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Updated: Nov 8, 2025
Direct Reprogramming of Human Fibroblasts into Myoblasts to Investigate Therapies for Neuromuscular Disorders
Published on: April 3, 2021
Direct Reprogramming of Human Fibroblasts into Myoblasts to Investigate Therapies for Neuromuscular Disorders
Camila F Almeida1, Emma C Frair1, Nianyuan Huang1
1Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital.
Abstract:
Investigations into both the pathophysiology and therapeutic targets in muscular dystrophies have been hampered by the limited proliferative capacity of human myoblasts. Several mouse models have been created but they either do not truly represent the human physiopathology of the disease or are not representative of the broad spectrum of mutations found in humans. The immortalization of human primary myoblasts is an alternative to this limitation; however, it is still dependent on muscle biopsies, which are invasive and not easily available. In contrast, skin biopsies are easier to obtain and less invasive to patients. Fibroblasts derived from skin biopsies can be immortalized and transdifferentiated into myoblasts, providing a source of cells with excellent myogenic potential. Here, we describe a fast and direct reprogramming method of fibroblast into a myogenic lineage. Fibroblasts are transduced with two lentiviruses: hTERT to immortalize the primary culture and a tet-inducible MYOD, which upon the addition of doxycycline, induces the conversion of fibroblasts into myoblasts and then mature myotubes, which express late differentiation markers. This quick transdifferentiation protocol represents a powerful tool to investigate pathological mechanisms and to investigate innovative gene-based or pharmacological biotherapies for neuromuscular disorders.
Insights
Researchers developed a fast reprogramming method to convert skin fibroblasts into myoblasts, offering a new cell source for studying muscular dystrophies and developing therapies.
Area of Science:
- Biotechnology
- Cell Biology
- Regenerative Medicine
Background:
- Human myoblast proliferation limits muscular dystrophy research.
- Existing mouse models and myoblast sources have significant limitations.
- Skin biopsies are less invasive than muscle biopsies for cell acquisition.
Purpose of the Study:
- To establish a rapid and direct method for reprogramming fibroblasts into myogenic cells.
- To overcome limitations in cell source availability for muscular dystrophy research.
- To create a versatile platform for investigating disease mechanisms and therapies.
Main Methods:
- Fibroblasts were transduced with lentiviruses for immortalization (hTERT) and inducible MYOD expression.
- Doxycycline addition triggered the tet-inducible MYOD to reprogram fibroblasts.
- Reprogrammed cells were assessed for myoblast and myotube differentiation markers.
Main Results:
- A fast and direct fibroblast-to-myoblast reprogramming protocol was established.
- Transdifferentiated cells exhibited characteristics of mature myotubes expressing late markers.
- The method provides a renewable and accessible cell source with myogenic potential.
Conclusions:
- This transdifferentiation protocol offers a powerful tool for muscular dystrophy research.
- It facilitates the investigation of pathological mechanisms in neuromuscular disorders.
- The method supports the development of novel gene-based and pharmacological biotherapies.
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