Evidence map›Paper›PMID 28446226›Full record

ArticleStem cell research & therapy2017

Xenotransplantation of interferon-gamma-pretreated clumps of a human mesenchymal stem cell/extracellular matrix complex induces mouse calvarial bone regeneration.

Kei Takeshita, Souta Motoike, Mikihito Kajiya, Nao Komatsu, Manabu Takewaki, Kazuhisa Ouhara, Tomoyuki Iwata, Katsuhiro Takeda, Noriyoshi Mizuno, Tsuyoshi Fujita and 1 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

24 citing papers in PubMed, 38 citations in OpenAlex.

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  14. IFN-BioMed research international · 2021
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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

11 authors at 1 institution in 1 country.

Kei TakeshitaDepartment of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Souta MotoikeDepartment of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Mikihito KajiyaDepartment of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan. mkajiya@hiroshima-u.ac.jp.
Nao KomatsuDepartment of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Manabu TakewakiDepartment of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Kazuhisa OuharaDepartment of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Tomoyuki IwataDepartment of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Katsuhiro TakedaDepartment of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Noriyoshi MizunoDepartment of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Tsuyoshi FujitaDepartment of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Hidemi KuriharaDepartment of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Hiroshima University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThree-dimensional cultured clumps of a mesenchymal stem cell (MSC)/extracellular matrix (ECM) complex (C-MSC) consists of cells and self-produced ECM. C-MSC can regulate the cellular function in vitro and induce successful bone regeneration using ECM as a cell scaffold. Potentiating the immunomodulatory capacity of C-MSCs, which can ameliorate the allo-specific immune response, may be helpful in developing beneficial "off-the-shelf" cell therapy for tissue regeneration. It is well reported that interferon (IFN)-γ stimulates the immunosuppressive properties of MSC via upregulation of the immunomodulatory enzyme IDO. Therefore, the aim of this study was to investigate the effect of IFN-γ on the immunomodulatory capacity of C-MSC in vitro and to test the bone regenerative activity of C-MSC or IFN-γ-pretreated C-MSC (C-MSCγ) xenografts in a mice calvarial defect model.

methodsHuman bone marrow-derived MSCs were seeded at a density of 2.0 × 10

resultsIFN-γ stimulated IDO expression in C-MSC. C-MSCγ, but not C-MSC, attenuated CD3/CD28-induced T cell proliferation and its suppressive effect was reversed by an IDO inhibitor. C-MSCγ showed upregulation of HLA-DR expression, but its co-stimulatory molecule, CD86, was not detected. Xenotransplantation of C-MSCγ into immunocompetent mice calvarial defect induced bone regeneration, whereas C-MSC xenograft failed and induced T cell infiltration in the grafted area. On the other hand, both C-MSC and C-MSCγ xenotransplantation into immunodeficient mice caused bone regeneration.

conclusionsXenotransplantation of C-MSCγ, which exerts immunomodulatory properties via the upregulation of IDO activity in vitro, may attenuate xenoreactive host immune response, and thereby induce bone regeneration in mice. Accordingly, C-MSCγ may constitute a promising novel allograft cell therapy for bone regeneration.

Indexed as

Mesenchymal Stem Cell TransplantationAnimalsAscorbic AcidBone Marrow CellsBone RegenerationCell ProliferationCells, CulturedDisease Models, AnimalHLA-DR AntigensHumansIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaLeukocytes, MononuclearMaleMesenchymal Stem CellsMiceAscorbic AcidHLA-DR AntigensIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaC-MSCIDOIFN-γXenotransplantation

Identifiers

PMID28446226
PMCPMC5406942
OpenAlexW2608026155

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Registered trials

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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.