Conference Coverage

Trial: Stem cells may reduce AAA inflammation



CHICAGO – Early results of a trial evaluating allogeneic mesenchymal stem cells to target aortic inflammation in patients with small abdominal aortic aneurysms (AAAs) has reported encouraging early results, according to research presented here at the annual meeting of the Midwestern Vascular Surgery Society.

Katherin Leckie, MD, an integrated vascular surgery resident in the vascular surgery division, Indiana University, Indianapolis, reported on early results from the ARREST (Aneurysm Repression With Mesenchymal Stem Cells) trial. Twenty-one patients have been enrolled so far, and early results showed that treatment with mesenchymal stem cells (MSCs) increased levels of a key anti-inflammatory cell type, the Tr1, in proportion to a key proinflammatory cell type, the Th17.

“In AAA, the Tr1:Th17 ratio is decreased,” Dr. Leckie said. AAA serum stimulates MSC secretion of IL-10. Previously, mouse studies have shown MSCs restore the Tr1:Th17 balance and prevent aneurysms, Dr. Leckie noted.

The ARREST trial is evaluating that finding in humans with small AAAs of 35-50 mm in diameter. When the trial is fully enrolled, the 36 patients are to be evenly divided between three treatment groups: placebo; 1 million MSC/kg; and 3 million MSC/kg. The primary endpoint is change in Tr1:Th17 ratio at 14 days. Secondary endpoints are change in AAA inflammation at 2 weeks and change in AAA diameter and volume at 1-5 years.

At 14 days, the high-dose group had already seen a more than 100% change in Tr1:Th17 ratio (P = .03), versus about a 35% change for the low-dose and no change for the placebo groups. At 28 days, the high-dose group’s change increased to greater than 150%, while that of the low-dose group reached around 50%, with no change in the placebo group.

The study also found a possible trend toward changes in AAA diameter among the three groups after 1 year, Dr. Leckie said. In the placebo group, AAA diameter increased 3.5 mm on average. In the low-dose group, AAA diameter increased almost 1.5 mm. However, in the high-dose group, aortic diameter actually decreased about 0.5 mm (P = .189), Dr. Leckie said.

“MSCs have significantly improved the Tr1:Th17 imbalance at 14 days,” Dr. Leckie said. “There’s also a possible trend toward decreased aortic inflammation at 14 days as well as decreased growth of AAA at 12 months.”

Dr. Leckie had no relevant financial relationships to disclose.

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