The influence of extracellular matrix derived from skeletal muscle tissue on the proliferation and differentiation of myogenic progenitor cells ex vivo

Biomaterials ◽  
2009 ◽  
Vol 30 (12) ◽  
pp. 2393-2399 ◽  
Author(s):  
Matthew M. Stern ◽  
Regina L. Myers ◽  
Nevin Hammam ◽  
Kathryn A. Stern ◽  
Daniel Eberli ◽  
...  
2021 ◽  
Author(s):  
Inseon Kim ◽  
Adhideb Ghosh ◽  
Nicola Bundschuh ◽  
Laura Hinte ◽  
Ferdinand von Meyenn ◽  
...  

Transient MyoD overexpression in concert with small molecules treatment reprograms mouse fibroblasts into induced myogenic progenitor cells (iMPCs). However, the molecular landscape and mechanisms orchestrating this cellular conversion remain unknown. Here, we undertook an integrative multi-omics approach to delineate the process of iMPC reprogramming in comparison to myogenic transdifferentiation mediated solely by MyoD. Utilizing transcriptomics, proteomics and genome-wide chromatin accessibility assays, we unravel distinct molecular trajectories which govern the two processes. Notably, iMPC reprogramming is characterized by gradual upregulation of stem and progenitor cell markers, unique signaling pathways, chromatin remodelers and cell cycle regulators which manifest via rewiring of the chromatin in core myogenic promoters. Furthermore, we determine that only iMPC reprogramming is mediated by Notch pathway activation, which is indispensable for iMPC formation and self-renewal. Collectively, this study charts divergent molecular blueprints for myogenic transdifferentiation or reprogramming and underpins the heightened capacity of iMPCs in capturing myogenesis ex vivo.


Nanomaterials ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1781 ◽  
Author(s):  
Sara Politi ◽  
Felicia Carotenuto ◽  
Antonio Rinaldi ◽  
Paolo Di Nardo ◽  
Vittorio Manzari ◽  
...  

The development of smart and intelligent regenerative biomaterials for skeletal muscle tissue engineering is an ongoing challenge, owing to the requirement of achieving biomimetic systems able to communicate biological signals and thus promote optimal tissue regeneration. Electrospinning is a well-known technique to produce fibers that mimic the three dimensional microstructural arrangements, down to nanoscale and the properties of the extracellular matrix fibers. Natural and synthetic polymers are used in the electrospinning process; moreover, a blend of them provides composite materials that have demonstrated the potential advantage of supporting cell function and adhesion. Recently, the decellularized extracellular matrix (dECM), which is the noncellular component of tissue that retains relevant biological cues for cells, has been evaluated as a starting biomaterial to realize composite electrospun constructs. The properties of the electrospun systems can be further improved with innovative procedures of functionalization with biomolecules. Among the various approaches, great attention is devoted to the “click” concept in constructing a bioactive system, due to the modularity, orthogonality, and simplicity features of the “click” reactions. In this paper, we first provide an overview of current approaches that can be used to obtain biofunctional composite electrospun biomaterials. Finally, we propose a design of composite electrospun biomaterials suitable for skeletal muscle tissue regeneration.


2006 ◽  
Vol 290 (2) ◽  
pp. C379-C387 ◽  
Author(s):  
Thomas J. Hawke ◽  
Shane B. Kanatous ◽  
Cindy M. Martin ◽  
Sean C. Goetsch ◽  
Daniel J. Garry

The successful use of myogenic progenitor cells for therapeutic applications requires an understanding of the intrinsic and extrinsic cues involved in their regulation. Herein we demonstrate the expression pattern and transcriptional regulation of Rad, a prototypical member of a family of novel Ras-related GTPases, during mammalian development and skeletal muscle regeneration. Rad was identified using microarray analysis, which revealed robust upregulation of its expression during skeletal muscle regeneration. Our current findings demonstrate negligible Rad expression with resting adult skeletal muscle; however, after muscle injury, Rad is expressed within the myogenic progenitor cell population. Rad expression is significantly increased and localized to the myogenic progenitor cell population during the early phases of regeneration and within the newly regenerated myofibers during the later phases of regeneration. Immunohistochemical analysis demonstrated that Rad and MyoD are coexpressed within the myogenic progenitor cell population of regenerating skeletal muscle. This expression profile of Rad during skeletal muscle regeneration is consistent with the proposed roles for Rad in the inhibition of L-type Ca2+channel activity and the inhibition of Rho/RhoA kinase activity. We also have demonstrated that known myogenic transcription factors (MEF2, MyoD, and Myf-5) can increase the transcriptional activity of the Rad promoter and that this ability is significantly enhanced by the presence of the Ca2+-dependent phosphatase calcineurin. Furthermore, this enhanced transcriptional activity appears to be dependent on the presence of a conserved NFAT binding motif within the Rad promoter. Taken together, these data define Rad as a novel factor within the myogenic progenitor cells of skeletal muscle and identify key regulators of its transcriptional activity.


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