Tracking stem cells by MRI

By Heather Buschman, Ph.D.
April 28, 2011

Neonatal stroke or related brain injuries can occur when a newborn baby’s blood supply is restricted, often leading to cerebral palsy, epilepsy or mental retardation. Over the past decade, researchers have been using animal models to experiment with neural stem cells to replace or protect the damaged tissue in this type of surprisingly common brain injury.

Stem cells hold great therapeutic promise because they can proliferate in a dish (making many cells for transplantation purposes) and then differentiate on command, specializing into a specific cell type like neurons in the brain or even glial cells, which support and protect neurons. Stem cells are also pathotropic, meaning that they are drawn to, or home in on, pathological locations in the brain, including those that can occur from injury (like stroke) or degeneration (such as occurs in Alzheimer’s disease).

But there are risks to stem cell therapy. One worry is that cells will continue proliferating after transplantation, leading to tumor formation. Scientists also need to make sure the stem cells migrate directly to the locations in need of repair or protection and not to unintended locations. These are tough problems to overcome, though, because it’s difficult to track a stem cell’s behavior once it’s inside a host.

“The ability to monitor neural stem cells for a long time is particularly important for newborns, where implantation could cause unanticipated effects in the developing brain long into the future,” says Dr. Evan Y. Snyder, director of Sanford-Burnham’s Stem Cells and Regenerative Biology Program. Dr. Snyder was also the first to demonstrate pathotropism of solid-organ stem cells, as well as the first to demonstrate the use of stem cells to treat stroke, particularly neonatal stroke.

In a paper published recently in the Annals of Neurology, Dr. Snyder and collaborators at Loma Linda University, provide a solution to this problem. They showed that magnetic resonance imaging (MRI) – the same technique already used to diagnose cancer, stroke and many other conditions – can be used to monitor neural stem cell activity in brain-injured mice over long periods.

In this study, the researchers first loaded neural stem cells with iron particles, then transplanted them to mouse pups with hypoxic ischemic injury (similar to that seen in neonatal stroke). Using MRI technology, Dr. Snyder and his colleagues observed the iron-labeled cells in mice for more than a year – the human equivalent of 30 or 40 years. This allowed them to quantify key aspects of neural stem cell behavior, such as location, lifespan, speed of migration, proliferation and integration into host tissues – all in the background of brain injury.

Even better, no adverse consequences were observed. In an editorial that accompanied the paper, Dr. Thyagarajan Subramanian, a neurologist at Pennsylvania State University, highlights the therapeutic potential for these mice:

“…this work confirms findings in previous reports that neural stem cell transplants suppress the host immune response in the neonate, thus rendering stem cell transplants particularly attractive in neonatal brain injury, which has devastating consequences of long-term disability and morbidity in the current clinical setting.”

As always, more questions need to be answered before this type of therapy can be tried in humans. But, as Dr. Subramanian points out, “For the clinical neurologist, patients with neonatal hypoxic injuries, and their caregivers, this study seems to provide a small light at the end of a long tunnel.”

Original papers:

Obenaus, A., Dilmac, N., Tone, B., Tian, H., Hartman, R., Digicaylioglu, M., Snyder, E., & Ashwal, S. (2011). Long-term magnetic resonance imaging of stem cells in neonatal ischemic injury Annals of Neurology, 69 (2), 282-291 DOI: 10.1002/ana.22168

Subramanian, T. (2011). A Small Light at the end of a long tunnel: Long-term magnetic resonance imaging of stem cells in neonatal ischemic injury Annals of Neurology, 69 (2), 232-233 DOI: 10.1002/ana.22379

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Heather Buschman, Ph.D.

Heather was an SBP Communications staff member.


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