TY - JOUR
T1 - Human amniotic epithelial cell transplantation improves scar remodeling in a rabbit model of acute vocal fold injury
T2 - a pilot study
AU - Tchoukalova, Yourka D.
AU - Zacharias, Stephanie R.C.
AU - Mitchell, Natalie
AU - Madsen, Cathy
AU - Myers, Cheryl E.
AU - Gadalla, Dina
AU - Skinner, Jessica
AU - Kopaczka, Katarzyna
AU - Gramignoli, Roberto
AU - Lott, David G.
N1 - Funding Information:
Funding was provided by Mayo Clinic Regenerative Medicine; Mayo Clinic-Karolinska institute Collaborative Travel grant to RG.
Funding Information:
The authors thank Bukola Obayomi (S. M. Bukola Obayomi) who took the high mag photograph of the myocilin IF and the animal care technicians in the Mayo Clinic Natalie Schafer Animal Facility for excellent animal care.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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 × 106 hAEC in 100 µl of saline solution (hAEC) and three with 100 µl of saline solution (controls, CTR). Rabbits were euthanized 6 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 stabilization of new blood vessels indicative of accelerated and improved repair.
AB - 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 × 106 hAEC in 100 µl of saline solution (hAEC) and three with 100 µl of saline solution (controls, CTR). Rabbits were euthanized 6 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 stabilization of new blood vessels indicative of accelerated and improved repair.
KW - Amnionic epithelial cells
KW - Extracellular matrix
KW - Fibrosis
KW - Proteomics
KW - Regenerative medicine
KW - Tissue engineering
KW - Vocal fold
KW - Wound healing
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UR - http://www.scopus.com/inward/citedby.url?scp=85123746999&partnerID=8YFLogxK
U2 - 10.1186/s13287-022-02701-w
DO - 10.1186/s13287-022-02701-w
M3 - Article
C2 - 35073957
AN - SCOPUS:85123746999
SN - 1757-6512
VL - 13
JO - Stem Cell Research and Therapy
JF - Stem Cell Research and Therapy
IS - 1
M1 - 31
ER -