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Related Experiment Video

Updated: Aug 9, 2025

Production and Administration of Therapeutic Mesenchymal Stem/Stromal Cell MSC Spheroids Primed in 3-D Cultures Under Xeno-free Conditions
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Production and Administration of Therapeutic Mesenchymal Stem/Stromal Cell MSC Spheroids Primed in 3-D Cultures Under Xeno-free Conditions

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Tuning the Microenvironment to Create Functionally Distinct Mesenchymal Stromal Cell Spheroids.

Victoria L Thai1,2, Diego O Candelas1, J Kent Leach3,4

  • 1Department of Biomedical Engineering, University of California, Davis, Davis, CA, 95616, USA.

Annals of Biomedical Engineering
|February 22, 2023
PubMed
Summary

Engineered mesenchymal stromal cell (MSC) spheroids were developed to enhance wound healing. These distinct spheroids, one maximizing vascular endothelial growth factor (VEGF) and the other prostaglandin E2 (PGE2), show improved therapeutic potential for tissue regeneration.

Keywords:
Design of experimentsEndothelial cellMesenchymal stromal cellPEG-4MALSpheroidsWound healing

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Cell Biology

Background:

  • Mesenchymal stromal cells (MSCs) are investigated for wound healing due to their secretome.
  • MSC spheroids enhance cell survival and secretion of factors like vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2) compared to single cells.
  • Previous methods to enhance MSC spheroid potential relied on host endothelial cell (EC) responsiveness, limiting applications in chronic wounds or large tissue deficits.

Purpose of the Study:

  • To engineer functionally distinct MSC spheroids that independently maximize VEGF or PGE2 production.
  • To incorporate ECs into engineered MSC spheroids for enhanced vessel formation.
  • To address limitations of previous MSC spheroid approaches by creating EC-independent therapeutic potential.

Main Methods:

  • A Design of Experiments (DOE) approach was used to engineer two types of MSC spheroids: VEGFmax and PGE2max.
  • VEGFmax spheroids were designed to maximize VEGF production, while PGE2max spheroids were designed to maximize PGE2 production.
  • Both spheroid types were encapsulated in protease-degradable hydrogels to model cell delivery and assess bioactivity.

Main Results:

  • VEGFmax spheroids produced 22.7-fold more VEGF, enhancing EC migration compared to PGE2max spheroids.
  • PGE2max spheroids produced 16.7-fold more PGE2, accelerating keratinocyte migration compared to VEGFmax spheroids.
  • Encapsulated VEGFmax and PGE2max spheroids showed robust spreading and enhanced metabolic activity within hydrogels.

Conclusions:

  • Engineered MSC spheroids can be functionally distinct, with tailored production of key wound-healing factors.
  • These distinct spheroid types offer tunable bioactivities, demonstrating potential for improved cell-based therapies.
  • This approach provides a new strategy for leveraging MSC therapeutic potential in tissue regeneration, overcoming limitations of EC responsiveness.