Development of a skeletal muscle sheet with direct reprogramming-induced myoblasts on a nanogel-cross-linked porous freeze-dried gel scaffold in a mouse gastroschisis model
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In brief
In brief
Researchers developed a novel skeletal muscle sheet using directly reprogrammed myoblasts on a nanogel scaffold to treat gastroschisis in a mouse model. The nanogel-based approach showed superior muscle cell differentiation compared to traditional Matrigel, with cells forming multinucleated muscle fibers expressing key muscle markers. This technique offers potential for autologous tissue-based reconstruction of abdominal wall defects in congenital conditions.
- Direct reprogramming of fibroblasts into myoblasts (dMBs) via MYOD1/MYCL transfection enables autologous skeletal muscle regeneration.
- NanoClip-FD gel scaffold outperformed Matrigel, producing multinucleated muscle cells expressing desmin and myogenin at 14 days.
- Porous nanogel structure facilitates oxygen/nutrient delivery, critical for cell differentiation and engraftment in tissue engineering.
- Biosheet-based skeletal muscle constructs show promise for gastroschisis repair using patient-derived cells and tissues.
- Combining direct cellular reprogramming with nanogel scaffolds offers a novel approach to regenerative abdominal wall reconstruction.
Written by the GCMD Library team from the article.
Abstract
Purpose
In this study, we attempted to create skeletal muscle sheets made of directly converted myoblasts (dMBs) with a nanogel scaffold on a biosheet using a mouse gastroschisis model.
Methods
dMBs were prepared by the co-transfection of MYOD1 and MYCL into human fibroblasts. Silicon tubes were implanted under the skin of NOG/SCID mice, and biosheets were formed. The nanogel was a nanoscale hydrogel based on cholesterol-modified pullulan, and a NanoClip-FD gel was prepared by freeze-drying the nanogel. 7 mm in length was created in the abdominal wall of NOG/SCID mice as a mouse gastroschisis model. Matrigel or NanoCliP-FD gel seeded with dMBs was placed on the biosheet and implanted on the model mice.
Results
Fourteen days after surgery, dMBs with Matrigel showed a small amount of coarse aggregations of muscle-like cells. In contrast, dMBs with NanoCliP-FD gel showed multinucleated muscle-like cells, which were expressed as desmin and myogenin by fluorescent immunostaining.
Conclusion
Nanogels have a porous structure and are useful as scaffolds for tissue regeneration by supplying oxygen and nutrients supply to the cells. Combining dMBs and nanogels on the biosheets resulted in the differentiation and engraftment of skeletal muscle, suggesting the possibility of developing skeletal muscle sheets derived from autologous cells and tissues.