Evidence map›Paper›PMID 35563880›Full record

ArticleCells2022

Growth Response and Differentiation of Bone Marrow-Derived Mesenchymal Stem/Stromal Cells in the Presence of Novel Multiple Myeloma Drug Melflufen.

Arjen Gebraad, Roope Ohlsbom, Juho J Miettinen, Promise Emeh, Toni-Karri Pakarinen, Mikko Manninen, Antti Eskelinen, Kirsi Kuismanen, Ana Slipicevic, Fredrik Lehmann and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 21% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Review
  3. mTORC1 regulates the proliferation of SOX9Histochemistry and cell biology · 2025
    Article
  4. Review
  5. Review
  6. Review
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 2 countries.

Arjen GebraadAdult Stem Cell Group, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland.ORCID 0000-0001-5774-237X
Roope OhlsbomAdult Stem Cell Group, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland.
Juho J MiettinenInstitute for Molecular Medicine Finland-FIMM, HiLIFE-Helsinki Institute of Life Science, iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, 00290 Helsinki, Finland.ORCID 0000-0002-3987-1693
Promise EmehAdult Stem Cell Group, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland.ORCID 0000-0002-2546-3816
Toni-Karri PakarinenDepartment of Musculoskeletal Diseases, Tampere University Hospital, 33520 Tampere, Finland.
Mikko ManninenOrton Orthopaedic Hospital, 00280 Helsinki, Finland.
Antti EskelinenCoxa Hospital for Joint Replacement, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland.
Kirsi KuismanenDepartment of Obstetrics and Gynecology, Tampere University Hospital, 33520 Tampere, Finland.
Ana SlipicevicOncopeptides AB, 111 37 Stockholm, Sweden.
Fredrik LehmannOncopeptides AB, 111 37 Stockholm, Sweden.ORCID 0000-0001-7385-3870
Nina N NupponenOncopeptides AB, 111 37 Stockholm, Sweden.
Caroline A HeckmanInstitute for Molecular Medicine Finland-FIMM, HiLIFE-Helsinki Institute of Life Science, iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, 00290 Helsinki, Finland.ORCID 0000-0002-4324-8706
Susanna MiettinenAdult Stem Cell Group, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland.
Tampere University · FIOncopeptides (Sweden) · SETampere University Hospital · FIUniversity of Helsinki · FIInvalidisäätiö · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mesenchymal stem/stromal cells (MSCs) are self-renewing and multipotent progenitors, which constitute the main cellular compartment of the bone marrow stroma. Because MSCs have an important role in the pathogenesis of multiple myeloma, it is essential to know if novel drugs target MSCs. Melflufen is a novel anticancer peptide-drug conjugate compound for patients with relapsed refractory multiple myeloma. Here, we studied the cytotoxicity of melflufen, melphalan and doxorubicin in healthy human bone marrow-derived MSCs (BMSCs) and how these drugs affect BMSC proliferation. We established co-cultures of BMSCs with MM.1S myeloma cells to see if BMSCs increase or decrease the cytotoxicity of melflufen, melphalan, bortezomib and doxorubicin. We evaluated how the drugs affect BMSC differentiation into adipocytes and osteoblasts and the BMSC-supported formation of vascular networks. Our results showed that BMSCs were more sensitive to melflufen than to melphalan. The cytotoxicity of melflufen in myeloma cells was not affected by the co-culture with BMSCs, as was the case for melphalan, bortezomib and doxorubicin. Adipogenesis, osteogenesis and BMSC-mediated angiogenesis were all affected by melflufen. Melphalan and doxorubicin affected BMSC differentiation in similar ways. The effects on adipogenesis and osteogenesis were not solely because of effects on proliferation, seen from the differential expression of differentiation markers normalized by cell number. Overall, our results indicate that melflufen has a significant impact on BMSCs, which could possibly affect therapy outcome.

Indexed as

Mesenchymal Stem CellsMultiple MyelomaBone MarrowBortezomibDoxorubicinHumansMelphalanPhenylalanineBortezomibDoxorubicinmelflufenMelphalanPhenylalanineadipogenesisangiogenesisbone marrowdrug sensitivitymelflufenmelphalan flufenamidemesenchymal stem/stromal cellsmultiple myelomaosteogenesispeptide–drug conjugate

Identifiers

PMID35563880
PMCPMC9103864
OpenAlexW4229332208

What OpenQuestion holds

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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.