MiR-378a is dispensable for skeletal muscle regeneration in response to hind limb ischemia in mice

2016 ◽  
Vol 33 ◽  
pp. S77
Author(s):  
Bart Krist ◽  
Urszula Florczyk ◽  
Alicja Józkowicz ◽  
Józef Dulak
2007 ◽  
Vol 282 (43) ◽  
pp. 31453-31459 ◽  
Author(s):  
Germana Zaccagnini ◽  
Fabio Martelli ◽  
Alessandra Magenta ◽  
Chiara Cencioni ◽  
Pasquale Fasanaro ◽  
...  

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Keisuke Miyake ◽  
Shigeru Miyagawa ◽  
Takashi Shibuya ◽  
Yoshiki Sawa

Introduction: How to control inflammation, especially induction of macrophage polarization that are regulated by Extra-cellular matrix (ECM) is a prerequisite for tissue regeneration in damaged organs. In this study, we administered clustered myoblast cells with ECM framework into hind limb ischemia (HLI) model, and evaluated the change in macrophages and effect on tissue regeneration. Methods: Myoblast cells isolated from C57BL/6 mice were expanded to form cell patch with ECM framework (10 6 cells/sheet) and then fragmented and administered as cluster cells (CC group, n=6). As control groups, non-clustered single myoblast cells (SC, n=6) or saline (SA, n=6) was administered. Blood perfusion was evaluated with Laser Doppler Perfusion imaging (LDPI). Leg muscles were obtained and analyzed regarding angiogenesis, skeletal muscle regeneration, and inflammation including macrophage status. Results: LDPI showed significant improvement in CC compared with SC (P=0.001) and SA (P<0.0001) at day 28. Also, markedly augmented angiogenesis and muscle regeneration were detected in CC. Regarding inflammation, the number of CD68+ macrophages is significantly larger in CC throughout within 7 days after administration, but the character of the macrophages was quite different during time courses. Although in SC and SA macrophage polarization was rarely detected within 7 days, marked polarization was detected at day 5 only in CC. At day 5, CD11c+/CD206- (inflammatory, M1) and CD11c-/CD206+ (anti-inflammatory, M2) macrophages are discerned conspicuously (M1: 148.7±104.4/mm 2 , M2: 185.2±46.3/mm 2 , non-polarized CD11c+/CD206+: 140.9±99.4/mm 2 ), while at day 3 non-polarized macrophages were almost exclusive (M1: 2.0±2.3/mm 2 , M2: 3.1±4.0/mm 2 , CD11c+/CD206+: 410.2±90.6/mm 2 ). Consistently significant increase in IL-10 and TGF-β, that are cytokines secreted by M2 macrophages, was detected at day 5 and 7 in CC. Conclusions: Myoblast cells administration with ECM framework, which was formed during cell patch formation, augmented macrophage polarization to show anti-inflammatory effect, creating appropriate microenvironment for angiogenesis and muscle regeneration in HLI.


2008 ◽  
Vol 48 (3) ◽  
pp. 701-708 ◽  
Author(s):  
Jeanwan Kang ◽  
Hassan Albadawi ◽  
Virendra I. Patel ◽  
Thomas A. Abbruzzese ◽  
Jin-Hyung Yoo ◽  
...  

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 441
Author(s):  
Danielle E. Levitt ◽  
Alice Y. Yeh ◽  
Matthew J. Prendergast ◽  
Ronald G. Budnar, Jr. ◽  
Katherine A. Adler ◽  
...  

Alcohol use and aging are risk factors for falls requiring immobilization and leading to skeletal muscle atrophy. Skeletal muscle regeneration is integral to post-immobilization recovery. This study aimed to elucidate the effects of alcohol and ovarian hormone loss on the expression of genes implicated in muscle regeneration. Three-month-old female rats received an ovariectomy or a sham surgery, consumed an alcohol-containing or control diet for 10 weeks, were subjected to unilateral hind limb immobilization for seven days, and finally were allowed a three (3d)- or 14 (14d)-day recovery. Immobilization decreased the quadriceps weight at 3d and 14d, and alcohol decreased the quadriceps weight at 14d in the nonimmobilized hind limb (NI). At 3d, alcohol decreased gene expression of myoblast determination protein (MyoD) in the immobilized hind limb (IMM) and myocyte enhancer factor (Mef)2C and tumor necrosis factor (TNF)α in NI, and ovariectomy increased MyoD and decreased TNFα expression in NI. At 14d, alcohol increased the gene expression of Mef2C, MyoD, TNFα, and transforming growth factor (TFG)β in IMM and decreased monocyte chemoattractant protein (MCP)1 expression in NI; ovariectomy increased TNFα expression in NI, and alcohol and ovariectomy together increased Mef2C expression in NI. Despite increased TGFβ expression, there was no concomitant alcohol-mediated increase in collagen in IMM at 14d. Overall, these data indicate that alcohol dysregulated the post-immobilization alteration in the expression of genes implicated in regeneration. Whether alcohol-mediated molecular changes correspond with post-immobilization functional alterations remains to be determined.


2018 ◽  
Vol 47 (3) ◽  
pp. 1181-1192 ◽  
Author(s):  
Qingwei Zhu ◽  
Qing Li ◽  
Xin Niu ◽  
Guowei Zhang ◽  
Xiaozheng Ling ◽  
...  

Background/Aims: Our previous studies have shown that human urine-derived stem cells (USCs) have great potential as a cell source for cytotherapy and tissue engineering and that extracellular vesicles (EVs) secreted by USCs (USCs-EVs) can prevent diabetes-induced kidney injury in an animal model. The present study was designed to evaluate the effects of USCs-EVs on ischemia repair. Methods: USCs-EVs were isolated and purified by a battery of centrifugation and filtration steps. The USCs-EVs were then characterized by transmission electron microscopy, western blot and tunable resistive pulse sensing techniques. After intramuscularly transplanting USCs-EVs into an ischemic mouse hind-limb, we observed the therapeutic effects of USCs-EVs on perfusion by laser doppler perfusion imaging, angiogenesis and muscle regeneration by histology and immunohistochemistry techniques over 21 days. We subsequently tested whether USCs-EVs can induce the proliferation of a human microvascular endothelial cell line HMEC-1 and a mouse myoblast cell line C2C12 by cell counting kit 8 assay in vitro. Meanwhile, the potential growth factors in the USCs-EVs and supernatants of the USCs cultures were detected by enzyme-linked immunosorbent assay. Results: The USCs-EVs were spherical vesicles with a diameter of 30–150 nm and expressed exosomal markers, such as CD9, CD63 and Tsg101. Ischemic limb perfusion and function were markedly increased in the hind-limb ischemia (HLI) model after USCs-EVs administration. Moreover, angiogenesis and muscle regeneration levels were significantly higher in the USCs-EVs treatment group than in the PBS group. The in vitro experiments showed that USCs-EVs facilitated HMEC-1 and C2C12 cell proliferation in a dose-dependent manner. Conclusions: These results revealed for the first time that USCs-EVs efficiently attenuate severe hind-limb ischemic injury and represent a novel therapy for HLI.


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