Present and future perspectives on cell sheet-based myocardial regeneration therapy

Area of Science:

• Regenerative Medicine
• Cardiovascular Biology
• Biotechnology

Background:

• Heart failure is a global health crisis with limited regenerative treatments.
• Existing surgical methods like LVAD and cell/tissue cardiomyoplasty have limitations.
• Cell sheet technology offers a novel approach to myocardial regeneration.

Purpose of the Study:

• To review advancements in cell sheet technology for heart failure treatment.
• To evaluate the efficacy of cardiomyocyte and myoblast sheets in preclinical and clinical settings.
• To explore the potential of induced pluripotent stem cell (iPS)-derived cardiomyocyte sheets.

Main Methods:

• Development and characterization of neonatal cardiomyocyte sheets.
• Establishment and in vitro/in vivo evaluation of noncontractile myoblast sheets.
• Preclinical studies in small and large animal heart failure models.
• Clinical trials using autologous myoblast sheets in ischemic and dilated cardiomyopathy patients.
• Development of iPS cell-derived cardiomyocyte sheets.

Main Results:

• Neonatal cardiomyocyte sheets demonstrated contractile ability and electrical communication with host myocardium.
• Myoblast sheets secreted cytokines (HGF, VEGF) improving cardiac function via paracrine effects (angiogenesis, antifibrosis, stem cell migration).
• Clinical trials showed LV reverse remodeling, improved symptoms, and exercise tolerance in patients.
• iPS cell-derived cardiomyocyte sheets exhibited homogeneity and proof-of-concept in animal models.

Conclusions:

• Cell sheet technology, particularly using myoblast sheets, is a promising therapeutic strategy for heart failure.
• Clinical application of autologous myoblast sheets has shown positive patient outcomes.
• iPS cell-derived cardiomyocyte sheets represent a future direction for heart regeneration.