Gellan gum-gelatin based cardiac models support formation of cellular networks and functional cardiomyocytes

Area of Science:

• Biomaterials Science
• Cardiovascular Biology
• Stem Cell Research

Background:

• Cardiovascular diseases are a leading global cause of death.
• In vitro models are crucial for understanding heart disease mechanisms.
• 3D cell cultures with biomaterials can mimic heart tissue.

Purpose of the Study:

• To evaluate 3D co-culture systems for supporting cardiomyocyte functionality.
• To investigate the formation of vascular networks and cellular organization in cardiac models.
• To assess the potential of these models for studying cardiovascular (patho)physiology.

Main Methods:

• Cardiomyocytes (CM) were co-cultured with endothelial cells (EC) and adipose tissue-derived mesenchymal stem/stromal cells (ASC), or with ASC alone.
• Cultures were established within a hydrazide-modified gelatin and oxidized gellan gum hybrid hydrogel.
• Functional characteristics, cellular morphology, orientation, and network formation were analyzed.

Main Results:

• The gellan gum-gelatin hydrogel supported the formation of two distinct cellular networks and functional CM.
• A modest vascular network formed in the cardiovascular multiculture, alongside an extensive ASC-derived alpha smooth muscle actin-positive network.
• Induced pluripotent stem cell-derived CM (iPSC-CM) exhibited elongated morphology, partial alignment, and normal functional parameters (calcium transients, beating rates, contraction/relaxation).

Conclusions:

• The developed 3D cardiac models demonstrate the ability to support functional cardiomyocytes and form cellular networks.
• These models show promise as platforms for investigating the mechanisms of cardiovascular diseases.
• The hybrid hydrogel effectively supports complex cellular structures relevant to cardiac tissue engineering.