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

Frontiers in Physiology, 2019 · DOI: 10.3389/fphys.2019.00081 · Published: February 8, 2019

Physiology Genetics Regenerative Medicine & Stem Cells

Simple Explanation

Amphibians like Xenopus frogs can regenerate lost limbs and tails as tadpoles, but this ability decreases as they grow into adults. Scientists are studying how these frogs regenerate to understand how to promote regenerative healing in humans. Early injury responses, such as changes in reactive oxygen species (ROS) signaling and membrane potential, are crucial for initiating the regenerative process. These responses differ in regenerative and non-regenerative contexts. Epigenetic modifications, which affect gene expression, also play a key role in regeneration. Understanding these modifications could help activate the gene regulatory program needed for regenerative healing.

Study Duration

Not specified

Participants

Xenopus laevis and Xenopus tropicalis tadpoles

Evidence Level

Review

Key Findings

1
Reactive oxygen species (ROS) signaling is rapidly activated after injury and is required for tail regeneration. Inhibition of ROS prevents full tail regeneration and affects the activation of Wnt signaling pathways.
2
Bioelectrical changes, such as membrane depolarization, are also rapidly triggered by amputation. Depolarization is essential for regeneration, and preventing it leads to regeneration failure.
3
Innate immune cells, like macrophages, are recruited to the injury site and contribute to regenerative healing. Macrophages may release pro-repair interleukins that promote stem cell proliferation.

Research Summary

This review discusses the biophysical, biochemical, and epigenetic processes involved in regenerative healing in amphibians, particularly tail and limb regeneration in Xenopus. The review highlights the importance of early physiological injury responses, such as ROS signaling and membrane potential changes, in initiating a regenerative program. The review also explores the epigenetic landscape and the role of innate immune cells in regulating gene expression and promoting tissue growth and patterning during regeneration.

Practical Implications

Therapeutic Interventions

Understanding the factors that enable regenerative healing in amphibians could lead to new therapeutic interventions for promoting tissue regeneration in humans.

Drug Development

Identifying the key signaling pathways and epigenetic modifications involved in regeneration could facilitate the development of drugs that stimulate regenerative processes.

Clinical Applications

Modulating the immune response and bioelectrical signals at the injury site could improve regenerative outcomes in patients with tissue damage.

Study Limitations

1
The review primarily focuses on tail and limb regeneration in Xenopus, and the findings may not be directly applicable to other species or tissues.
2
The exact mechanisms linking wounding to tissue growth and patterning remain elusive.
3
The role of specific immune cell subpopulations and their molecular characteristics in regenerative versus non-regenerative healing in Xenopus is not yet fully understood.

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