TY  - JOUR
A1  - Costa Oliveira, Karla Mychellyne
A1  - Barker, John Howard
A1  - Berezikov, Eugene
A1  - Pindur, Lukas
A1  - Kynigopoulos, S.
A1  - Eischen-Loges, Maria José
A1  - Han, Zhihua
A1  - Bhavsar, Mit Balvantray
A1  - Henrich, Dirk
A1  - Leppik, Liudmila
T1  - Electrical stimulation shifts healing/scarring towards regeneration in a rat limb amputation model
T2  - Scientific reports
N2  - 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 from healing/scarring towards regeneration. A better understanding of if and how EStim controls these changes, could lead to strategies that replace scarring with regeneration.
KW  - Developmental biology
KW  - Morphogenesis
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50812
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-508126
SN  - 2045-2322
N1  - Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
VL  - 9
IS  - 1, Art. 11433
SP  - 1
EP  - 14
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -