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Developing an animal model of Dupuytren’s disease by orthotopic transplantation of human fibroblasts into athymic rat

Overview of attention for article published in BMC Musculoskeletal Disorders, June 2015
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Title
Developing an animal model of Dupuytren’s disease by orthotopic transplantation of human fibroblasts into athymic rat
Published in
BMC Musculoskeletal Disorders, June 2015
DOI 10.1186/s12891-015-0597-z
Pubmed ID
Authors

Latha Satish, Bradley Palmer, Fang Liu, Loukia Papatheodorou, Lora Rigatti, Mark E. Baratz, Sandeep Kathju

Abstract

Dupuytren's disease (DD) is a slow, progressive fibroproliferative disorder affecting the palms of the hands. The disease is characterized by the formation of collagen rich- cords which gradually shorten by the action of myofibroblasts resulting in finger contractures. It is a disease that is confined to humans, and a major limiting factor in investigating this disorder has been the lack of a faithful animal model that can recapitulate its distinct biology. The aim of this study was to develop such a model by determining if Dupuytren's disease (DD)- and control carpal tunnel (CT)-derived fibroblasts could survive in the forepaw of the nude rats and continue to exhibit the distinct characteristics they display in in vitro cultures. 1x10(7) fluorescently labeled DD- and CT-derived fibroblasts were transplanted into the left and right forepaws of nude rats respectively. Cells were tracked at regular intervals for a period of two months by quantifying emitted fluorescent signal using an IVIS imaging system. After a period of 62 days rat forepaw connective tissues were harvested for histology and total RNA was isolated. Human-specific probes were used to perform real time RT-PCR assays to examine the expression patterns of gene products associated with fibrosis in DD. Rat forepaw skin was also harvested to serve as an internal control. Both CT- and DD-derived fibroblasts survived for a period of 62 days, but DD-derived cells showed a significantly greater level of persistent fluorescent signal at the end of this time than did CT-derived cells. mRNA expression levels of α-smooth muscle actin (α-SMA), type I- and type III- collagens were all significantly elevated in the forepaw receiving DD cord-derived fibroblasts in comparison to CT-derived fibroblasts. Masson's trichrome stain confirmed increased collagen deposition in the forepaw that was injected with DD cord-derived fibroblasts. For the first time we describe an animal model for Dupuytren's disease at the orthotopic anatomical location. We further show that gene expression differences between control (CT) and diseased (DD) derived fibroblasts persist when these cells are transplanted to the forepaw of the nude rat. These preliminary findings indicate that, with further refinements, this animal model holds promise as a baseline for investigating novel therapeutic regimens to determine an effective strategy in treating DD.

Mendeley readers

The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 20 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 25%
Researcher 4 20%
Other 3 15%
Student > Bachelor 2 10%
Student > Master 1 5%
Other 2 10%
Unknown 3 15%
Readers by discipline Count As %
Medicine and Dentistry 7 35%
Agricultural and Biological Sciences 3 15%
Engineering 2 10%
Biochemistry, Genetics and Molecular Biology 2 10%
Earth and Planetary Sciences 1 5%
Other 1 5%
Unknown 4 20%

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 08 July 2015.
All research outputs
#4,437,008
of 5,329,056 outputs
Outputs from BMC Musculoskeletal Disorders
#1,600
of 1,758 outputs
Outputs of similar age
#150,753
of 187,836 outputs
Outputs of similar age from BMC Musculoskeletal Disorders
#50
of 55 outputs
Altmetric has tracked 5,329,056 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 1,758 research outputs from this source. They receive a mean Attention Score of 4.3. 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 187,836 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 55 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.