Cellular therapy for myocardial ischemia using a temperature-responsive biodegradable injectable polymer system with...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Stem Cell Biology

Background:

• Adipose-derived stem cells (AdSCs) are promising for regenerative medicine due to their differentiation potential and paracrine factor secretion.
• Effective delivery of AdSCs to ischemic tissues, like the heart, is crucial for therapeutic success.
• Existing injectable polymer systems require improvement for sustained AdSC viability and function.

Purpose of the Study:

• To evaluate an injectable polymer (IP) hydrogel system for enhanced adipose-derived stem cell (AdSC) delivery in treating ischemic heart conditions.
• To compare the efficacy of physical versus chemical IP hydrogels in supporting AdSC viability, function, and retention.
• To assess the therapeutic potential of the IP-mediated AdSC delivery system in a mouse model of myocardial infarction.

Main Methods:

• AdSCs were cultured within physical and chemical injectable polymer (IP) hydrogels composed of modified poly(ɛ-caprolactone-co-glycolic acid)-poly(ethylene glycol) (tri-PCG).
• Cell viability, mRNA expression (RT-PCR), and cytokine secretion (ELISA) of AdSCs within hydrogels were analyzed.
• AdSCs encapsulated in chemical IP hydrogels were injected into a mouse model of ischemic heart, and cell retention and cardiac function recovery were evaluated.

Main Results:

• Both physical and chemical IP hydrogels supported AdSC viability.
• AdSCs cultured in the chemical IP hydrogel exhibited higher mRNA expression and vascular endothelial growth factor secretion compared to the physical hydrogel.
• In vivo studies showed enhanced AdSC retention at the injection site and improved cardiac function recovery in mice treated with AdSCs in the chemical IP hydrogel.

Conclusions:

• The developed injectable polymer system, particularly the chemical hydrogel, effectively delivers adipose-derived stem cells (AdSCs) for myocardial infarction treatment.
• The chemical IP hydrogel enhances AdSC retention and promotes therapeutic paracrine factor secretion, leading to improved cardiac function.
• This IP-mediated AdSC delivery system shows significant promise for regenerative medicine applications in treating ischemic heart disease.