scholarly journals Wnt7a-Releasing Synthetic Hydrogel Enhances Local Skeletal Muscle Regeneration and Muscle Stem Cell Engraftment

Author(s):  
Woojin M. Han ◽  
Mahir Mohiuddin ◽  
Shannon E. Anderson ◽  
Andrés J. García ◽  
Young C. Jang
Cell Reports ◽  
2020 ◽  
Vol 30 (10) ◽  
pp. 3583-3595.e5 ◽  
Author(s):  
Andrea J. De Micheli ◽  
Emily J. Laurilliard ◽  
Charles L. Heinke ◽  
Hiranmayi Ravichandran ◽  
Paula Fraczek ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 744
Author(s):  
Matthew Borok ◽  
Nathalie Didier ◽  
Francesca Gattazzo ◽  
Teoman Ozturk ◽  
Aurelien Corneau ◽  
...  

Background: Skeletal muscle is one of the only mammalian tissues capable of rapid and efficient regeneration after trauma or in pathological conditions. Skeletal muscle regeneration is driven by the muscle satellite cells, the stem cell population in interaction with their niche. Upon injury, muscle fibers undergo necrosis and muscle stem cells activate, proliferate and fuse to form new myofibers. In addition to myogenic cell populations, interaction with other cell types such as inflammatory cells, mesenchymal (fibroadipogenic progenitors—FAPs, pericytes) and vascular (endothelial) lineages are important for efficient muscle repair. While the role of the distinct populations involved in skeletal muscle regeneration is well characterized, the quantitative changes in the muscle stem cell and niche during the regeneration process remain poorly characterized. Methods: We have used mass cytometry to follow the main muscle cell types (muscle stem cells, vascular, mesenchymal and immune cell lineages) during early activation and over the course of muscle regeneration at D0, D2, D5 and D7 compared with uninjured muscles. Results: Early activation induces a number of rapid changes in the proteome of multiple cell types. Following the induction of damage, we observe a drastic loss of myogenic, vascular and mesenchymal cell lineages while immune cells invade the damaged tissue to clear debris and promote muscle repair. Immune cells constitute up to 80% of the mononuclear cells 5 days post-injury. We show that muscle stem cells are quickly activated in order to form new myofibers and reconstitute the quiescent muscle stem cell pool. In addition, our study provides a quantitative analysis of the various myogenic populations during muscle repair. Conclusions: We have developed a mass cytometry panel to investigate the dynamic nature of muscle regeneration at a single-cell level. Using our panel, we have identified early changes in the proteome of stressed satellite and niche cells. We have also quantified changes in the major cell types of skeletal muscle during regeneration and analyzed myogenic transcription factor expression in satellite cells throughout this process. Our results highlight the progressive dynamic shifts in cell populations and the distinct states of muscle stem cells adopted during skeletal muscle regeneration. Our findings give a deeper understanding of the cellular and molecular aspects of muscle regeneration.


2013 ◽  
Vol 93 (1) ◽  
pp. 23-67 ◽  
Author(s):  
Hang Yin ◽  
Feodor Price ◽  
Michael A. Rudnicki

Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration.


2019 ◽  
Author(s):  
Bradley Pawlikowski ◽  
Nicole Dalla Betta ◽  
Tiffany Elston ◽  
Rebecca O’Rourke ◽  
Kenneth Jones ◽  
...  

SummaryAn individual skeletal muscle is a complex structure, composed of large contractile myofibers, connective tissue, nerve tissue, immune cells, stem cells and the vasculature. Each of these components contribute to skeletal muscle function, maintenance, regeneration, and if perturbed can potentially contribute to or cause disease that reduces muscle function. To investigate the cellular inventory of skeletal muscle we carried out single cell RNA sequencing on cells isolated from adult uninjured muscle, adult post injury muscle, and from aged uninjured muscle. Our muscle atlas provides the cellular landscape and partial transcriptome of pre-injury, post injury, and aged muscle, identifying dramatic changes in the muscle stem cell, fibroblast and immune cell populations during regeneration. Our data highlight dynamic changes occurring during muscle regeneration, identify potential extrinsic mechanisms that control muscle stem cell behavior, and underscore the inflamed state of aged uninjured muscle.


FEBS Letters ◽  
2015 ◽  
Vol 589 (11) ◽  
pp. 1257-1265 ◽  
Author(s):  
Yoshihiro Nakamura ◽  
Shigeru Miyaki ◽  
Hiroyuki Ishitobi ◽  
Sho Matsuyama ◽  
Tomoyuki Nakasa ◽  
...  

Stem Cells ◽  
2008 ◽  
Vol 26 (4) ◽  
pp. 997-1008 ◽  
Author(s):  
Viviana Moresi ◽  
Alessandro Pristerà ◽  
Bianca M. Scicchitano ◽  
Mario Molinaro ◽  
Laura Teodori ◽  
...  

2016 ◽  
Author(s):  
Floriane Lacour ◽  
Elsa Vezin ◽  
Florian Bentzinger ◽  
Marie-Claude Sincennes ◽  
Robert D. Mitchell ◽  
...  

SUMMARYTissue regeneration requires the selective activation and repression of specific signaling pathways in stem cells. As such, the Wnt signaling pathways have been shown to control stem cell fate. In many cell types, the R-Spondin (Rspo) family of secreted proteins acts as potent activators of the canonical Wnt/β-catenin pathway. Here, we identify Rspo1 as a mediator of skeletal muscle tissue repair. Firstly we show that Rspo1-null muscles do not display any abnormalities at the basal level. However deletion of Rspo1 results in global alteration of muscle regeneration kinetics following acute injury. We found that muscle stem cells lacking Rspo1 show delayed differentiation. Transcriptome analysis further demonstrated that Rspo1 is required for the activation of Wnt/β-catenin target genes in muscle cells. Furthermore, muscle cells lacking Rspo1 fuse with a higher frequency than normal cells, leading to larger myotubes containing more nuclei both in vitro and in vivo. We found the increase in muscle fusion was dependent on up-regulation of non-canonical Wnt7a/Fzd7/Rac1 signaling. We conclude that antagonistic control of canonical and non-canonical Wnt signaling pathways by Rspo1 in muscle stem cell progeny is important for restitution of normal muscle architecture during skeletal muscle regeneration.


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