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Assessment of long-term safety and efficacy of intranasal mesenchymal stem cell treatment for neonatal brain injury in the mouse.


ABSTRACT:

Background

For clinical translation, we assessed whether intranasal mesenchymal stem cell (MSC) treatment after hypoxia-ischemia (HI) induces neoplasia in the brain or periphery at 14 mo. Furthermore, the long-term effects of MSCs on behavior and lesion size were determined.

Method

HI was induced in 9-d-old mice. Pups received an intranasal administration of 0.5?×?10(6) MSCs or vehicle at 10 d post-HI. Full macroscopical and microscopical pathological analysis of 39 organs per mouse was performed. Sensorimotor behavior was assessed in the cylinder-rearing test at 10 d, 28 d, 6 mo, and 9 mo. Cognition was measured with the novel object recognition test at 3 and 14 mo post-HI. Lesion size was determined by analyzing mouse-anti-microtubule-associated protein 2 (MAP2) and mouse-anti-myelin basic protein (MBP) staining at 5?wk and 14 mo.

Results

At 14 mo post-HI, we did not observe any neoplasia in the nasal turbinates, brain, or other organs of HI mice treated with MSCs. Furthermore, our results show that MSC-induced improvement of sensorimotor and cognitive function is long lasting. In contrast, HI-vehicle mice showed severe behavioral impairment. Recovery of MAP2- and MBP-positive area lasted up to 14 mo following MSC treatment.

Conclusion

Our results provide strong evidence of the long-term safety and positive effects of MSC treatment following neonatal HI in mice.

SUBMITTER: Donega V 

PROVIDER: S-EPMC4635434 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Assessment of long-term safety and efficacy of intranasal mesenchymal stem cell treatment for neonatal brain injury in the mouse.

Donega Vanessa V   Nijboer Cora H CH   van Velthoven Cindy T J CT   Youssef Sameh A SA   de Bruin Alain A   van Bel Frank F   Kavelaars Annemieke A   Heijnen Cobi J CJ  

Pediatric research 20150813 5


<h4>Background</h4>For clinical translation, we assessed whether intranasal mesenchymal stem cell (MSC) treatment after hypoxia-ischemia (HI) induces neoplasia in the brain or periphery at 14 mo. Furthermore, the long-term effects of MSCs on behavior and lesion size were determined.<h4>Method</h4>HI was induced in 9-d-old mice. Pups received an intranasal administration of 0.5 × 10(6) MSCs or vehicle at 10 d post-HI. Full macroscopical and microscopical pathological analysis of 39 organs per mou  ...[more]

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