| Item type |
文献 / Documents(1) |
| 公開日 |
2019-12-10 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
|
|
関連識別子 |
https://doi.org/10.18632/oncotarget.12643 |
|
|
関連名称 |
10.18632/oncotarget.12643 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
A novel 3D mesenchymal stem cell model of the multiple myeloma bone marrow niche : biologic and clinical applications |
| 著者 |
Jakubikova, Jana
Cholujova, Danka
ヒデシマ, テル
Gronesova, Paulina
Soltysova, Andrea
原田, 武志
Joo, Jungnam
Kong, Sun-Young
Szalat, Raphael E.
Richardson, Paul G.
Munshi, Nikhil C.
Dorfman, David M.
Anderson, Kenneth C.
|
| 抄録 |
|
|
内容記述 |
Specific niches within the tumor bone marrow (BM) microenvironment afford a sanctuary for multiple myeloma (MM) clones due to stromal cell-tumor cell interactions, which confer survival advantage and drug resistance. Defining the sequelae of tumor cell interactions within the MM niches on an individualized basis may provide the rationale for personalized therapies. To mimic the MM niche, we here describe a new 3D co-culture ex-vivo model in which primary MM patient BM cells are co-cultured with mesenchymal stem cells (MSC) in a hydrogel 3D system. In the 3D model, MSC with conserved phenotype (CD73+CD90+CD105+) formed compact clusters with active fibrous connections, and retained lineage differentiation capacity. Extracellular matrix molecules, integrins, and niche related molecules including N-cadherin and CXCL12 are expressed in 3D MSC model. Furthermore, activation of osteogenesis (MMP13, SPP1, ADAMTS4, and MGP genes) and osteoblastogenic differentiation was confirmed in 3D MSC model. Co-culture of patient-derived BM mononuclear cells with either autologous or allogeneic MSC in 3D model increased proliferation of MM cells, CXCR4 expression, and SP cells. We carried out immune profiling to show that distribution of immune cell subsets was similar in 3D and 2D MSC model systems. Importantly, resistance to novel agents (IMiDs, bortezomib, carfilzomib) and conventional agents (doxorubicin, dexamethasone, melphalan) was observed in 3D MSC system, reflective of clinical resistance. This 3D MSC model may therefore allow for studies of MM pathogenesis and drug resistance within the BM niche. Importantly, ongoing prospective trials are evaluating its utility to inform personalized targeted and immune therapy in MM. |
| キーワード |
|
|
主題 |
multiple myeloma |
| キーワード |
|
|
主題 |
tumor microenvironment |
| キーワード |
|
|
主題 |
mesenchymal stem cells |
| キーワード |
|
|
主題 |
3D model |
| キーワード |
|
|
主題 |
drug resistance |
| 書誌情報 |
en : Oncotarget
巻 7,
号 47,
p. 77326-77341,
発行日 2016-10-13
|
| 収録物ID |
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|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
19492553 |
| 出版者 |
|
|
出版者 |
Impact Journals |
| 権利情報 |
|
|
権利情報 |
This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| EID |
|
|
識別子 |
349638 |
| 言語 |
|
|
言語 |
eng |
onc_7_47_77326.pdf (6.41 MB)
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