Abstract:
: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.
journal_name
Aging (Albany NY)journal_title
Agingauthors
Tan J,Xu Y,Han F,Ye Xdoi
10.18632/aging.101790subject
Has Abstractpub_date
2019-02-06 00:00:00pages
908-920issue
3issn
1945-4589pii
101790journal_volume
11pub_type
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