Haematopoietic Stem Cell Lab, The Francis Crick Institute, London, UK.
Department of Haematology, School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
Methods Mol Biol. 2021;2308:235-251. doi: 10.1007/978-1-0716-1425-9_18.
Over the last 20 years, significant progress has been made in the development of immunodeficient mouse models that now represents the gold standard tool in stem cell biology research. The latest major improvement has been the use of biomaterials in these xenogeneic mouse models to generate human "bone marrow like" tissues, which not only provides a more relevant xenograft model but can also potentially enable us to delineate the interactions that are specific between human bone marrow cells. There are a number of biomaterials and strategies to create humanized niches in immunodeficient mouse models, and the methods can also differ significantly among various research institutes. Here, we describe a protocol to create a humanized 3D collagen-based scaffold human niche in immunodeficient mouse model(s). This humanized in vivo model provides a powerful technique for understanding the human BM microenvironment and the role it plays in the regulation of normal as well as malignant hematopoiesis.
在过去的 20 年中,免疫缺陷型小鼠模型的发展取得了重大进展,目前它是干细胞生物学研究的金标准工具。最近的一项重大改进是在这些异种移植小鼠模型中使用生物材料来生成类似于人类“骨髓”的组织,这不仅提供了一个更相关的异种移植模型,还可能使我们能够描绘出人类骨髓细胞之间的特异性相互作用。有许多生物材料和策略可用于在免疫缺陷型小鼠模型中创建人类化小生境,并且这些方法在不同的研究机构之间也可能有很大的差异。在这里,我们描述了一种在免疫缺陷型小鼠模型中创建基于胶原的 3D 人源化支架小生境的方案。这种人源化的体内模型为理解人类 BM 微环境及其在调节正常和恶性造血中的作用提供了一种强大的技术。