Wound Healing in Mammals and Amphibians: Toward Limb Regeneration in Mammals

2012 ◽  
pp. 33-49 ◽  
Author(s):  
Aiko Kawasumi ◽  
Natsume Sagawa ◽  
Shinichi Hayashi ◽  
Hitoshi Yokoyama ◽  
Koji Tamura
Keyword(s):  
Wound Healing ◽  
Limb Regeneration

Role of prostaglandins in amphibian limb regeneration

1981 ◽  
Vol 59 (1) ◽  
pp. 136-137
Author(s):  
Steven R. Scadding
Keyword(s):  
Wound Healing ◽  
Acetylsalicylic Acid ◽  
Limb Regeneration ◽  
Limb Amputation ◽  
Prostaglandin E ◽  
Notophthalmus Viridescens ◽  
Bufo Americanus ◽  
Histological Appearance

Following limb amputation in the newt (Notophthalmus viridescens), the animals were given daily intraperitoneal injections of 0.1 or 1.0 mg of either indomethacin or acetylsalicylic acid. This had no observable influence on the rate or extent of limb regeneration or the histological appearance of the regenerating limb when compared with controls. Following limb amputation in toads (Bufo americanus), the limb stumps were injected daily for the first 15 days after amputation with 5 μg of either prostaglandin E1 or prostaglandin E2. Neither of these treatments had any observed effect on subsequent wound healing of the limbs when compared with controls. These observations suggest that prostaglandins do not play a major role in control of amphibian limb regeneration.

scholarly journals Limb Regeneration in Axolotl: Is It Superhealing?

2006 ◽  
Vol 6 ◽  
pp. 12-25 ◽  
Author(s):  
Stéphane Roy ◽  
Mathieu Lévesque
Keyword(s):  
Spinal Cord ◽  
Functional Analysis ◽  
Wound Healing ◽  
Limb Regeneration ◽  
Therapeutic Approaches ◽  
Adult Tissue ◽  
Regenerative Capacity ◽  
New Developments ◽  
Multiple Structures

The ability of axolotls to regenerate their limbs is almost legendary. In fact, urodeles such as the axolotl are the only vertebrates that can regenerate multiple structures like their limbs, jaws, tail, spinal cord, and skin (the list goes on) throughout their lives. It is therefore surprising to realize, although we have known of their regenerative potential for over 200 years, how little we understand the mechanisms behind this achievement of adult tissue morphogenesis. Many observations can be drawn between regeneration and other disciplines such as development and wound healing. In this review, we present new developments in functional analysis that will help to address the role of specific genes during the process of regeneration. We also present an analysis of the resemblance between wound healing and regeneration, and discuss whether axolotls are superhealers. A better understanding of these animals' regenerative capacity could lead to major benefits by providing regenerative medicine with directions on how to develop therapeutic approaches leading to regeneration in humans.

scholarly journals Integrative Analysis of Axolotl Gene Expression Data From Regenerative and Wound Healing Limb Tissues

2019 ◽  
Author(s):  
Mustafa Sibai ◽  
Cüneyd Parlayan ◽  
Pelin Tuğlu ◽  
Gürkan Öztürk ◽  
Turan Demircan
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Differential Expression Analysis ◽  
Limb Regeneration ◽  
Ambystoma Mexicanum ◽  
Integrative Analysis ◽  
Control Group ◽  
Rna Seq ◽  
Amputation Injury ◽  
Study Designs

ABSTRACTAxolotl (Ambystoma mexicanum) is a urodele amphibian endowed with remarkable regenerative capacities manifested in scarless wound healing and full restoration of amputated limbs. Several regenerative cues of the axolotl limb were successfully unraveled due to the advent of high-throughput technologies and their employment in tackling research questions on several OMICS levels. The field of regenerative biology and medicine has therefore utilized the axolotl as a major and powerful experimental model. Studies which have previously unraveled differentially expressed (DE) genes en masse in different phases of the axolotl limb regeneration have primarily used microarrays and RNA-Seq technologies. However, as different labs are conducting such experiments, sufficient consistency may be lacking due to statistical limitations arising from limited number of sample replicates as well as possible differences in study designs. This study, therefore, aims to bridge such gaps by performing an integrative analysis of publicly available microarray and RNA-Seq data from axolotl limb samples having comparable study designs. Three biological groups were conceived for the analysis; homeostatic tissues (control group), from amputation/injury timepoint up to around 50 hours post amputation (wound healing group), and from 50 hours to 28 days post amputation/injury (regenerative group). Integrative analysis was separately carried out on the selected microarray and RNA-Seq data from axolotl limb samples using the “merging” method. Differential expression analysis was separately implemented on the processed data from both technologies using the R/Bioconductor “limma” package. A total of 1254 genes (adjusted P < 0.01) were found DE in regenerative samples compared to the control, out of which 351 showed magnitudes of Log Fold Changes (LogFC) > 1 and were identified as the top DE genes from data of both technologies. Downstream analyses illustrated consistent correlations of the logFCs of DE genes distributed among the biological comparisons, within and between both technologies. Gene ontology annotations demonstrated concordance with the literature on the biological process involved in the axolotl limb regeneration. qPCR analysis validated the observed gene expression level differences between regenerative and control samples for a set of five genes. Future studies may benefit from the utilized concept and approach for enhanced statistical power and robust discovery of biomarkers of regeneration.

