Effect of uniaxial strain on the assembly and differentiation of mammalian myogenic precursors
Author
Nielsen, Thøger
Term
4. term
Publication year
2012
Submitted on
2012-07-01
Pages
48
Abstract
Skeletmusklers myoblaster – forstadier til muskelfibre – udsættes i kroppen for mange mekaniske kræfter, som påvirker deres orientering og udvikling. I denne afhandling undersøgte vi en særlig form for mekanisk stimulation, uniaxial cyklisk træk (CTS), som er gentagne stræk i én retning. Efter vores viden er denne model ikke tidligere afprøvet på primære humane skeletmuskel-myoblaster (HSMM). Vi sammenlignede derfor HSMM med en velbeskrevet muse cellelinje, C2C12. Når HSMM og C2C12 blev udsat for CTS, stillede begge celletyper sig ensartet vinkelret på strækretningen. Markører for muskeldifferentiering (myogenin og myosin heavy chain, MHC) viste en tydelig øgning af modningen i begge celletyper, mens tidlige myogene markører (Myf-5 og MyoD1) ikke ændrede sig signifikant. Cellefusion – et skridt i dannelsen af fler-kernede muskelfibre – sås allerede dag 2 i C2C12 og dag 5 i HSMM. Desuden fandt vi sarcomer-lignende strukturer (tværstribning af aktin og myosin) i både kontrol- og CTS-grupper for begge celletyper. Samlet set viser resultaterne, at CTS både fremmer myogen differentiering og omorganiserer cytoskelettet, så cellerne orienterer sig vinkelret på strækket. HSMM reagerer dermed på mange måder som C2C12 i denne model. Disse indsigter kan være nyttige for fremtidige studier i regenerativ medicin og vævsengineering, der undersøger potentialet i primære humane myoblaster.
Skeletal muscle myoblasts—precursor cells that develop into muscle fibers—experience various mechanical forces in the body. This thesis examined a specific type of mechanical stimulation, uniaxial cyclic tensile strain (CTS), which is repeated stretching in one direction. To our knowledge, this model had not been applied to primary human skeletal muscle myoblasts (HSMM). We therefore compared HSMM with the well-studied mouse myoblast line C2C12. When exposed to CTS, both HSMM and C2C12 oriented uniformly perpendicular to the direction of stretch. Markers of muscle differentiation (myogenin and myosin heavy chain, MHC) increased in both cell types, while early myogenic markers (Myf-5 and MyoD1) did not change significantly. Cell fusion—an essential step in forming multinucleated muscle fibers—was observed by day 2 in C2C12 and by day 5 in HSMM. Sarcomere-like structures (actin and myosin cross-striations) were present in both control and CTS groups for both cell types. Overall, CTS enhanced myogenic differentiation and reorganized the cytoskeleton so that cells aligned perpendicular to the applied strain. HSMM responded in many respects similarly to C2C12 in this setup. These findings may support future work in regenerative medicine and tissue engineering that explores the potential of primary human myoblasts.
[This abstract was generated with the help of AI]
Documents