By discovering how adult neural stem cells navigate to injury sites in the CNS, UC Irvine researchers have helped solve a puzzle in the creation of stem cell-based treatments: how do these cells know where to go?
Tom Lane and Kevin Carbajal of the Sue & Bill Gross Stem Cell Research Center found the answer with the body’s immune system.
Their study not only identifies an important targeting mechanism in transplanted stem cells but also provides a blueprint for engineering stem cell-based therapies for multiple sclerosis (MS) and other chronic neurologic diseases in which inflammation occurs. Results appear in this week’s early online edition of the Proceedings of the National Academy of Sciences.
“Previously, we’ve seen that adult neural stem cells injected into the spinal column knew, amazingly, exactly where to go,” said Lane, Chancellor’s Fellow and professor of molecular biology and biochemistry. “We wanted to find what directed them to the right injury spots.”
The researchers used adult neural stem cells to treat mice with a disease similar to multiple sclerosis that destroys myelin, causing chronic pain and loss of motor function. Adult neural stem cells have shown the ability to differentiate into oligodendrocytes, the building blocks of myelin, and repair or replace affected tissue.
In the mice, inflammatory cells — reacting to the virally induced nerve damage — were observed activating receptors on the adult neural stem cells. These CXCR-4 receptors, in turn, recruited chemokine proteins called CXCL-12 that guided the stem cells to specific sites. Chemokines are produced in acute and chronic inflammation to help mobilize white blood cells.
As the stem cells migrated through the CNS, they began to transform into the precursor cells for oligodendrocytes. Latching onto their repair sites, they continued the differentiation process. Three weeks after the initial treatment, 90% of the cells had grown into fully formed oligodendrocytes.
In earlier work, Lane and colleagues demonstrated that adult neural stem cell treatments improved motor function in mice with chronic multiple sclerosis symptoms.
“In this study, we’ve taken an important step by showing the navigational cues in an inflammatory environment like MS that guide stem cells,” said Lane. “Hopefully, these cues can be incorporated into stem cell-based treatments to enhance their ability to repair injury.”
The study received support from the National Institutes of Health and the National Multiple Sclerosis Society.
Source: News Release
University of California - Irvine
June 1 , 2010