Spiny Mice Can Regenerate Kidney Tissue Without Scarring

Spiny mice are one of the very few mammalian species in which adults can repeatedly regenerate at least some tissues without scarring and loss of tissue function. This has been observed in their ability to slough off skin as a way to confound predators, then regrow that skin. They can also regrow nerves and cartilage. Researchers pursuing an understanding of the molecular biology of proficient regeneration have found that the behavior of macrophages and senescent cells is meaningfully different in species capable of regeneration, such as the spiny mice, salamanders, and zebrafish. Salamanders, for example, possess macrophages that are far better at clearing senescent cells than is the case in our species. The hope is that the relevant mechanisms to allow scarless regeneration from injury remain present in most mammals, but are repressed or dormant, silenced in a way that will be comparatively easy to undo.

Regeneration following injury, and tissue maintenance in general, is a complex dance between stem cells, somatic cells, senescent cells, and supporting immune cells such as macrophages. Senescent cells form to help provoke tissue growth and contribute to the inflammatory signaling that draws in immune cells to play their parts. Those immune cells destroy senescent cells after their task is complete. Something in the interplay between macrophages and senescent cells appears critical to scarless regeneration, based on the evidence to date. This may be a complex set of differences in signaling, or it may turn out to hinge on just a few regulatory genes. Whether there is a basis for therapy here that can be exploited in the near future to allow humans to fully regenerate from severe injuries remains an open question.

Spiny mice regenerate damaged kidneys without scarring

Earlier studies of wound healing in spiny mice suggested that the animals had - over the course of their evolution - solved the problem of tissue fibrosis (scarring) after injury. But could they also heal damaged internal organs the same way? To find out, they exposed spiny mice to conditions that are known to cause serious kidney injury. Their studies showed that, although spiny mice suffered the same degree of tissue injury initially, they were nevertheless able to completely heal: they regenerated an apparently healthy kidney with no signs of fibrosis. As expected, other mice treated in the same way progressed to organ failure.

"The dramatic and complete recovery of kidney function over a two-week time course in spiny mice was quite surprising to us. The types of severe injuries we used were chosen because they produce a decisive and rapid loss of kidney function in mice and led to complete organ failure over the same two-week period." To find out how the spiny mice do it, the researchers took a comprehensive look at the genes they express. Their studies suggest that the spiny mouse genome is poised at the time of injury to launch a rapid, scarless regenerative response in surviving kidney cells. The analysis uncovered differences in the activity of 843 genes in six unique clusters. Researchers also saw a delayed response by immune cells called macrophages, which are known to play a role in fibrosis. Unlike in other mice, macrophages didn't appear on the scene for about a week.

Spiny mice activate unique transcriptional programs after severe kidney injury regenerating organ function without fibrosis

Fibrosis-driven solid organ failure is an enormous burden on global health. Spiny mice are terrestrial mammals that can regenerate severe skin wounds without scars to avoid predation. Whether spiny mice also regenerate internal organ injuries is unknown. Here, we show that despite equivalent acute obstructive or ischemic kidney injury, spiny mice fully regenerate nephron structure and organ function without fibrosis, whereas C57Bl/6 or CD1 mice progress to complete organ failure with extensive renal fibrosis. Two mechanisms for vertebrate regeneration have been proposed that emphasize either extrinsic (pro-regenerative macrophages) or intrinsic (surviving cells of the organ itself) controls. Comparative transcriptome analysis revealed that the spiny mouse genome appears poised at the time of injury to initiate regeneration by surviving kidney cells, whereas macrophage accumulation was not detected until about day 7. Thus, we provide evidence for rapid activation of a gene expression signature for regenerative wound healing in the spiny mouse kidney.


It is interesting that the spiny mouse is prone to developing diabetes. As per wikipedia:
Captive housing of spiny mice in the mid-1960s uncovered their sensitivity to developing diabetes.

Posted by: Cuberat at November 10th, 2021 3:24 PM

And some after hours question.

Did anyone research how do the spiny mice regenerate peripheral and central nerve damage?

Posted by: Cuberat at November 12th, 2021 7:13 AM
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