• Biotherapeutics

    Stem Cell Signaling May Repair Liver Injury

Tushar Patel, M.B., Ch.B.

Researchers are continually learning more about the ability of stem cells to replace or repair damaged tissue. As it turns out, a signaling mechanism used by stem cells may also have therapeutic effects.

Two new studies from the lab of Tushar Patel, M.B., Ch.B., have suggested the salubrious effect stem cell extracellular vesicles, or EVs, may have on injured liver tissue. EVs are tiny pouches of molecules—including proteins, RNA and even some DNA—that are released by cells as a form of communication with other cells in the body. “They’re like Tweets, a brief, limited message that gets sent out by a cell and that can influence surrounding cells,” says Dr. Patel. But when the EVs come from bone marrow-derived stem cells, the message appears to promote healing of damaged tissue.

In their findings in Stem Cell Translational Medicine, Dr. Patel’s team explored the effect of EVs on mouse models of acute liver failure. The condition, which is serious in humans, is fatal for mice within hours. When researchers gave a group of mice either an infusion or direct abdominal injection of EVs, they found the vesicles migrated to the injured liver. But the most astounding result was that a day later, more than a half of the group had survived. “The results were quite dramatic,” says Dr. Patel, “and they were beneficial whether the mice received EVs derived from mouse stem cells or from human stem cells.”

As a potential therapy, EVs pose an intriguing alternative to stem cells because they avoid risks, such as the possibility of developing into a tumor. What’s more, the team found the vesicles worked just as well after being frozen for three months. “As we think about developing therapies for unmet patient needs, this means you could collect stem cell EVs, store them, and use them at a later date,” he says.

His group also explored whether stem cell EVs can improve the potentially dangerous inflammation that sometimes occurs in liver tissue following surgery. When reconnected to blood vessels that have been clamped during liver surgery, liver tissue can die from what’s known as ischemia-reperfusion injury. Similarly, reperfusion can present a challenge in liver transplants, especially when the organ is donated after a cardiac death. In the journal Liver Transplantation, Dr. Patel’s team reported that stem cell EVs can mitigate this kind of injury.

In both lab studies and in mouse models of hepatic ischemia, researchers found the reperfused livers fared better when treated with a bath of EVs. Measurements of ALT enzyme levels, an indicator of liver injury, were reduced from 10,000 IU/L to 500 (normal is 40), and the amount of dead tissue in the liver decreased from 50 percent to less than 5 percent. What this means, says Dr. Patel, is that EVs present a promising tool that could be administered to liver tissue after surgery, or before a liver transplant. “Ultimately, EVs might make more livers available nationally, especially at centers that currently pass on donated livers when they come available following a cardiac death,” he says.

- Kate Ledger, April 21