Therapeutic effects of exon skipping and losartan on skeletal muscle of mdx mice

2014 ◽  
Vol 64 (8) ◽  
pp. 388-396 ◽  
Author(s):  
Eun-Joo Lee ◽  
Ah-Young Kim ◽  
Eun-Mi Lee ◽  
Myeong-Mi Lee ◽  
Chang-Woo Min ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exon Skipping ◽  
Mdx Mice ◽  
Therapeutic Effects

scholarly journals Anti-Fibrotic Effect of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells on Skeletal Muscle Cells, Mediated by Secretion of MMP-1

2020 ◽  
Vol 21 (17) ◽  
pp. 6269
Author(s):  
Alee Choi ◽  
Sang Eon Park ◽  
Jang Bin Jeong ◽  
Suk-joo Choi ◽  
Soo-young Oh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Wharton’S Jelly ◽  
Mdx Mice ◽  
Therapeutic Effects ◽  
Paracrine Factors ◽  
Wharton's Jelly ◽  
Muscle Fibrosis ◽  
Skeletal Muscle Fibrosis

Extracellular matrix (ECM) components play an important role in maintaining skeletal muscle function, but excessive accumulation of ECM components interferes with skeletal muscle regeneration after injury, eventually inducing fibrosis. Increased oxidative stress level caused by dystrophin deficiency is a key factor in fibrosis in Duchenne muscular dystrophy (DMD) patients. Mesenchymal stem cells (MSCs) are considered a promising therapeutic agent for various diseases involving fibrosis. In particular, the paracrine factors secreted by MSCs play an important role in the therapeutic effects of MSCs. In this study, we investigated the effects of MSCs on skeletal muscle fibrosis. In 2–5-month-old mdx mice intravenously injected with 1 × 105 Wharton’s jelly (WJ)-derived MSCs (WJ-MSCs), fibrosis intensity and accumulation of calcium/necrotic fibers were significantly decreased. To elucidate the mechanism of this effect, we verified the effect of WJ-MSCs in a hydrogen peroxide-induced fibrosis myotubes model. In addition, we demonstrated that matrix metalloproteinase-1 (MMP-1), a paracrine factor, is critical for this anti-fibrotic effect of WJ-MSCs. These findings demonstrate that WJ-MSCs exert anti-fibrotic effects against skeletal muscle fibrosis, primarily via MMP-1, indicating a novel target for the treatment of muscle diseases, such as DMD.

scholarly journals In vitro and in vivo analysis of human fibroblast reprogramming and multipotency

2015 ◽  
Vol 20 (3) ◽  
Author(s):  
Rongqing Pang ◽  
Xiangqing Zhu ◽  
Jia Geng ◽  
Yongyun Zhang ◽  
Qiang Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Fibroblasts ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Therapeutic Effects ◽  
Tail Vein ◽  
Tail Vein Injection ◽  
Activity Measurements ◽  
Human Dystrophin

AbstractMultipotent stem cells have potential therapeutic roles in the treatment of Duchenne muscular dystrophy (DMD). However, the limited access to stem cell sources restricts their clinical application. To address this issue, we established a simple in vitro epigenetic reprogramming technique in which skin fibroblasts are induced to dedifferentiate into multipotent cells. In this study, human fibroblasts were isolated from circumcised adult foreskin and were reprogrammed by co-culture for 72 h with fish oocyte extract (FOE) in serum-free medium. The cells were then observed and analyzed by immunofluorescence staining, flow cytometry and in vitro differentiation assays. Then FOE-treated human fibroblasts were transplanted by tail vein injection into irradiated mdx mice, an animal model of DMD. Two months after injection, the therapeutic effects of FOE-treated fibroblasts on mdx skeletal muscle were evaluated by serum creatine kinase (CK) activity measurements and by immunostaining and RT-PCR of human dystrophin expression. The results indicated that the reprogrammed fibroblasts expressed higher levels of the pluripotent antigen markers SSEA-4, Nanog and Oct-4, and were able to differentiate in vitro into adipogenic cells, osteoblastic cells, and myotube-like cells. Tail vein injection of FOE-treated fibroblasts into irradiated mdx mice slightly reduced serum CK activity and the percentage of centrally nucleated myofibers two months after cell transplantation. Furthermore, we confirmed human dystrophin protein and mRNA expression in mdx mouse skeletal muscle. These data demonstrated that FOE-treated fibroblasts were multipotent and could integrate into mdx mouse myofibers through the vasculature.

scholarly journals Nanopolymers improve delivery of exon skipping oligonucleotides and concomitant dystrophin expression in skeletal muscle of mdx mice

2008 ◽  
Vol 8 (1) ◽  
pp. 35 ◽  
Author(s):  
Jason H Williams ◽  
Rebecca C Schray ◽  
Shashank R Sirsi ◽  
Gordon J Lutz
Keyword(s):  
Skeletal Muscle ◽  
Exon Skipping ◽  
Mdx Mice ◽  
Dystrophin Expression

scholarly journals Therapeutic Effects of Mouse Adipose-Derived Stem Cells and Losartan in the Skeletal Muscle of Injured Mdx Mice

