Development of a 3D bone marrow adipose tissue model.
Development of a 3D bone marrow adipose tissue model.
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DOI：
10.1016/j.bone.2018.01.023
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发表时间：
2019-01
期刊：
影响因子：
4.1
通讯作者：
Reagan MR
中科院分区：
文献类型：
--
作者：
Fairfield H;Falank C;Farrell M;Vary C;Boucher JM;Driscoll H;Liaw L;Rosen CJ;Reagan MR
在过去的二十年中，已经积累的证据表明，生物化学和空间定义的细胞外基质，细胞组分和相互作用的网络决定了细胞分化，增殖和在各种组织和疾病中的功能。在体外对体内系统进行建模是非常必要的，但是当使用简化的2D条件而不是3D体外模型时，从这些模型获得的数据的可靠性和有用性降低。因此，迫切需要开发和验证可靠的体外模型，以再现特定的组织样结构，并以更现实的方式模拟细胞的功能和反应，用于药物筛选/疾病建模和组织再生应用。在脂肪生物学和癌症研究中，这些模型作为生理相关的3D平台，弥合了2D培养和体内模型之间的鸿沟，带来了更可靠和更有用的数据，以加速从实验室到临床的研究。目前，还没有开发出骨髓脂肪组织（BMAT）的模型，BMAT是一种新的脂肪库，以前被忽视为“填充组织”，但最近被认为是内分泌信号传导和全身相关的。在这里，我们描述了第一个3D，BMAT模型的发展，来自人类或小鼠骨髓（BM）间充质基质细胞（MSC）。我们发现BMAT模型可以在体外稳定培养至少3个月，并且骨髓瘤细胞（5 TGM 1、OPM 2和MM 1 S细胞）可以在这些模型上培养至少2周。在肿瘤细胞共培养后，BMAT脂肪细胞中发生脱脂，表明这两种重要细胞类型在恶性BM生态位中存在双向关系。总体而言，我们的研究表明，3D BMAT代表了一种“更健康”，更真实的组织模型，可能有助于阐明MAT对肿瘤细胞的影响，以及肿瘤细胞对MAT的影响，以确定新的治疗靶点。此外，蛋白质组学表征以及微阵列数据（> 22，000个基因的表达）与KEGG途径分析和基因集表达分析（GSEA）相结合，支持我们开发与2D培养相比炎症更少的3D BMAT。总之，我们开发了第一个3D组织工程骨髓脂肪组织模型，这是一种多功能的新型模型，可用于研究与骨髓相关的许多疾病和生物学过程。
Over the past twenty years, evidence has accumulated that biochemically and spatially defined networks of extracellular matrix, cellular components, and interactions dictate cellular differentiation, proliferation, and function in a variety of tissue and diseases. Modeling in vivo systems in vitro has been undeniably necessary, but when simplified 2D conditions rather than 3D in vitro models are used, the reliability and usefulness of the data derived from these models decreases. Thus, there is a pressing need to develop and validate reliable in vitro models to reproduce specific tissue-like structures and mimic functions and responses of cells in a more realistic manner for both drug screening/disease modeling and tissue regeneration applications. In adipose biology and cancer research, these models serve as physiologically relevant 3D platforms to bridge the divide between 2D cultures and in vivo models, bringing about more reliable and translationally useful data to accelerate benchtop to bedside research. Currently, no model has been developed for bone marrow adipose tissue (BMAT), a novel adipose depot that has previously been overlooked as “filler tissue” but has more recently been recognized as endocrine-signaling and systemically relevant. Herein we describe the development of the first 3D, BMAT model derived from either human or mouse bone marrow (BM) mesenchymal stromal cells (MSCs). We found that BMAT models can be stably cultured for at least 3 months in vitro, and that myeloma cells (5TGM1, OPM2 and MM1S cells) can be cultured on these for at least 2 weeks. Upon tumor cell co-culture, delipidation occurred in BMAT adipocytes, suggesting a bidirectional relationship between these two important cell types in the malignant BM niche. Overall, our studies suggest that 3D BMAT represents a “healthier,” more realistic tissue model that may be useful for elucidating the effects of MAT on tumor cells, and tumor cells on MAT, to identify novel therapeutic targets. In addition, proteomic characterization as well as microarray data (expression of >22,000 genes) coupled with KEGG pathway analysis and gene set expression analysis (GSEA) supported our development of less-inflammatory 3D BMAT compared to 2D culture. In sum, we developed the first 3D, tissue-engineered bone marrow adipose tissue model, which is a versatile, novel model that can be used to study numerous diseases and biological processes involved with the bone marrow.
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影响因子：
10
作者：
Abbott RD;Wang RY;Reagan MR;Chen Y;Borowsky FE;Zieba A;Marra KG;Rubin JP;Ghobrial IM;Kaplan DL
通讯作者：
Kaplan DL
影响因子：
5.6
作者：
Doucette CR;Horowitz MC;Berry R;MacDougald OA;Anunciado-Koza R;Koza RA;Rosen CJ
通讯作者：
Rosen CJ
影响因子：
24.7
作者：
Chang, Su-Hsin;Luo, Suhong;O'Brian, Katiuscia K.;Thomas, Theodore S.;Colditz, Graham A.;Carlsson, Nils P.;Carson, Kenneth R.
通讯作者：
Carson, Kenneth R.
影响因子：
6.2
作者：
Devlin, Maureen J.;Cloutier, Alison M.;Thomas, Nishina A.;Panus, David A.;Lotinun, Sutada;Pinz, Ilka;Baron, Roland;Rosen, Clifford J.;Bouxsein, Mary L.
通讯作者：
Bouxsein, Mary L.
影响因子：
14
作者：
Fong EL;Wan X;Yang J;Morgado M;Mikos AG;Harrington DA;Navone NM;Farach-Carson MC
通讯作者：
Farach-Carson MC