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How the immune system responds to damage to many organs and tissues, enabling them to repair and regenerate
.
A new study from the Stowers Institute for Medical Research used highly regenerated zebrafish to investigate the timing and genetic procedures
of macrophages (a type of white blood cell) during the repair and regeneration of zebrafish sensory organs.
Recently, postdoctoral researcher Dr.
Piotrowski said: "Organ regeneration provides an exciting opportunity to study the immune system and explore why some species can regenerate organs such as hearts or missing limbs, while species like humans cannot
.
Zebrafish sensory organ hair cells are an ideal system for studying regeneration pathways and cell types because they are easily destroyed by antibiotics and begin regeneration
within 5 hours.
"Our hypothesis is that human macrophages have not received the proper chemical activation 'cocktail' to guide the pro-regenerative process," Denans said
.
Macrophages (literally translated as "big eaters" in Latin) are essential for organ regeneration, engulfing foreign particles such as dead cells and bacteria and digesting them
with enzymes.
During zebrafish sensory hair cell death and regeneration, it is critical to study macrophages at high spatial resolution and at multiple tightly spaced
time points.
"New evidence is a valuable resource for comparative studies of genetic procedures for macrophage-mediated repair and regeneration," Deans said
.
While this study marks the first time that successive macrophage states have been broken down with unusual precision, preliminary comparisons with previously reported pathways of different organs and species suggest that this mechanism may be conserved
.
"When you look closely, macrophages not only need to initiate regeneration, but they also interact with the brain by communicating with nerve cells to rebuild and maintain synapses
necessary for the normal functioning of the regenerated organs," Piotrowski said.
The team hopes that additional research based on this new discovery may provide a basis for designing tailored immunotherapies to reduce disease and potentially make animals with limited regenerative capacity, such as humans, more regenerative
.
"This is just one of a series of steps to consider developing ideas for regenerative immunotherapy in humans," Denans said
.
Other authors include Nhung T.
The work was funded by the National Institutes of Health for Deafness and Other Communication Disorders (award 1R01DC015488-01A1) and institutional support
from the Stols Institute for Medicine.
Journal Reference:
Nicolas Denans, Nhung T.