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Optimization of adipose tissue-derived mesenchymal stem cells by rapamycin in a murine model of acute graft-versus-host disease

Overview of attention for article published in Stem Cell Research & Therapy, October 2015
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Title
Optimization of adipose tissue-derived mesenchymal stem cells by rapamycin in a murine model of acute graft-versus-host disease
Published in
Stem Cell Research & Therapy, October 2015
DOI 10.1186/s13287-015-0197-8
Pubmed ID
Authors

Kyoung-Woon Kim, Su-Jin Moon, Min-Jung Park, Bo-Mi Kim, Eun-Kyung Kim, Sung-Hee Lee, Eun-Jung Lee, Byung-Ha Chung, Chul-Woo Yang, Mi-La Cho

Abstract

Mesenchymal stem cells (MSCs) can protect bone marrow transplantation (BMT) recipients from the lethal acute graft-versus-host disease (aGVHD) development. However, the mechanisms underlying the anti-inflammatory properties of MSCs in aGVHD remain to be elucidated. The immunoregulatory properties of MSCs are mediated by their production of anti-inflammatory molecules, including IL-10 and TGF-β. On the other hand, MSCs can also produce proinflammatory cytokines during their normal growth, such as IL-1β and IL-6. These opposite actions may limit their therapeutic application in aGVHD. Therefore, optimization of the functional properties of MSCs can increase their benefits. The expressions of mRNA and protein were analyzed by real-time PCR and western blotting, respectively. Expression of MSC markers was assessed by flow cytometry. An animal model of aGVHD was established by transplanting C57BL/6 donor bone marrow cells and spleen cells into lethally irradiated BALB/c recipient mice. The recipient mice were divided into the control group and the therapy [adipose tissue-derived human MSCs (Ad-hMSCs) or rapamycin-treated Ad-hMSCs] groups. The survival, body weight and clinical score of aGVHD in transplanted mice were monitored. Rapamycin pre-treatment of Ad-hMSCs increased mRNA synthesis of IL-10, indoleamine 2,3-dioxygenase, and TGF-β compared with untreated Ad-hMSCs. Rapamycin-treated Ad-hMSCs suppressed clonal expansion of interleukin-17-producing CD4(+) T (Th17) cells more effectively than untreated cells. mRNA expression of autophagy markers such as ATG5, LC3A and LC3B was significantly increased in the rapamycin-treated Ad-hMSCs compared with untreated Ad-hMSCs. Transmission electron microscopy revealed that Ad-hMSCs exposure to rapamycin resulted in the appearance of autophagic vacuoles. Interestingly, in vitro migration efficiency of rapamycin-treated Ad-hMSCs toward the CD4(+) T cells was increased significantly compared with the untreated cells. And, these effects were associated with autophagy induction capacity of rapamycin. In vivo, the inhibiting properties of MSCs on the clinical severities of aGVHD were greater in the mice receiving rapamycin-treated Ad-hMSCs compared with untreated Ad-hMSCs. The beneficial effects of rapamycin treatment in Ad-hMSCs shown in vivo were associated with a reduction of Th17 cells and an increase in regulatory T cells. Rapamycin can optimize the immunomodulatory potential of Ad-hMSCs, suggesting a promising strategy of MSC use in aGVHD treatment.

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X Demographics

The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 57 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
Unknown 56 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 23%
Student > Ph. D. Student 13 23%
Student > Master 6 11%
Student > Bachelor 4 7%
Student > Doctoral Student 3 5%
Other 8 14%
Unknown 10 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 21%
Medicine and Dentistry 12 21%
Agricultural and Biological Sciences 4 7%
Immunology and Microbiology 3 5%
Pharmacology, Toxicology and Pharmaceutical Science 2 4%
Other 8 14%
Unknown 16 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 02 August 2016.
All research outputs
#20,336,685
of 22,881,964 outputs
Outputs from Stem Cell Research & Therapy
#2,050
of 2,425 outputs
Outputs of similar age
#237,965
of 283,679 outputs
Outputs of similar age from Stem Cell Research & Therapy
#53
of 60 outputs
Altmetric has tracked 22,881,964 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,425 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.0. This one is in the 1st percentile – i.e., 1% 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 283,679 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 60 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.