Bioengineered human skeletal muscle capable of functional regeneration.

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Skeletal Muscle Physiology

Background:

• Skeletal muscle (SkM) regeneration is crucial for recovery from injury.
• Severe injuries can lead to non-regenerative defects, causing functional loss and chronic pain.
• Current bioengineered SkM models often fail to replicate human regenerative physiology.

Purpose of the Study:

• To develop an engineered human SkM capable of functional regeneration.
• To overcome limitations in cell number and mitogenicity of human myogenic precursor cells (hMPCs).
• To create a pre-clinical testing model for understanding SkM regenerative physiology.

Main Methods:

• Utilized magnetic-activated cell sorting (MACS) for CD56+ hMPCs to enhance cell expansion.
• Supplemented culture media with fibroblast growth factor 2 (FGF-2) and B-27 to improve myogenesis and force generation.
• Induced injury in engineered SkM using barium chloride (BaCl2) to study regeneration.

Main Results:

• Optimized hMPC expansion and improved myogenesis and mature tissue force generation.
• Engineered SkM successfully regenerated after BaCl2-induced injury, with functional recovery observed.
• Observed increased MyoD+ cells during proliferation and expansion of Pax7+ cells, indicating regenerative potential similar to satellite cell self-renewal.

Conclusions:

• Developed an engineered human SkM model that exhibits functional regeneration post-injury.
• The open-source system provides a valuable tool for pre-clinical testing and advancing regenerative physiology knowledge.
• This model closely mimics functional human regenerative physiology, offering new avenues for treating SkM defects.