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Engineering Skeletal Muscle Tissues from Murine Myoblast Progenitor Cells and Application of Electrical Stimulation
Published on: March 19, 2013
Soluble miniagrin enhances contractile function of engineered skeletal muscle
1Department of Anesthesia and Medicine and Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Summary
Neural agrin enhances engineered muscle function by increasing force and improving acetylcholine receptor clustering. This suggests agrin can directly boost contractile performance in aneural muscle tissues.
Area of Science:
- Biomedical Engineering
- Muscle Physiology
- Neurobiology
Background:
- Neural agrin is crucial for skeletal muscle innervation and maturation.
- The impact of neural agrin on aneural engineered muscle contractile function is not well understood.
Purpose of the Study:
- To investigate the effects of soluble recombinant mini-agrin on the contractile function of engineered skeletal muscle tissues.
- To elucidate the mechanisms underlying agrin's effects on muscle constructs.
Main Methods:
- Neonatal rat skeletal myoblasts were cultured into 3D engineered muscle tissue constructs.
- Constructs were treated with mini-agrin and assessed via histological, biochemical, and functional assays.
- Acetylcholine (ACh) levels were manipulated using α-NETA to study agrin's effects in different contexts.
Main Results:
- Mini-agrin treatment increased twitch and tetanus force amplitude by up to 1.7-fold.
- Agrin up-regulated dystrophin gene expression (2.3-fold) and enhanced acetylcholine receptor (AChR) clustering.
- Agrin improved AChR clustering and twitch force even when endogenous ACh was suppressed, but did not improve Ca(2+) handling.
Conclusions:
- Neural agrin can directly enhance the contractile function of aneural engineered muscle.
- Agrin's effects involve mechanisms beyond endogenous acetylcholine signaling.
- Agrin may promote the integration of engineered muscle constructs in vivo through its synaptogenic function.
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