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Signaling molecule may help stem cells focus on making bone despite age, disease
Date:3/8/2013

autophagy slows with age, so deadly trash starts piling up in and around cells, Hill said.

"Your cells normally have a reminder to take out the trash," said Dr. Carlos Isales, MCG endocrinologist and Clinical Director of the GRU Institute of Regenerative and Reparative Medicine. "That reminder, SDF-1, becomes inconsistent as you get older, so rather than being an activator of the trash signal, it becomes an inhibitor."

Herberg led efforts to genetically modify stem cells from mice to overexpress SDF-1 in fact the researchers were in the enviable position of being able to adjust expression up or down and control autophagy in their novel cells. They found that while SDF-1 didn't increase stem cell numbers, it protected stem cells hazards related to low oxygen and more by increasing autophagy while decreasing its antithesis, programmed cell death, or apoptosis.

"They get away with lower oxygen needs and lower nutrient needs and stem cells are able to survive in a hostile environment as they are attacked by damaging molecules like free radicals," Hill said. In fact, the cells can thrive.

"The success of stem cell transplants is mixed and we think part of the problem is the environment the cells are put into," said Isales. "Ultimately we want to find out what is the triggering event for aging, what is the chicken, what is the egg and what initiates this cascade. This new finding gives us a piece of the puzzle that helps us see the big picture."

They've already begun looking at what happens to SDF-1 in human bone marrow stem cells and have identified a couple of drugs used to treat other conditions that increase SDF-1 production and protection. They envision a collagen matrix, almost like a raft, that delivers SDF-1 and stem cells or SDF-1 alone where needed, enabling targeted bone regrowth in the case of a bad fracture, for example.

It was already known that stem cells secrete SDF-1 and that the cell survival
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Contact: Toni Baker
tbaker@gru.edu
706-721-4421
Medical College of Georgia at Georgia Regents University
Source:Eurekalert  

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