Schuster James, Zhang Jun, Longo Maria
Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19072, USA.
J Neurosurg Spine. 2006 May;4(5):388-91. doi: 10.3171/spi.2006.4.5.388.
One of the major difficulties of conducting bone metastasis research is the lack of adequate models for studying the bone-tumor microenvironment. The limitations of current in vivo models include the following: non-human tumor or bone, variable reproducibility, limited supply, and an inability to be easily manipulated. The objective of the present study was to develop a uniform and reproducible model of bone/spine metastasis by utilizing bone derived from human osteoblasts grown subcutaneously in severe combined immunodeficiency (SCID) mice with subsequent introduction of human carcinoma cell lines.
Human osteoblasts were serially passed in culture and induced to differentiate into mature osteoblasts. They were subsequently loaded on hydroxyapatite-coated collagen sponges and implanted subcutaneously into the SCID mice. After allowing the bone to mature for 8 weeks, tumor cell suspensions were implanted percutaneously into the bone. The bone-tumor complexes were subsequently harvested, decalcified, and prepared for histological examination.
The authors have developed a novel, reproducible SCID mouse model of bone/spine metastasis by using bone derived from human osteoblasts and subsequently introduced human tumor lines. They believe this model will be useful for studying the basic biology of bone metastases.
开展骨转移研究的主要困难之一是缺乏用于研究骨 - 肿瘤微环境的合适模型。当前体内模型的局限性包括:非人类肿瘤或骨骼、可重复性不一、供应有限以及难以轻易操控。本研究的目的是通过利用在严重联合免疫缺陷(SCID)小鼠皮下生长的人成骨细胞衍生的骨,随后引入人癌细胞系,来建立一个统一且可重复的骨/脊柱转移模型。
人成骨细胞在培养中连续传代并诱导分化为成熟成骨细胞。随后将它们加载到羟基磷灰石涂层的胶原海绵上,并皮下植入SCID小鼠体内。在使骨成熟8周后,将肿瘤细胞悬液经皮植入骨中。随后收获骨 - 肿瘤复合物,进行脱钙,并准备进行组织学检查。
作者通过使用人成骨细胞衍生的骨并随后引入人肿瘤细胞系,建立了一种新型的、可重复的骨/脊柱转移SCID小鼠模型。他们认为该模型将有助于研究骨转移的基础生物学。