Thursday, May 31st 2012

Therapeutic Effects of Intra-Arterial Delivery of Bone Marrow Stromal Cells in Traumatic Brain Injury of Rats

Background
No where in medicine are the dreams for stem cells bigger than in treatment of diseases of the central nervous system. From neurodegenerative diseases to strokes to traumatic brain and spine injuries considerable work has been done. Specific attention being paid to autologous adult bone marrow stem cells which do not carry the risk of cancer, rejection and are readily available. Previous work has documented their ability to cross the blood brain barrier and to differentiate from BMSCs into microglia and neural cells. In a recent edition of Neurosurgery a group from the Hokkaido University Graduate School of Medicine presented BMSC use in a rat model of TBI.

Osanai, Toshiya, Satoshi Kuroda, Taku Sugiyama, Masahito Kawabori, Masaki Ito, Hideo Shichinohe, Yuji Kuge, Kiyohiro Houkin, Nagara Tamaki, and Yoshinobu Iwasaki. “Therapeutic Effects of Intra-Arterial Delivery of Bone Marrow Stromal Cells in Traumatic Brain Injury of Rats – In Vivo Cell Tracking Study by Near-Infrared Fluorescence Imaging.” Neurosurgery 70:435-444, 2012.

A link to the article is here.

Design
The group induced “traumatic” lesions in 12 Sprague-Dawley rats by exposing a unilateral sensorimotor area with craniotomy and applying a freezing 7mm cylinder (cooled in liquid nitrogen) to the dura over the area causing an underlying lesion and significant post injury motor dysfunction.

Of the 12 rats 6 were then injected with an extimated 2 x 10^6 bone marrow stem cells in 200 microliters of saline through the ipsilateral internal carotid and 6 were injected similiarly with 200 microliters of saline. The injections occured 7 days post injury. The group derived the BMSC non-autologous bone marrow from the femurs of other Sprague-Dawley rats after death. These were labeled with PKH26 prior to implantation and with fluroscent cell markers for optical imaging.

The outcomes were functional recovery, in vivo optical imaging and histological examination after euthanasia.

Results
Optical imaging showed that in the ipsilateral side to the injury the injected BMSC left the vasculature and began engrafting into the damaged cortex as quickly as 1-3 hours after injection.

After death of the animals histological examination of the brain showed that the PKH26 labeled cells were primarily to be found in the damaged hemisphere and 22% showed NeuN and 18% showed GFAP implying that the BMSC were differentiating into neural elements.

The implanted animals showed statistically better motor improvement at 2 and 3 weeks post implantation.

Discussion
More importantly than showing functional recovery this paper’s biggest showing is a clinically, real world applicable method of stem cell administration, within a time frame that would be reasonable for clinicians and patient’s suffering traumatic brain injury.

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