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Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect model

Overview of attention for article published in Stem Cell Research & Therapy, January 2018
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (79th percentile)
  • High Attention Score compared to outputs of the same age and source (93rd percentile)

Mentioned by

blogs
1 blog
twitter
3 tweeters

Readers on

mendeley
33 Mendeley
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Title
Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect model
Published in
Stem Cell Research & Therapy, January 2018
DOI 10.1186/s13287-017-0754-4
Pubmed ID
Authors

Akiko Saito, Akio Ooki, Takashi Nakamura, Shoko Onodera, Kamichika Hayashi, Daigo Hasegawa, Takahito Okudaira, Katsuhito Watanabe, Hiroshi Kato, Takeshi Onda, Akira Watanabe, Kenjiro Kosaki, Ken Nishimura, Manami Ohtaka, Mahito Nakanishi, Teruo Sakamoto, Akira Yamaguchi, Kenji Sueishi, Toshifumi Azuma

Abstract

Runt-related transcription factor 2 (RUNX2) haploinsufficiency causes cleidocranial dysplasia (CCD) which is characterized by supernumerary teeth, short stature, clavicular dysplasia, and osteoporosis. At present, as a therapeutic strategy for osteoporosis, mesenchymal stem cell (MSC) transplantation therapy is performed in addition to drug therapy. However, MSC-based therapy for osteoporosis in CCD patients is difficult due to a reduction in the ability of MSCs to differentiate into osteoblasts resulting from impaired RUNX2 function. Here, we investigated whether induced pluripotent stem cells (iPSCs) properly differentiate into osteoblasts after repairing the RUNX2 mutation in iPSCs derived from CCD patients to establish normal iPSCs, and whether engraftment of osteoblasts derived from properly reverted iPSCs results in better regeneration in immunodeficient rat calvarial bone defect models. Two cases of CCD patient-derived induced pluripotent stem cells (CCD-iPSCs) were generated using retroviral vectors (OCT3/4, SOX2, KLF4, and c-MYC) or a Sendai virus SeVdp vector (KOSM302L). Reverted iPSCs were established using programmable nucleases, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-derived RNA-guided endonucleases, to correct mutations in CCD-iPSCs. The mRNA expressions of osteoblast-specific markers were analyzed using quantitative reverse-transcriptase polymerase chain reaction. iPSCs-derived osteoblasts were transplanted into rat calvarial bone defects, and bone regeneration was evaluated using microcomputed tomography analysis and histological analysis. Mutation analysis showed that both contained nonsense mutations: one at the very beginning of exon 1 and the other at the initial position of the nuclear matrix-targeting signal. The osteoblasts derived from CCD-iPSCs (CCD-OBs) expressed low levels of several osteoblast differentiation markers, and transplantation of these osteoblasts into calvarial bone defects created in rats with severe combined immunodeficiency showed poor regeneration. However, reverted iPSCs improved the abnormal osteoblast differentiation which resulted in much better engraftment into the rat calvarial bone defect. Taken together, these results demonstrate that patient-specific iPSC technology can not only provide a useful disease model to elucidate the role of RUNX2 in osteoblastic differentiation but also raises the tantalizing prospect that reverted iPSCs might provide a practical medical treatment for CCD.

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 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 33 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 15%
Student > Master 4 12%
Professor > Associate Professor 4 12%
Student > Bachelor 3 9%
Student > Doctoral Student 3 9%
Other 7 21%
Unknown 7 21%
Readers by discipline Count As %
Medicine and Dentistry 12 36%
Biochemistry, Genetics and Molecular Biology 6 18%
Agricultural and Biological Sciences 3 9%
Immunology and Microbiology 1 3%
Engineering 1 3%
Other 0 0%
Unknown 10 30%

Attention Score in Context

This research output has an Altmetric Attention Score of 8. 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 29 January 2018.
All research outputs
#1,751,403
of 12,433,783 outputs
Outputs from Stem Cell Research & Therapy
#176
of 1,055 outputs
Outputs of similar age
#67,871
of 340,462 outputs
Outputs of similar age from Stem Cell Research & Therapy
#2
of 29 outputs
Altmetric has tracked 12,433,783 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,055 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.4. This one has done well, scoring higher than 83% of its peers.
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 340,462 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 79% of its contemporaries.
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 has done particularly well, scoring higher than 93% of its contemporaries.