Adult human cardiac stem cell supplementation effectively increases contractile function and maturation in human...

Area of Science:

• Cardiovascular Biology
• Regenerative Medicine
• Stem Cell Therapy

Background:

• Stem cell therapy shows promise for heart failure but faces challenges in human translation.
• Investigating human cardiac stem cells (hCSCs) in a human engineered cardiac tissue (hECT) model bridges the species gap.

Purpose of the Study:

• To evaluate the impact of hCSC supplementation on the contractile function of hECTs.
• To assess the effects of hCSCs on cardiac tissue maturation and electrophysiology.

Main Methods:

• hECTs were fabricated using human induced pluripotent stem cell-derived cardiomyocytes (hCMs) with or without hCSCs (9:1 ratio).
• Functional assessments included contractility and electrophysiological measurements under spontaneous and paced conditions.
• Gene expression analysis was performed using a Nanostring assay with a cardiac-targeted panel.

Main Results:

• hCSC-supplemented hECTs exhibited significantly higher developed force and stress compared to controls.
• Enhanced contractility persisted through days 8 and 10, with no adverse effects on beat rate or variability.
• Gene analysis revealed increased expression of markers associated with cardiac maturation (e.g., MYH7/MHY6, MYL2/MYL7, TNNI3/TNNI1).

Conclusions:

• hCSC supplementation significantly improves in vitro human cardiac tissue contractility.
• This improvement is associated with enhanced cardiac maturation markers and no proarrhythmic effects.
• These findings highlight the potential of hCSCs for functional improvement of the human myocardium.