Genetically engineered myoblast sheet for therapeutic angiogenesis.

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Tissue Engineering

Background:

• Peripheral arterial disease (PAD) is a serious complication of atherosclerosis, leading to ischemic events in extremities.
• Current cell therapy for PAD faces challenges due to poor transplanted cell survival and engraftment.
• Therapeutic angiogenesis aims to restore blood flow in ischemic tissues.

Purpose of the Study:

• To develop an improved cell therapy for peripheral ischemia using genetically engineered cell sheets.
• To enhance cell survival and angiogenic potential for treating peripheral arterial disease.
• To evaluate the efficacy of VEGF-transfected C2C12 myoblast sheets in an ischemic limb model.

Main Methods:

• C2C12 myoblast sheets were cultured on a Tetronic-tyramine (Tet-TA)-RGD hydrogel.
• Myoblast sheets were transfected with vascular endothelial growth factor (VEGF) plasmids using poly(β-amino ester) nanoparticles.
• In vitro capillary formation assays and in vivo transplantation in an ischemic limb model were performed.

Main Results:

• Engineered cell sheets demonstrated increased VEGF expression and secretion.
• VEGF-transfected sheets significantly enhanced in vitro angiogenesis.
• Transplantation of modified cell sheets promoted neovascularization, reduced muscle damage, and prevented ischemic limb loss in vivo.

Conclusions:

• Combining cell sheet engineering with genetic modification offers a promising strategy for therapeutic angiogenesis.
• This approach overcomes limitations of traditional cell therapy for peripheral ischemia.
• The developed VEGF-transfected C2C12 cell sheets show potential for treating peripheral arterial disease.