graded spinal cord injury model in a nonhuman primate and stem cells transplants in the model

[Wise Young]

For many years, there was no well-established monkey spinal cord injury model. This study from Keio University reports a graded cervical spinal cord contusion model in the marmoset and then treatment of this model with human neural progenitor cells. Apparently, the cells survived and differentiated into neurons, astrocytes, and oligodendroglia. The acutely transplanted cells also appear to reduce cavity sizes at the injury site, along with improved grip and more spontaneous motor activity in the transplanted animals, compared to untransplanted controls.

Iwanami A, Yamane J, Katoh H, Nakamura M, Momoshima S, Ishii H, Tanioka Y, Tamaoki N, Nomura T, Toyama Y and Okano H (2005). Establishment of graded spinal cord injury model in a nonhuman primate: The common marmoset. J Neurosci Res 80: 172-181. Most previous studies on spinal cord injury (SCI) have used rodent models. Direct extrapolation of the results obtained in rodents to clinical cases is difficult, however, because of neurofunctional and anatomic differences between rodents and primates. In the present study, the development of histopathologic changes and functional deficits were assessed quantitatively after mild, moderate, and severe spinal cord contusive injuries in common marmosets. Contusive SCI was induced by dropping one of three different weights (15, 17, or 20 g) at the C5 level from a height of 50 mm. Serial magnetic resonance images showed significant differences in the intramedullary T1 low signal and T2 high signal areas among the three groups. Quantitative histologic analyses revealed that the number of motor neurons, the myelinated areas, and the amounts of corticospinal tract fibers decreased significantly as the injury increased in severity. Motor functions were evaluated using the following tests: original behavioral scoring scale, measurements of spontaneous motor activity, bar grip test, and cage-climbing test. Significant differences in all test results were observed among the three groups. Spontaneous motor activities at 10 weeks after injury were closely correlated with the residual myelinated area at the lesion epicenter. The establishment of a reliable nonhuman primate model for SCI with objective functional evaluation methods should become an essential tool for future SCI treatment studies. Quantitative behavioral and histopathologic analyses enabled three distinct grades of injury severity (15-g, 17-g, and 20-g groups) to be characterized with heavier weights producing more serious injuries, and relatively constant behavioral and histopathologic outcomes. (c) 2005 Wiley-Liss, Inc. Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan.

Iwanami A, Kaneko S, Nakamura M, Kanemura Y, Mori H, Kobayashi S, Yamasaki M, Momoshima S, Ishii H, Ando K, Tanioka Y, Tamaoki N, Nomura T, Toyama Y and Okano H (2005). Transplantation of human neural stem cells for spinal cord injury in primates. J Neurosci Res 80: 182-190. Recent studies have shown that delayed transplantation of neural stem/progenitor cells (NSPCs) into the injured spinal cord can promote functional recovery in adult rats. Preclinical studies using nonhuman primates, however, are necessary before NSPCs can be used in clinical trials to treat human patients with spinal cord injury (SCI). Cervical contusion SCIs were induced in 10 adult common marmosets using a stereotaxic device. Nine days after injury, in vitro-expanded human NSPCs were transplanted into the spinal cord of five randomly selected animals, and the other sham-operated control animals received culture medium alone. Motor functions were evaluated through measurements of bar grip power and spontaneous motor activity, and temporal changes in the intramedullary signals were monitored by magnetic resonance imaging. Eight weeks after transplantation, all animals were sacrificed. Histologic analysis revealed that the grafted human NSPCs survived and differentiated into neurons, astrocytes, and oligodendrocytes, and that the cavities were smaller than those in sham-operated control animals. The bar grip power and the spontaneous motor activity of the transplanted animals were significantly higher than those of sham-operated control animals. These findings show that NSPC transplantation was effective for SCI in primates and suggest that human NSPC transplantation could be a feasible treatment for human SCI. (c) 2005 Wiley-Liss, Inc. Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan.