Abstract

OBJECTIVE:

We investigated the feasibility and efficacy of bone marrow mesenchymal stem cells (BMSCs)-derived neural stem-like cells (MS-NSCs) therapy on injured brain in rats after severe acute carbon monoxide (CO) poisoning.

DESIGN:

Controlled animal study.

SETTING:

Research laboratory of a university hospital.

SUBJECTS:

Sprague-Dawley rats weighing 230 +/- 20 g and 90 +/- 10 g.

INTERVENTIONS:

The rats were exposed to 1000 ppm CO in air for 40 minutes and then to 3000 ppm for another 20 minutes until they lost consciousness. Approximately 7 x 10 allogeneic BMSCs or MS-NSCs labeled with BrdU were infused into the poisoned rats via the internal carotid after a 24-hour resuscitation. The rats with and without CO poisoning were used as placebo and sham controls, respectively.

MEASUREMENTS AND MAIN RESULTS:

The neurologic and cognitive functions were evaluated by Neurologic Severity Scores and Morris water maze tests. Examinations with immunohistochemistry, myelin, and hematoxylin-eosin staining were made to assess cerebral structure after 5 weeks. Histologically, the compactness and arrangement of the insulted white matter were improved by the cellular treatments. The transplanted MS-NSCs were positive for microtubule-associated protein 2 in hippocampus, 84.6% +/- 5.6%, and for glial fibrillary acidic protein in subventricular white matter and hippocampus, 32.2% +/- 2.5% and 9.7% +/- 1.2%, respectively, although the MS-NSCs group showed a larger fraction in the expression of the above markers in corresponding domains compared with the BMSCs group. The MS-NSCs also displayed a higher survival rate than BMSCs in most domains of diffusively injured brain, leading to a better improvement in the Morris water maze test (p < 0.05).

CONCLUSIONS:

The stem cell-based therapy could be advantageous for improving the structure and function of injured brain in rats after severe acute CO poisoning, indicating the potential use as a novel approach for severely CO-poisoned patients with delayed neurologic sequelae. Furthermore, MS-NSCs may render better therapeutic effects after neurologic injury than untreated BMSCs.