The injection of stem cells into the carotid artery of brain-injured rats allows the stem cells to move directly to the brain where they greatly enhance brain repair and healing, speeding functional neurological recovery.
This stem cell injection technique was combined with imaging to track the injected stem cells after their introduction into the animal. This study is part of a larger project to study the feasibility of stem cell treatments for traumatic brain injury (TBI) in humans. This research group is being led by Dr. Toshiya Osanai of Hokkaido University Graduate School of Medicine, Sapporo, Japan.
In this experiment, traumatic brain injuries were induced in laboratory rats, and seven days later, bone marrow stem cells were isolated and injected into the carotid arteries. Since injections directly into the brain are dangerous and can cause further brain damage, a technique that places stem cells into the peripheral circulation is preferable. However, many animal and clinical studies have shown that stem cells placed into the peripheral circulation tend to get stuck in the lungs, spleen, liver, and other places. For example, Wang W, et al Cell Transplant 2010;19(12):1599-1607 injected bone marrow mesenchymal stem cells into the heart of rats that had recently experienced a heart attack, and found the many of the injected stem cells stayed in the heart, but many others spread to the lungs, spleen, and lungs. This finding has been confirmed by several other studies as well (Zhang H, et al J Thorac Cardiovasc Surg. 2007;134(5):1234-40 & Wang W, et al, Regen Med. 2011;6(2):179-90). Therefore, Osanai’s research group decided to inject stem cells into the blood vessels that directly feed the brain. This way, the stem cells should find their way to the brain without getting lost in general circulation.
Before injection, the bone marrow stem cells were labeled with “quantum dots,” which are a biocompatible, fluorescent semiconductor created using nanotechnology. The quantum dots emit near-infrared light. Near-infrared light has very long wavelengths that penetrate bone and skin, which allowed the researchers to noninvasively monitor the stem cells for four weeks after transplantation.
Using this in vivo combination of optical imaging and carotid injection, Osanai and colleagues observed the bone marrow-derived stem cells enter the brain on the “first pass,” without entering 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 showed significant recovery of motor function (movement), while untreated rats showed no such 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.
Stem cells from bone marrow are likely to become an important new treatment for patients with traumatic brain injuries and stroke. Bone marrow stem cells, like the ones used in this study, are a promising source of donor cells. However, despite the many questions that remain regarding the optimal timing, dose, and route of stem cell delivery.
In the new animal experiments, stem cell transplantation was performed one week after a traumatic brain injury, which is a “clinically relevant” time, since it takes at least that long to develop stem cells from bone marrow. Injecting such stem cells into the carotid artery is a relatively simple procedure that delivers the cells directly to the brain.
These experiments also add to the evidence that stem cell treatment can promote healing after traumatic brain injury, with significant recovery of function. Osanai and colleagues wrote that, 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.”
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. Clearly further studies are warranted to apply in vivo optical imaging clinically.