MassIVE MSV000087132

Partial Public

Human Amniotic Epithelial Cell Transplantation Improves Scar Remodeling in Preclinical Model of Acute Vocal Fold Injury: A Pilot Study

Description

Objective: To gain insight into the molecular mechanisms underlying the early stages of vocal fold extracellular matrix (ECM) remodeling after a mid-membranous injury resulting from the use of human amniotic epithelial cells (hAEC), as a novel regenerative medicine cell-based therapy. Methods: Vocal folds of six female, New Zealand White rabbits were bilaterally injured. Three rabbits had immediate bilateral direct injection of 1 x 106 hAEC in 100 µl of saline solution (hAEC) and three with 100 µl of saline solution (controls, CTR). Rabbits were euthanized six weeks after injury. Proteomic analyses (in-gel trypsin protein digestion, LC-MS/MS, protein identification using Proteome Discoverer and the Uniprot Oryctolagus cuniculus (Rabbit) proteome) and histological analyses were performed. Results: hAEC treatment significantly increased the expression of ECM proteins, elastin microfibril interface-located protein 1 (EMILIN-1) and myocilin that are primarily involved in elastogenesis of blood vessels and granulation tissue. A reactome pathway analysis showed increased activity of the anchoring fibril formation by collagen I and laminin, providing mechanical stability and activation of cell signaling pathways regulating cell function. hAEC increased the abundance of keratin 1 indicating accelerated induction of the differentiation programming of the basal epithelial cells and, thereby, improved barrier function. Lastly, upregulation of Rab GDP dissociation inhibitor indicates that hAEC activate the vesicle endocytic and exocytic pathways, supporting the exosome-mediated activation of cell-matrix and cell-to-cell interactions. Conclusions: This pilot study suggests that injection of hAEC into an injured rabbit vocal fold favorably alters ECM composition creating a microenvironment that accelerates differentiation of regenerated epithelium and promotes neovascularization indicative of accelerated repair. [doi:10.25345/C5CJ73] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Vocal fold, wound healing, amnionic epithelial cells, extracellular matrix, proteomics, reepithelization, neovascularization, fibrosis

Contact

Principal Investigators:
(in alphabetical order)
David G. Lott, M.D., Mayo Clinic Arizona, USA
Submitting User: nmitche3
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