Surface potentials and the control of amphibian limb regeneration

Development ◽  
1979 ◽  
Vol 53 (1) ◽  
pp. 213-223
Author(s):  
B. Lassalle
Keyword(s):  
Wound Healing ◽  
Limb Regeneration ◽  
Wound Surface ◽  
Surface Potentials ◽  
Variable Period ◽  
The Relationship

The relationship between surface potentials and amphibian limb regeneration is examined. The wound surface becomes increasingly positive for several days after amputation but then decreases again, often becoming negative for a variable period during blastemal growth. The same changes of surface potentials are observed during wound healing alone, in the absence of amputation and following amputation of irradiated or denervated limbs. Similar changes occur in non-regenerating frog arms. These observations and other cited reasons lead to the conclusion that surface potentials do not control regeneration.

Limb regeneration in Amphiuma tridactylum (Amphibia, Urodela)

1978 ◽  
Vol 56 (11) ◽  
pp. 2327-2332 ◽  
Author(s):  
Steven R. Scadding
Keyword(s):  
Wound Healing ◽  
Body Wall ◽  
Histological Study ◽  
Limb Regeneration ◽  
Complete Loss ◽  
The Body ◽  
Limb Amputation ◽  
Slow Process

This paper reports a histological study of the response of Amphiuma to simple limb amputation. The results of simple limb amputation in this species are variable. Some limbs undergo wound healing only, others regress, resulting in complete loss of the limb except for a residual rudiment embedded in the body wall, and still others produce heteromorphic limb regenerates of size comparable with the amputated limb. Heteromorphic limb regeneration when it occurs in Amphiuma is a very slow process compared with other urodeles. After 7.5 months (longest observed specimens in this study), the process was still not complete.

scholarly journals Integrative Analysis of Axolotl Gene Expression Data from Regenerative and Wound Healing Limb Tissues

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mustafa Sibai ◽  
Cüneyd Parlayan ◽  
Pelin Tuğlu ◽  
Gürkan Öztürk ◽  
Turan Demircan
Keyword(s):  
Wound Healing ◽  
Statistical Power ◽  
Limb Regeneration ◽  
Ambystoma Mexicanum ◽  
Integrative Analysis ◽  
Pcr Analysis ◽  
P Value ◽  
Rna Seq ◽  
Study Designs ◽  
Merging Method

AbstractAxolotl (Ambystoma mexicanum) is a urodele amphibian endowed with remarkable regenerative capacities manifested in scarless wound healing and restoration of amputated limbs, which makes it a powerful experimental model for regenerative biology and medicine. Previous studies have utilized microarrays and RNA-Seq technologies for detecting differentially expressed (DE) genes in different phases of the axolotl limb regeneration. However, sufficient consistency may be lacking due to statistical limitations arising from intra-laboratory analyses. This study aims to bridge such gaps by performing an integrative analysis of publicly available microarray and RNA-Seq data from axolotl limb samples having comparable study designs using the “merging” method. A total of 351 genes were found DE in regenerative samples compared to the control in data of both technologies, showing an adjusted p-value < 0.01 and log fold change magnitudes >1. Downstream analyses illustrated consistent correlations of the directionality of DE genes within and between data of both technologies, as well as concordance with the literature on regeneration related biological processes. qRT-PCR analysis validated the observed expression level differences of five of the top DE genes. Future studies may benefit from the utilized concept and approach for enhanced statistical power and robust discovery of biomarkers of regeneration.

scholarly journals Timing Does Matter: Nerve-Mediated HDAC1 Paces the Temporal Expression of Morphogenic Genes During Axolotl Limb Regeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Mu-Hui Wang ◽  
Chia-Lang Hsu ◽  
Cheng-Han Wu ◽  
Ling-Ling Chiou ◽  
Yi-Tzang Tsai ◽  
...  
Keyword(s):  
Wound Healing ◽  
Time Course ◽  
Epigenetic Modification ◽  
Limb Regeneration ◽  
Transcriptional Response ◽  
Enrichment Analysis ◽  
Dependent Manner ◽  
Blastema Formation ◽  
Histone Deacetylase 1 ◽  
Regulated Gene Expression

Sophisticated axolotl limb regeneration is a highly orchestrated process that requires highly regulated gene expression and epigenetic modification patterns at precise positions and timings. We previously demonstrated two waves of post-amputation expression of a nerve-mediated repressive epigenetic modulator, histone deacetylase 1 (HDAC1), at the wound healing (3 days post-amputation; 3 dpa) and blastema formation (8 dpa onward) stages in juvenile axolotls. Limb regeneration was profoundly inhibited by local injection of an HDAC inhibitor, MS-275, at the amputation sites. To explore the transcriptional response of post-amputation axolotl limb regeneration in a tissue-specific and time course-dependent manner after MS-275 treatment, we performed transcriptome sequencing of the epidermis and soft tissue (ST) at 0, 3, and 8 dpa with and without MS-275 treatment. Gene Ontology (GO) enrichment analysis of each coregulated gene cluster revealed a complex array of functional pathways in both the epidermis and ST. In particular, HDAC activities were required to inhibit the premature elevation of genes related to tissue development, differentiation, and morphogenesis. Further validation by Q-PCR in independent animals demonstrated that the expression of 5 out of 6 development- and regeneration-relevant genes that should only be elevated at the blastema stage was indeed prematurely upregulated at the wound healing stage when HDAC1 activity was inhibited. WNT pathway-associated genes were also prematurely activated under HDAC1 inhibition. Applying a WNT inhibitor to MS-275-treated amputated limbs partially rescued HDAC1 inhibition, resulting in blastema formation defects. We propose that post-amputation HDAC1 expression is at least partially responsible for pacing the expression timing of morphogenic genes to facilitate proper limb regeneration.

Applying Amphibian Limb Regeneration to Human Wound Healing

2010 ◽  
Vol 65 (5) ◽  
pp. 504-510 ◽  
Author(s):  
Bjoern Menger ◽  
Peter M. Vogt ◽  
Joern W. Kuhbier ◽  
Kerstin Reimers
Keyword(s):  
Wound Healing ◽  
Limb Regeneration
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