Srinivasa Rao Nagubothu1, Rachael V Sugars2, Nikolce Tudzarovski2, Anton Törnqvist Andrén1, Matteo Bottai3, Lindsay C Davies1, Stellan Hertegård4,5, Katarina Le Blanc1,6. 1. Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden. 2. Department of Dental Medicine, Karolinska Institute, Stockholm, Sweden. 3. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden. 4. Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden. 5. Department of Otorhinolaryngology, Karolinska University Hospital Huddinge, Stockholm, Sweden. 6. Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Abstract
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.
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.
Authors: Eric K Tran; Yazeed Alhiyari; Kevin Juarez; Bhavani Shankara Gowda; Feng Schrader; Dipti P Sajed; Jennifer L Long Journal: Laryngoscope Investig Otolaryngol Date: 2022-09-26