Intra-arterial technique of stem cell transplantation may enhance functional recovery from TBI

Feb 2 2012

Experiments in brain-injured rats show that stem cells injected via the carotid artery travel directly to the brain, where they greatly enhance functional recovery, reports a study in the February issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

The carotid artery injection technique—along with some form of in vivo optical imaging to track the stem cells after transplantation—may be part of emerging approaches to stem cell transplantation for traumatic brain injury (TBI) in humans, according to the new research, led by Dr Toshiya Osanai of Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Advanced Imaging Technology Lets Researchers Track Stem Cells
The researchers evaluated a new "intra-arterial" technique of stem cell transplantation in rats. Within seven days after induced TBI, stem cells created from the rats' bone marrow were injected into the carotid artery. The goal was to deliver the stem cells directly to the brain, without having them travel through the general circulation.

Before injection, the stem cells were labeled with "quantum dots"—a biocompatible, fluorescent semiconductor created using nanotechnology. The quantum dots emit near-infrared light, with much longer wavelengths that penetrate bone and skin. This allowed the researchers to noninvasively monitor the stem cells for four weeks after transplantation.

Using this in vivo optical imaging technique, Dr Osanai and colleagues were able to see that the injected stem cells entered the brain on the "first pass," without entering the general circulation. Within three hours, the stem cells began to migrate from the smallest brain blood vessels (capillaries) into the area of brain injury.

After four weeks, rats treated with stem cells had significant recovery of motor function (movement), while untreated rats had no recovery. Examination of the treated brains confirmed that the stem cells had transformed into different types of brain cells and participated in healing of the injured brain area.

Further Progress toward Stem Cell Therapy for Brain Injury in Humans
Stem cells are likely to become an important new treatment for patients with brain injuries, including TBI and stroke. Bone marrow stem cells, like the ones used in the new study, are a promising source of donor cells. However, many questions remain about the optimal timing, dose, and route of stem cell delivery.

In the new animal experiments, stem cell transplantation was performed one week after TBI—a "clinically relevant" time, as it takes at least that long to develop stem cells from bone marrow. Injecting stem cells into the carotid artery is a relatively simple procedure that delivers the cells directly to the brain.

The experiments also add to the evidence that stem cell treatment can promote healing after TBI, with significant recovery of function. With the use of in vivo optical imaging, "The present study was the first to successfully track donor cells that were intra-arterially transplanted into the brain of living animals over four weeks," Dr Osanai and colleagues write.

Some similar form of imaging technology might be useful in monitoring the effects of stem cell transplantation in humans. However, tracking stem cells in human patients will pose challenges, as the skull and scalp are much thicker in humans than in rats. "Further studies are warranted to apply in vivo optical imaging clinically," the researchers add.