Regeneration and Regrowth Potentials of Digit Tips in Amphibians and Mammals

Choi, Yun‐Jaie; Meng, Fanwei; Cox, Charles S.; Lally, Kevin P.; Huard, Johnny; Li, Yong

doi:10.1155/2017/5312951

Cited by 11 publications

(16 citation statements)

References 140 publications

(178 reference statements)

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“…Limb amputation in mammals triggers a series of events that ultimately result in healing and fibrotic scar formation (reviewed in 12 ); with some exceptions such as mouse digit tip amputation and, human fingertip which under special conditions have been shown to regenerate.…”

Section: Discussionmentioning

confidence: 99%

“…In healing/scarring injury response, following hemostasis and the inflammation phases, proliferation takes over in which case collagen deposition, new vascularization and an increase in fibroblast activity occur (reviewed in 12 ). The deposition of collagen and fibronectin form a provisional extracellular matrix (ECM), and proliferating epithelial cells cover the wounded tissues (reviewed in 13 ).…”

Section: Introductionmentioning

confidence: 99%

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

Oliveira

Barker

Berezikov

et al. 2019

Sci Rep

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Oliveira

Barker

Berezikov

et al. 2019

Sci Rep

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“…In all vertebrates, THs are not only critical for regulating growth and development, but also for regulating energy metabolism ( Frieden, 1981 ; Sheridan, 1994 ; Choi et al, 2017 ). If the TH concentration changes due to endocrine disruption by environmental stressors, a whole suite of physiological processes may be influenced ( Hulbert and Else, 2004 ; Steyermark et al, 2005 ; Ruthsatz et al, 2018b , 2018c , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Shifts in sensitivity of amphibian metamorphosis to endocrine disruption: the common frog (Rana temporaria) as a case study

Ruthsatz

Dausmann

Paesler

et al. 2020

Conservation Physiology

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Effective conservation actions require knowledge on the sensitivity of species to pollution and other anthropogenic stressors. Many of these stressors are endocrine disruptors (EDs) that can impair the hypothalamus–pituitary–thyroid axis and thus alter thyroid hormone (TH) levels with physiological consequences to wildlife. Due to their specific habitat requirements, amphibians are often sentinels of environmental degradation. We investigated how altered TH levels affected the bioenergetics of growth and development (i.e. age, size, metabolism, cardiac function and energy stores) before, during and after metamorphosis in the European common frog (Rana temporaria). We also determined how ontogenetic stage affected susceptibility to endocrine disruption and estimated juvenile performance. TH levels significantly affected growth and energetics at all developmental stages. Tadpoles and froglets exposed to high TH levels were significantly younger, smaller and lighter at all stages compared to those in control and low TH groups, indicating increased developmental and reduced growth rates. Across all ontogenetic stages tested, physiological consequences were rapidly observed after exposure to EDs. High TH increased heart rate by an average of 86% and reduced energy stores (fat content) by 33% compared to controls. Effects of exposure were smallest after the completion of metamorphosis. Our results demonstrate that both morphological and physiological traits of the European common frog are strongly impacted by endocrine disruption and that ontogenetic stage modulates the sensitivity of this species to endocrine disruption. Since endocrine disruption during metamorphosis can impair the physiological stress response in later life stages, long-term studies examining carry-over effects will be an important contribution to the conservation physiology of amphibians.

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“…In the short term, we can use well studied mammalian wound healing as a guide for the use of these modalities in wound healing. In a non-regenerative mammalian context, an epithelial wound or digit tip wound are followed by re-epithelialization, inflammation, proliferation, and fibrotic scarring (Gurtner et al, 2008; Choi et al, 2017). A spinal cord injury slightly differs as it does not undergo re-epithelialization and the scar is a product of reactive gliosis (Ahuja et al, 2017).…”

Section: Relationships Between Wounding Responses and Looking Ahead mentioning

confidence: 99%

More Than Just a Bandage: Closing the Gap Between Injury and Appendage Regeneration

Kakebeen

Wills

2019

Front. Physiol.

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The remarkable regenerative capabilities of amphibians have captured the attention of biologists for centuries. The frogs Xenopus laevis and Xenopus tropicalis undergo temporally restricted regenerative healing of appendage amputations and spinal cord truncations, injuries that are both devastating and relatively common in human patients. Rapidly expanding technological innovations have led to a resurgence of interest in defining the factors that enable regenerative healing, and in coupling these factors to human therapeutic interventions. It is well-established that early embryonic signaling pathways are critical for growth and patterning of new tissue during regeneration. A growing body of research now indicates that early physiological injury responses are also required to initiate a regenerative program, and that these differ in regenerative and non-regenerative contexts. Here we review recent insights into the biophysical, biochemical, and epigenetic processes that underlie regenerative healing in amphibians, focusing particularly on tail and limb regeneration in Xenopus. We also discuss the more elusive potential mechanisms that link wounding to tissue growth and patterning.

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Regeneration and Regrowth Potentials of Digit Tips in Amphibians and Mammals

Cited by 11 publications

References 140 publications

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

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

Shifts in sensitivity of amphibian metamorphosis to endocrine disruption: the common frog (Rana temporaria) as a case study

More Than Just a Bandage: Closing the Gap Between Injury and Appendage Regeneration

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