Mesenchymal stromal cells modulate tissue repair responses within the injured vocal fold.

OBJECTIVES/HYPOTHESIS: This study aimed to determine whether local injection of human mesenchymal stromal cells (MSC) could modulate the early inflammatory response within injured vocal folds (VFs) to promote wound-healing processes.

STUDY DESIGN

Experimental xenograft model.

METHODS

VF injury was surgically induced by bilateral resection of the lamina propria of rabbits, and MSC were immediately injected into the injured area of both VFs. Animals were sacrificed on days 2, 4, and 24. Histological analyses were performed by hematoxylin and eosin, Masson's Trichrome, and elastin staining. Cell death was visualized by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and the M2 macrophage marker, CD163, detected by immunohistochemistry. Persistence of injected MSC was evaluated by fluorescent in situ hybridization (FISH). Quantitative polymerase chain reaction was performed on the contralateral VF.

RESULTS

Histological examination at days 2 and 4 indicated that MSC were able to reduce tissue inflammation, with gene expression analysis confirming a significant reduction of proinflammatory markers, interleukin (IL)-1β, and IL-8. FISH demonstrated low-level persistence of injected MSC at both time points, and TUNEL confirmed localized cell death at the injury site. Increased levels of CD163+ anti-inflammatory macrophages indicated a change in the immune milieu, supporting wound resolution. Evidence of a more organized collagen matrix suggests that MSC may enhance the production of a functional repair tissue after injury, despite their low-level persistence within the tissue.

CONCLUSIONS

This study demonstrates that MSC are able to positively modulate the early wound-healing response through resolution of the inflammatory phase and promotion of tissue repair.

LEVEL OF EVIDENCE

NA Laryngoscope, 130:E21-E29, 2020.