2015 ◽  
Vol 24 (5) ◽  
pp. 939-953 ◽  
Author(s):  
Eun-Mi Lee ◽  
Ah-Young Kim ◽  
Eun-Joo Lee ◽  
Jin-Kyu Park ◽  
Myeong-Mi Lee ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Mdx Mice ◽  
Therapeutic Effects ◽  
Adipose Derived Stem Cells

scholarly journals Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models

2019 ◽  
Vol 8 ◽  
pp. 204800401987958
Author(s):  
HR Spaulding ◽  
C Ballmann ◽  
JC Quindry ◽  
MB Hudson ◽  
JT Selsby
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Progression ◽  
Gene Mutations ◽  
Dystrophin Gene ◽  
Mdx Mice ◽  
Dystrophin Deficiency ◽  
Muscle Wasting Disease ◽  
Dystrophin Protein

Background Duchenne muscular dystrophy is a muscle wasting disease caused by dystrophin gene mutations resulting in dysfunctional dystrophin protein. Autophagy, a proteolytic process, is impaired in dystrophic skeletal muscle though little is known about the effect of dystrophin deficiency on autophagy in cardiac muscle. We hypothesized that with disease progression autophagy would become increasingly dysfunctional based upon indirect autophagic markers. Methods Markers of autophagy were measured by western blot in 7-week-old and 17-month-old control (C57) and dystrophic (mdx) hearts. Results Counter to our hypothesis, markers of autophagy were similar between groups. Given these surprising results, two independent experiments were conducted using 14-month-old mdx mice or 10-month-old mdx/Utrn± mice, a more severe model of Duchenne muscular dystrophy. Data from these animals suggest increased autophagosome degradation. Conclusion Together these data suggest that autophagy is not impaired in the dystrophic myocardium as it is in dystrophic skeletal muscle and that disease progression and related injury is independent of autophagic dysfunction.

O.10 Effect of combined treatment with soluble activin receptor IIB and AAV-U7-mediated dystrophin exon skipping on muscle function in mdx mice

2011 ◽  
Vol 21 (9-10) ◽  
pp. 703
Author(s):  
W.M.H. Hoogaars ◽  
E. Mouisel ◽  
K. Relizani ◽  
A. Pasternack ◽  
C. Hourde ◽  
...  
Keyword(s):  
Muscle Function ◽  
Combined Treatment ◽  
Exon Skipping ◽  
Mdx Mice ◽  
Activin Receptor ◽  
Activin Receptor Iib ◽  
O 10

Aquaporin‐4 deficiency in skeletal muscle and brain of dystrophic mdx mice

2001 ◽  
Vol 15 (1) ◽  
pp. 90-98 ◽  
Author(s):  
ANTONIO FRIGERI ◽  
GRAZIA PAOLA NICCHIA ◽  
BEATRICE NICO ◽  
FABIO QUONDAMATTEO ◽  
RAINER HERKEN ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Aquaporin 4 ◽  
Mdx Mice

scholarly journals Early metabolic changes measured by 1H MRS in healthy and dystrophic muscle after injury

2012 ◽  
Vol 113 (5) ◽  
pp. 808-816 ◽  
Author(s):  
Su Xu ◽  
Stephen J. P. Pratt ◽  
Espen E. Spangenburg ◽  
Richard M. Lovering
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Tibialis Anterior Muscle ◽  
Metabolic Changes ◽  
Mdx Mice ◽  
Resonance Spectroscopy ◽  
Dystrophic Muscle ◽  
1H Mrs ◽  
Skeletal Muscle Injury

Skeletal muscle injury is often assessed by clinical findings (history, pain, tenderness, strength loss), by imaging, or by invasive techniques. The purpose of this work was to determine if in vivo proton magnetic resonance spectroscopy (1H MRS) could reveal metabolic changes in murine skeletal muscle after contraction-induced injury. We compared findings in the tibialis anterior muscle from both healthy wild-type (WT) muscles (C57BL/10 mice) and dystrophic ( mdx mice) muscles (an animal model for human Duchenne muscular dystrophy) before and after contraction-induced injury. A mild in vivo eccentric injury protocol was used due to the high susceptibility of mdx muscles to injury. As expected, mdx mice sustained a greater loss of force (81%) after injury compared with WT (42%). In the uninjured muscles, choline (Cho) levels were 47% lower in the mdx muscles compared with WT muscles. In mdx mice, taurine levels decreased 17%, and Cho levels increased 25% in injured muscles compared with uninjured mdx muscles. Intramyocellular lipids and total muscle lipid levels increased significantly after injury but only in WT. The increase in lipid was confirmed using a permeable lipophilic fluorescence dye. In summary, loss of torque after injury was associated with alterations in muscle metabolite levels that may contribute to the overall injury response in mdx mice. These results show that it is possible to obtain meaningful in vivo 1H MRS regarding skeletal muscle injury.

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