Human Adipose-Derived Mesenchymal Stem Cell-Based Microspheres Ameliorate Atherosclerosis Progression In Vitro

Area of Science:

• Cardiovascular Biology
• Regenerative Medicine
• Biomaterials Engineering

Background:

• Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid deposition and plaque instability, leading to severe cardiovascular events.
• Adipose-derived mesenchymal stem cells (ADSCs) offer potential therapeutic benefits for AS due to their regenerative capabilities.
• Developing effective delivery systems is crucial for maximizing the therapeutic potential of stem cells in AS treatment.

Purpose of the Study:

• To fabricate and characterize stem cell repair units using human adipose-derived mesenchymal stem cells (hADSCs) encapsulated in collagen microspheres.
• To establish an in vitro model mimicking the atherosclerotic (AS) niche.
• To evaluate the therapeutic efficacy of hADSC-based microspheres in ameliorating AS progression in vitro.

Main Methods:

• Encapsulation of hADSCs in collagen microspheres to maintain viability and stemness.
• Generation of an AS progression model using hyperlipemia serum and AS cell models.
• Assessment of hADSC-microsphere efficacy by measuring inhibition of oxidative stress, apoptosis, endothelial dysfunction, inflammation, and lipid accumulation.
• Transcriptomic analysis to compare hADSC responses in AS niche versus healthy microenvironment.

Main Results:

• Encapsulation in collagen microspheres preserved hADSC viability and stemness for 14 days in vitro.
• hADSC-based microspheres significantly ameliorated AS progression by reducing oxidative stress, apoptosis, endothelial dysfunction, inflammation, and lipid accumulation.
• Transcriptomic analysis revealed distinct responses of 3D-cultured hADSCs within the AS niche compared to a healthy environment.

Conclusions:

• hADSC-based microspheres represent a promising therapeutic strategy for atherosclerosis.
• Understanding hADSC behavior in the pathological AS niche is key to optimizing stem cell therapy for cardiovascular diseases.
• This study provides novel insights into the mechanisms underlying hADSC efficacy in treating AS.