Injectable, cryopreservable mesenchymal stromal cell-loaded microbeads for pro-angiogenic therapy:in...

Area of Science:

• Biomaterials Science
• Cell Therapy
• Tissue Engineering

Background:

• Clinical application of human mesenchymal stromal cells (hMSC) for ischemic repair is hindered by poor post-injection viability and variable paracrine function.
• Developing stable, functional, and readily available hMSC formulations is crucial for therapeutic advancement.

Purpose of the Study:

• To develop cryopreservable hMSC-loaded microbeads using biomaterial scaffolds and cell preconditioning.
• To establish a proof-of-concept for an off-the-shelf hMSC product for potential therapeutic use.

Main Methods:

• Injectable microbeads (∼500 µm) were fabricated from chitosan, chitosan-gelatin, and alginate via stirred emulsification.
• Cell viability, VEGF release (ELISA), and proangiogenic function (HUVEC wound closure) were assessed.
• Effects of freeze-thawing and celastrol preconditioning on microbeads and encapsulated hMSCs were evaluated.

Main Results:

• Chitosan-based microbeads exhibited significantly higher VEGF release (11-fold) compared to alginate.
• Chitosan-gelatin microbeads showed superior cell viability.
• Celastrol preconditioning enhanced hMSC viability (1.12-fold), VEGF release (1.40-fold), and proangiogenic function (1.2-fold).
• Cryopreserved hMSC-loaded microbeads retained mechanical properties, injectability, and paracrine function.

Conclusions:

• Chitosan-gelatin microbeads offer an advantageous scaffold for hMSC encapsulation.
• Celastrol preconditioning of hMSCs improves viability and therapeutic potential.
• The developed cryopreservable hMSC-loaded microbeads represent a promising off-the-shelf product for ischemic disease treatment, warranting further in vivo investigation.