Bone marrow stromal cell treatment improves functional outcome, helps repair biostructural damage from traumatic brain injury

The study investigated the effects of treatment with bone MSC on axonal sprouting in the spinal cord after TBI. The axonal regeneration that occurred was correlated with functional recovery. Researchers used adult male Wistar rats (n=8), which were injured with controlled cortical impact and treated with MSCs (3x10 6) impregnated into collagen scaffolds and transplanted into the lesion cavity one week after TBI. Control animals (n=8) were injected intracerebrally with saline. On day 21 after TBI, biotinylated dextran amine (BDA, 10,000 MW) was injected into the collateral motor cortex stereotactically to label the corticospinal tract (CST). Sensorimotor function was tested with neurological severity scores (NSS) and foot fault tests. All rats were sacrificed 35 days after TBI, with the brain and spinal cord sections stained for immuhohistological analysis. The results of this study, Treatment of traumatic brain injury with marrow stromal cells induces axonal sprouting in denervated spinal cord, will be presented by Asim Mahmood, MD, FAANS on Tuesday, April 30. Co-authors are Hongtao Wu, MD; Changsheng Qu, MD; and Ye Xiong, MD.

Those results found very few BDA-labeled CST fibers crossing over the midline in the spinal cord transverse sections of the control rats. However, MSC treatment significantly increased axonal sprouting from the intact CST into the denervated side of the spinal cord at both the cervical and lumbar levels (p, less than 0.05). Functional analysis showed significant improvement with NSS (p, less than 0.05) and foot fault tests (p, less than 0.05) in MSC-treated rats. Pearson's correlation data showed significant correlation between the number of crossing CST fibers and sensorimotor recovery (p, less than 0.05). The researchers concluded that MSC treatment increases axonal sprouting into the denervated side of the spinal cord after TBI, and this is at least partially responsible for the therapeutic benefits of MSC treatment of TBI.

"We have conducted several studies, short- and long-term, which showed very significant sensorimotor recovery," said Asim Mahmood, MD, FAANS, who cited 11 different studies [available upon request from John Iwanski]. "We used multimodality testing to analyze different neurological functions such as learning, memory, (Moris water maze test) and sensorimotor function (NSS and foot fault tests), and recovery was shown consistently. Further studies are not needed to substantiate the functional benefits of this therapy. What is still needed are mechanistic studies to investigate how the MSC treatment promotes functional recovery, and this is what our present research focuses on."

"Our data clearly shows that MSC treatment improves functional outcome and repairs biostructural damage resulting from TBI," added Dr. Mahmood. "This is translation research and clinical trials can be designed to use MSCs to treat TBI. MSC treatment has already been used in cardiovascular medicine."