre of Excellence and Toronto Western Hospital Research Institute, Division of Genetics and Development, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
J Rheumatol. 2010 Mar;37(3):496-502. doi: 10.3899/jrheum.090317. Epub 2010 Jan 28.
Studies of human inflammatory arthritis would be significantly aided by the development of better animal models. Our hypothesis is that it is possible to develop humanized arthritis models through novel techniques of hematopoietic stem and progenitor cell (HSPC) delivery.
Bone marrow was obtained from patients with osteoarthritis who were undergoing total hip replacement. HSPC were enriched by negative selection and injected into the femur of irradiated anti-CD122 treated nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Human cell engraftment was analyzed by flow cytometry. Arthritis was induced by an intraarticular injection of Chlamydia trachomatis and injected knee joints were examined 5 days later by histology and immunohistochemistry.
Human bone marrow HSPC successfully engrafted NOD/SCID mice, with some mice showing up to 90% engrafted human cells. Human B lymphoid and myeloid cells were detected in the bone marrow and spleen 6 weeks following transfer of HSPC, and engrafted recipient mice remained healthy up to 12 weeks postinjection. Chlamydia-injected mice that had been repopulated with HSPC had synovial inflammation, consisting of human neutrophils and macrophages.
Bone marrow-derived human HSPC engraft NOD/SCID mice and traffic appropriately to an inflammatory stimulus in the joint, thus offering the potential for direct studies on the immunopathogenesis and treatment of human arthritis.
通过造血干细胞和祖细胞（HSPC）传递的新技术，开发出更优秀的动物模型，将极大地促进人类炎症性关节炎的研究。我们的假设是，通过新型造血干细胞和祖细胞（HSPC）传递技术，有可能开发出人类关节炎模型。
从接受全髋关节置换术的骨关节炎患者中获取骨髓。通过阴性选择对 HSPC 进行富集，并将其注入经辐照的抗-CD122 处理的非肥胖型糖尿病/严重联合免疫缺陷（NOD/SCID）小鼠的股骨中。通过流式细胞术分析人细胞植入情况。通过关节内注射沙眼衣原体来诱导关节炎，然后在第 5 天通过组织学和免疫组织化学检查注射膝关节。
人类骨髓 HSPC 成功植入 NOD/SCID 小鼠，有些小鼠的人细胞植入率高达 90%。在 HSPC 转移后 6 周，骨髓和脾脏中检测到人类 B 淋巴样细胞和髓样细胞，并且在注射后 12 周内植入的受者小鼠仍然健康。用 HSPC 重新填充的接种衣原体的小鼠出现了滑膜炎症，其中包括人类中性粒细胞和巨噬细胞。
骨髓来源的人类 HSPC 植入 NOD/SCID 小鼠，并适当地迁移到关节中的炎症刺激部位，从而为研究人类关节炎的免疫发病机制和治疗提供了可能。
