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Updated: Jun 25, 2026
09:17
Optimizing Extracellular Vesicle Delivery Using a Core-Sheath 3D-Bioprinted Scaffold for Chronic Wound Management
Published on: February 28, 2025
Inflammatory Preconditioning Reprograms Mesenchymal Stromal Cell-Derived Extracellular Vesicles into Distinct
Ramiro A Villarreal-Leal1,2, Oscar S Velazquez1, Beck Burgelin3
1Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA.
Stem Cells and Development
|June 24, 2026
Summary
Preconditioning mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) with specific inflammatory cues programs distinct therapeutic properties. This research highlights tunable strategies for engineering MSC-EVs for predictable cell-free regenerative medicine applications.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Cell Biology
Background:
- Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are promising cell-free therapeutics for tissue repair.
- The functional output of MSC-EVs can be modulated by the cellular microenvironment and preconditioning strategies.
- Understanding how specific inflammatory priming affects MSC-EV properties is crucial for optimizing their therapeutic potential.
Purpose of the Study:
- To systematically evaluate how priming bone marrow-derived MSCs with interferon-gamma/tumor necrosis factor-alpha (I/T) or lipopolysaccharide (LPS) generates distinct MSC-EV populations.
- To investigate the immunomodulatory and regenerative properties of these engineered MSC-EVs in a murine wound model.
- To link EV composition to functional outcomes in vivo.
Main Methods:
- Priming bone marrow-derived MSCs with I/T or LPS.
- Subcutaneous delivery of MSC-EVs in a murine full-thickness wound model.
- Integrative analysis including biodistribution, immune response, ECM remodeling, single-cell RNA sequencing, transcriptomics, and proteomics.
Main Results:
- Both I/T-EVs and LPS-EVs supported wound contraction, but induced distinct repair trajectories.
- I/T-EVs promoted coordinated regeneration with balanced macrophage activation and organized ECM remodeling.
- LPS-EVs induced a pro-inflammatory response, accelerated contraction, and led to compensatory matrix stiffening.
- Control EVs facilitated immune resolution with limited regenerative effects.
- Proteomic analysis revealed EV cargo linked to specific signaling pathways and functional outcomes.
Conclusions:
- MSC-EV preconditioning selectively programs distinct functional states rather than uniformly enhancing efficacy.
- This selective programming allows for tunable strategies in engineering cell-free therapeutics.
- MSC-EV preconditioning offers a method for achieving predictable, context-specific therapeutic outcomes in regenerative medicine.
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