Searching for the ‘Sweet Spot’ of Tissue Repair

When the body heals improperly, scar tissue develops. But new tools to help immune cells communicate could extend patients' lifespans.

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Your immune system protects you from infection, but it also helps your body with all kinds of repairs. It performs a wide range of tasks, from helping wounds heal to clearing dead cells after organ damage.

“Scar tissue is what happens when things don’t repair well,” says Kelly McNagny, professor of biomedical engineering at the University of British Columbia.

“Normal tissue function is what happens when you do repair damaged tissue. We think immune cells actually play a big role in that, too.”

In the ideal case, immune cells can do their job perfectly. But if their response is too weak or too strong, problems can emerge.

“It looks like very early in life you get exposed to microbiome and other environmental factors, and that tends to educate your immune system,” adds McNagny.

“If your immune system doesn’t get educated well, it tends to rebel and act a little badly and you don’t get great tissue repair. And so we’re trying to figure out in which scenarios that happens.”

Using biomedical engineering tools, it’s now possible to dissect how single cells communicate with each other. That level of detail can illuminate pathways for better repairs by regulating those signals. In some cases that might mean manipulating one cell to stimulate another for to boost the repair response. In others that might mean dampening an over-repair response to prevent damage.

“Our big idea is there is a newly discovered group of immune cells, they’re called innate lymphoid cells — and to me it’s amazing that we can find a new cell type within the past 10 years that nobody even knew about — and those cells live in your tissues throughout your life and they help you repair,” says McNagny.

“If they go awry, if you make too many of them, they can stimulate over-repair and cause you to make scar tissue, get an organ to fail. You see that type of scar tissue forming in things like multiple sclerosis, in Crohn’s disease, in liver failure.”

If researchers can figure out how to ensure that we hit that sweet spot where healthy tissue can be regenerated without scarring, that’s an advance that would help everybody live longer.

“You know if three things are going to kill you, they’re infections, cancer, and fibrotic disease,” says McNagny.

“It’s that fibrotic disease that we really don’t know how to treat. That’s what we’re trying to work on.”

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Kelly McNagny’s research areas include signaling networks, innate immune response, kidney function and cell based therapy. Specifically, McNagny’s laboratory is interested in two aspects of hematopoietic stem cell biology: the networks that regulate the commitment of multipotent progenitors to a specific lineage, and the surface receptors expressed by hematopoietic precursor cells that regulate their interactions with their microenvironment and by mature cells that regulate their trafficking in disease.

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