4.6 Article

Oral Progenitor Cell Line-Derived Small Extracellular Vesicles as a Treatment for Preferential Wound Healing Outcome

Journal

STEM CELLS TRANSLATIONAL MEDICINE
Volume 11, Issue 8, Pages 861-875

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/stcltm/szac037

Keywords

stem cells; oral mucosa; immortalization; small extracellular; vesicles; regenerative medicine; scarless wound healing; scarring

Funding

  1. Cardiff University
  2. Cardiff Institute of Tissue Engineering and Repair
  3. Dunhill Medical Trust [RPGF1902\133]

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Researchers have developed an immortalized oral progenitor cell line that produces small extracellular vesicles (sEVs) capable of promoting wound healing and inhibiting scar formation. These oral sEVs show higher potency and functionality compared to sEVs derived from other cell sources, making them a preferred product for therapeutic development. This study provides a new option for non-scarring wound healing in clinical settings.
Knight et al produced an immortalized oral progenitor cell line that secretes small extracellular vesicles (sEVs) which stimulate positive wound healing responses (increased fibroblast migration/proliferation) as well as deliver potential anti-scarring properties (inhibition of myofibroblast formation). OMLP-PC(L)sEVs demonstrate an increased potency/functionality over more commonly described mesenchymal stromal cell-derived sEVs, presenting oral sEVs as a preferential product for the therapeutic development. Scar formation during wound repair can be devastating for affected individuals. Our group previously documented the therapeutic potential of novel progenitor cell populations from the non-scarring buccal mucosa. These Oral Mucosa Lamina Propria-Progenitor Cells (OMLP-PCs) are multipotent, immunosuppressive, and antibacterial. Small extracellular vesicles (sEVs) may play important roles in stem cell-mediated repair in varied settings; hence, we investigated sEVs from this source for wound repair. We created an hTERT immortalized OMLP-PC line (OMLP-PCL) and confirmed retention of morphology, lineage plasticity, surface markers, and functional properties. sEVs isolated from OMLP-PCL were analyzed by nanoparticle tracking analysis, Cryo-EM and flow cytometry. Compared to bone marrow-derived mesenchymal stromal cells (BM-MSC) sEVs, OMLP-PCL sEVs were more potent at driving wound healing functions, including cell proliferation and wound repopulation and downregulated myofibroblast formation. A reduced scarring potential was further demonstrated in a preclinical in vivo model. Manipulation of OMLP-PCL sEVs may provide novel options for non-scarring wound healing in clinical settings.

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