Faculty Collaboration Database

Increasing Nerve Autograft Length Increases Senescence and Reduces Regeneration. Plast Reconstr Surg 2018 Oct;142(4):952-961

Date

07/12/2018

Pubmed ID

29994844

Pubmed Central ID

PMC6156921

DOI

10.1097/PRS.0000000000004759

Scopus ID

2-s2.0-85056835765 (requires institutional sign-in at Scopus site)   50 Citations

Abstract

BACKGROUND: Nerve grafting with an autograft is considered the gold standard. However, the functional outcomes of long (>3 cm) nerve autografting are often poor. The authors hypothesized that a factor contributing to these outcomes is the graft microenvironment, where long compared to short autografts support axon regeneration to different extents.

METHODS: A rat sciatic nerve defect model was used to compare regeneration in short (2 cm) and long (6 cm) isografts. Axon regeneration and cell populations within grafts were assessed using histology, retrograde labeling of neurons regenerating axons, immunohistochemistry, quantitative reverse transcriptase polymerase chain reaction, and electron microscopy at 4 and/or 8 weeks.

RESULTS: At 8 weeks, for distances of both 1 and 2 cm from the proximal coaptation (equivalent regenerative distance), long isografts had reduced numbers of regenerated fibers compared with short isografts. Similarly, the number of motoneurons regenerating axons was reduced in the presence of long isografts compared with short isografts. Considering the regenerative microenvironments between short and long isografts, cell densities and general populations within both short and long isografts were similar. However, long isografts had significantly greater expression of senescence markers, which included senescence-associated β-galactosidase, p21, and p16, and distinct chromatin changes within Schwann cells.

CONCLUSIONS: This study shows that axon regeneration is reduced in long compared with short isografts, where long isografts contained an environment with an increased accumulation of senescent markers. Although autografts are considered the gold standard for grafting, these results demonstrate that we must continue to strive for improvements in the autograft regenerative environment.

Author List

Hoben GM, Ee X, Schellhardt L, Yan Y, Hunter DA, Moore AM, Snyder-Warwick AK, Stewart S, Mackinnon SE, Wood MD

Author

Gwendolyn M B Hoben MD Assistant Professor in the Plastic Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Autografts
Cellular Senescence
Male
Nerve Regeneration
Random Allocation
Rats, Inbred Lew
Sciatic Nerve
Transplantation, Autologous