Evidence map›Paper›PMID 27764795›Full record

ArticleOncotarget2016

A novel 3D mesenchymal stem cell model of the multiple myeloma bone marrow niche: biologic and clinical applications.

Jana Jakubikova, Danka Cholujova, Teru Hideshima, Paulina Gronesova, Andrea Soltysova, Takeshi Harada, Jungnam Joo, Sun-Young Kong, Raphael E Szalat, Paul G Richardson and 3 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.6field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 65 citations in OpenAlex.

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  7. A 3D engineered multiple myeloma niche for evaluating CAR T cell therapy.Frontiers in bioengineering and biotechnology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 3 countries.

Jana JakubikovaDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USA.
Danka CholujovaCancer Research Institute, Biomedical Research Center SAS, Bratislava, Slovak Republic.
Teru HideshimaDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USA.
Paulina GronesovaCancer Research Institute, Biomedical Research Center SAS, Bratislava, Slovak Republic.
Andrea SoltysovaDepartment of Molecular Biology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovak Republic.
Takeshi HaradaDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USA.
Jungnam JooBiometric Research Branch, Division of Cancer Epidemiology and Prevention, Research Institute & Hospital, National Cancer Center, Goyang-si Gyeonggi-do, South Korea.
Sun-Young KongDepartment of Laboratory Medicine and Translational Epidemiology Branch, Research Institute & Hospital, National Cancer Center, Goyang-si Gyeonggi-do, South Korea.
Raphael E SzalatDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USA.
Paul G RichardsonDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USA.
Nikhil C MunshiDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USA.
David M DorfmanDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Kenneth C AndersonDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USA.
Harvard University · USCancer Research Institute of the Slovak Academy of Sciences · SKDana-Farber Cancer Institute · USNational Cancer Center · KRComenius University Bratislava · SK

Funding

Trageting the Multiple Myeloma EpigenomeP50CA100707 · NCI · DANA-FARBER CANCER INSTITUTE · PI ANDERSON, KENNETH C., MUNSHI, NIKHIL C. · 2003 to 2023
$45.0M
NCI NIH HHS P50 CA100707
6 · The paper itself

Abstract

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.

Indexed as

Models, BiologicalBiomarkers, TumorCell DifferentiationCell ProliferationCoculture TechniquesHumansMesenchymal Stem CellsMonocytesMultiple MyelomaStem Cell NicheTumor MicroenvironmentBiomarkers, Tumor3D modeldrug resistancemesenchymal stem cellsmultiple myelomatumor microenvironment

Identifiers

PMID27764795
PMCPMC5357212
OpenAlexW2530396113

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.