Intrapericardial injection of hydrogels with ASC and their secretome to treat dilated cardiomyopathies

Area of Science:

• Biomedical Engineering
• Cardiology
• Regenerative Medicine

Background:

• Doxorubicin-induced cardiomyopathy (DOX-IC) is a serious chemotherapy side effect causing cardiac remodeling and dysfunction.
• Current treatments for DOX-IC are limited, necessitating novel therapeutic strategies.
• Decellularized extracellular matrix (dECM) hydrogels offer a promising biomaterial for cardiac repair.

Purpose of the Study:

• To investigate the therapeutic potential of dECM hydrogels loaded with adipose tissue-derived stromal cells (ASC) and their secretome (CMed) for treating DOX-IC.
• To evaluate the impact of this novel treatment on cardiac fibrosis and hemodynamic function in a rat model.

Main Methods:

• DOX-IC was established in Wistar rats via doxorubicin injections.
• Intrapericardial administration of dECM hydrogel loaded with ASC and concentrated CMed was performed at week five.
• Cardiac fibrosis was assessed using PicroSirius Red staining, and hemodynamic parameters were measured via pressure-volume loops.

Main Results:

• ASC/CMed-loaded hydrogel treatment significantly reduced interstitial myocardial fibrosis compared to saline controls (p=0.0139).
• Ejection fraction and cardiac work efficiency showed significant improvement in the treated group (p=0.0151 and p=0.0655, respectively).
• The treatment demonstrated a positive impact on cardiac remodeling and function.

Conclusions:

• Intrapericardial injection of dECM hydrogels loaded with ASC and their secretome represents a novel therapeutic approach for DOX-IC.
• This strategy can ameliorate cardiac remodeling and improve ventricular hemodynamics.
• Further research is warranted to explore its clinical applicability.