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Myoblast-conditioned media improve regeneration and revascularization of ischemic muscles in diabetic mice

Overview of attention for article published in Stem Cell Research & Therapy, April 2015
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Title
Myoblast-conditioned media improve regeneration and revascularization of ischemic muscles in diabetic mice
Published in
Stem Cell Research & Therapy, April 2015
DOI 10.1186/s13287-015-0063-8
Pubmed ID
Authors

Magdalena Kozakowska, Jerzy Kotlinowski, Anna Grochot-Przeczek, Maciej Ciesla, Bartosz Pilecki, Rafal Derlacz, Jozef Dulak, Alicja Jozkowicz

Abstract

Diabetes is associated with reduced expression of heme oxygenase-1 (HO-1), a heme-degrading enzyme of cytoprotective and proangiogenic properties. In myoblasts and satellite cells (mSCs) HO-1 improves survival, proliferation and production of proangiogenic growth factors. Induction of HO-1 in injured tissues facilitates neovascularization, the process impaired in diabetes. We aimed to examine whether conditioned media from the HO-1 overexpressing myoblast cell line can improve a blood-flow recovery in ischemic muscles of diabetic mice. Analysis of myogenic markers was performed at mRNA level in primary mSCs, isolated by a pre-plate technique from diabetic db/db and normoglycemic wild type mice, and then cultured under growth or differentiation conditions. Hind limb ischemia was performed by femoral artery ligation in db/db mice and blood recovery was monitored by Laser Doppler measurements. Mice were treated with a single intramuscular injection of conditioned media harvested from wild type C2C12 myoblast cell line, C2C12 cells stably transduced with HO-1 cDNA or with unconditioned media. Expression of HO-1 was lower in mSCs isolated from muscles of diabetic db/db mice when compared to their wild type counterparts, what was accompanied by increased levels of Myf5 or CXCR4, and decreased Mef2 or Pax7. Such cells displayed also diminished differentiation potential when cultured in vitro, as shown by less effective formation of myotubes and reduced expression of myogenic markers (myoD, myogenin, and myosin). Blood flow recovery after induction of severe hind limb ischemia was delayed in db/db mice compared to that in normoglycemic individuals. To improve muscle regeneration after ischemia, conditioned media collected from differentiating C2C12 cells (control and HO-1 overexpressing) were injected into hind limbs of diabetic mice. Analysis of blood flow revealed that media from HO-1 overexpressing cells accelerated blood-flow recovery, while immunohistochemical staining assessment of vessels density in injected muscle confirmed increased angiogenesis. The effect might be mediated by SDF-1α proangiogenic factor, as its secretion is elevated in HO-1 overexpressing cells. In conclusion, paracrine stimulation of angiogenesis in ischemic skeletal muscle using conditioned media may be a safe approach exploiting protective and proangiogenic properties of HO-1 in diabetes.

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Mendeley readers

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 %
United States 1 3%
Unknown 32 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 9 27%
Student > Ph. D. Student 7 21%
Student > Master 4 12%
Student > Postgraduate 2 6%
Student > Bachelor 2 6%
Other 4 12%
Unknown 5 15%
Readers by discipline Count As %
Medicine and Dentistry 7 21%
Biochemistry, Genetics and Molecular Biology 6 18%
Agricultural and Biological Sciences 5 15%
Neuroscience 2 6%
Nursing and Health Professions 1 3%
Other 4 12%
Unknown 8 24%
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 05 February 2016.
All research outputs
#20,273,512
of 22,805,349 outputs
Outputs from Stem Cell Research & Therapy
#2,045
of 2,418 outputs
Outputs of similar age
#223,725
of 264,601 outputs
Outputs of similar age from Stem Cell Research & Therapy
#67
of 73 outputs
Altmetric has tracked 22,805,349 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 2,418 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 264,601 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 73 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.