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

Overview of attention for article published in Stem Cell Research & Therapy, April 2017
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3 tweeters

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37 Mendeley
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Title
Xenotransplantation of interferon-gamma-pretreated clumps of a human mesenchymal stem cell/extracellular matrix complex induces mouse calvarial bone regeneration
Published in
Stem Cell Research & Therapy, April 2017
DOI 10.1186/s13287-017-0550-1
Pubmed ID
Authors

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

Abstract

Three-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. Human bone marrow-derived MSCs were seeded at a density of 2.0 × 10(5) cells/well into 24-well plates and cultured with growth medium supplemented with 50 μg/mL L-ascorbic acid for 4 days. To obtain C-MSC, confluent cells that had formed on the cellular sheet were scratched using a micropipette tip and were then torn off. The cellular sheet was rolled to make a round clump of cells. C-MSC was stimulated with IFN-γ and IDO expression, immunosuppressive capacity, and immunophenotype were evaluated in vitro. Moreover, C-MSC or C-MSCγ was xenotransplanted into immunocompetent or immunodeficient mice calvarial defect models without artificial scaffold, respectively. IFN-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. Xenotransplantation 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.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 37 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 19%
Student > Bachelor 4 11%
Student > Master 3 8%
Student > Postgraduate 3 8%
Student > Doctoral Student 2 5%
Other 5 14%
Unknown 13 35%
Readers by discipline Count As %
Medicine and Dentistry 10 27%
Biochemistry, Genetics and Molecular Biology 5 14%
Agricultural and Biological Sciences 3 8%
Materials Science 2 5%
Unspecified 1 3%
Other 4 11%
Unknown 12 32%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 May 2017.
All research outputs
#5,233,590
of 9,770,649 outputs
Outputs from Stem Cell Research & Therapy
#471
of 871 outputs
Outputs of similar age
#135,330
of 262,846 outputs
Outputs of similar age from Stem Cell Research & Therapy
#18
of 29 outputs
Altmetric has tracked 9,770,649 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 871 research outputs from this source. They receive a mean Attention Score of 5.0. This one is in the 40th percentile – i.e., 40% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 262,846 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 29 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.