Stem cells cause calcification of blood vessels in chronic kidney disease, researchers discover

By John Murphy, MDLinx
Published September 8, 2016

Key Takeaways

Researchers have found a specific type of stem cell, Gli1+, that contributes to the calcification of blood vessels in people with chronic kidney disease (CKD), according to a new study published September 8, 2016 in Cell Stem Cell. The researchers also showed that removing Gli1+ stem cells greatly reduced vascular calcification in CKD—a finding that offers the hope of treatment for these patients.

People with CKD have an extremely high risk for cardiovascular morbidity and mortality, and vascular calcification is a significant contributor to cardiovascular disease. “In the past, this calcification process was viewed as passive—just mineral deposits that stick to the walls of vessels, like minerals sticking to the walls of water pipes,” said senior author Benjamin D. Humphreys, MD, PhD, Director of the Division of Nephrology at Washington University School of Medicine in St. Louis, MO.

“More recently, we’ve learned that calcification is an active process directed by cells,” he explained. “But there has been a lot of controversy over which cells are responsible and where they come from.”

Based on findings from previous studies, Dr. Humphreys and research colleagues at Brigham and Women’s Hospital in Boston, MA, speculated whether Gli1+ cells might play a role in vascular regeneration and disease. Because Gli1+ cells are mesenchymal stem cell-like cells, they have the potential to become different types of connective tissue cells, including smooth muscle, fat, or bone.

For this study, the researchers used genetic analysis in mice to demonstrate that, under normal circumstances, Gli1+ cells do indeed become new smooth muscle cells that help to repair damaged blood vessels. But in the setting of chronic kidney disease, these stem cells likely receive confusing signals and instead become osteoblast-like cells, which deposit calcium in the blood vessel walls.

“We expect to find osteoblasts in bone, not blood vessels,” Dr. Humphreys explained. “In the mice with chronic kidney disease, Gli1+ cells end up resembling osteoblasts, secreting bone in the vessel wall. During kidney failure, blood pressure is high and toxins build up in the blood, promoting inflammation. These cells may be trying to perform their healing role in responding to injury signals, but the toxic, inflammatory environment somehow misguides them into the wrong cell type.”

The researchers next investigated what would happen if they genetically ablated Gli1+ cells in transgenic mice. They found that doing so prevented calcification in the vascular walls of the mice.

“Now that we have identified Gli1+ cells as responsible for depositing calcium in the arteries, we can begin testing ways to block this process,” Dr. Humphreys said. “A drug that works against these cells could be a new therapeutic way to treat vascular calcification, a major killer of patients with kidney disease. But we have to be careful because we believe these cells also play a role in healing injured smooth muscle in blood vessels, which we don’t want to interfere with.”

The researchers called for further studies to investigate novel therapeutic targets in vascular calcification.

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