Research Paper Volume 11, Issue 3 pp 908—920
Genetical modification on adipose-derived stem cells facilitates facial nerve regeneration
- 1 Department of Plastic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
- 2 Department of Facial Plastic and Reconstructive Surgery, Eye and ENT Hospital of Fudan University, Shanghai 200031, China
received: December 29, 2018 ; accepted: January 17, 2019 ; published: February 6, 2019 ;https://doi.org/10.18632/aging.101790
How to Cite
Copyright: Tan et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Adipose-derived stem cells (ASCs) have a demonstrative therapeutic potential in aging-associated facial nerve regeneration, in which ASCs work as a source of Schwann cells therapy as an alternative to autologous nerve grafts. However, the transplantation of ASCs may induce local fibrosis, which causes inferior outcome. Here, we aimed to use genetic modification approaches to reduce the fibrogenic properties of ASCs to improve their therapeutic effects on facial nerve regeneration. Since procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) is essential for hydroxylation of lysine residues in collagen telopeptides and for collagen pyridinoline cross-link formation during fibrosis, and since we found that ASCs expressed high levels of PLOD1, we depleted PLOD1 in ASCs by expression of either a short-hair interfering RNA for PLOD1 (shPLOD1) or a microRNA-449 (miR-449), the latter of which targets PLOD1 mRNA to suppress protein translation. Transplantation of either ASCs-shPLOD1 or ASCs-miR-449 or ASCs-control to repair a 6mm-gap in rat facial nerve was compared. Either ASCs-shPLOD1 or ASCs-miR-449 exhibited a better facial nerve function. Mechanistically, ASCs-shPLOD1 or ASCs-miR-449 significantly and similarly reduced the fibrosis in the injured region, likely through suppression of reactive oxygen species (ROS) and activation of myofibroblasts.