Electrical stimulation shifts healing/scarring towards regeneration in a rat limb amputation model

Scientific Reports
K M C OliveiraL Leppik

Abstract

Different species respond differently to severe injury, such as limb loss. In species that regenerate, limb loss is met with complete restoration of the limbs' form and function, whereas in mammals the amputated limb's stump heals and scars. In in vitro studies, electrical stimulation (EStim) has been shown to promote cell migration, and osteo- and chondrogenesis. In in vivo studies, after limb amputation, EStim causes significant new bone, cartilage and vessel growth. Here, in a rat model, the stumps of amputated rat limbs were exposed to EStim, and we measured extracellular matrix (ECM) deposition, macrophage distribution, cell proliferation and gene expression changes at early (3 and 7 days) and later stages (28 days). We found that EStim caused differences in ECM deposition, with less condensed collagen fibrils, and modified macrophage response by changing M1 to M2 macrophage ratio. The number of proliferating cells was increased in EStim treated stumps 7 days after amputation, and transcriptome data strongly supported our histological findings, with activated gene pathways known to play key roles in embryonic development and regeneration. In conclusion, our findings support the hypothesis that EStim shifts injury response ...Continue Reading

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Citations

Feb 23, 2020·European Journal of Trauma and Emergency Surgery : Official Publication of the European Trauma Society·Liudmila LeppikJohn Howard Barker
Jul 16, 2020·Hand : Official Journal of the American Association for Hand Surgery·Grace C KeaneMatthew D Wood
Jan 25, 2020·Cellular and Molecular Life Sciences : CMLS·Siwei ZhaoMin Zhao
Jan 6, 2021·BMC Biomedical Engineering·Christina N M RyanDimitrios I Zeugolis
May 21, 2021·Advanced Materials·Giorgio ContaJun Chen
Jul 16, 2021·Biosensors & Bioelectronics·Tom J ZajdelDaniel J Cohen

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Methods Mentioned

BETA
amputation
fluorescence microscopy
light microscopy
RNA-seq
Illumina sequencing

Software Mentioned

GOrilla
REVIGO
STAR
BiAS
FibrilTool
Elements
ImageJ
FunReach
EStim
Ensembl

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