Journal
STEM CELL REPORTS
Volume 6, Issue 4, Pages 511-524Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2016.02.008
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Funding
- Ichiro Kanehara Foundation
- Network Program for Realization of Regenerative Medicine from the Japan Science and Technology Agency
- Intramural Research Grant for Neurological and Psychiatric Disorders from the National Center of Neurology and Psychiatry [24-9]
- JSPS DC2 fellowship [14J02729]
- [26861146]
- Grants-in-Aid for Scientific Research [26861146, 14J02729] Funding Source: KAKEN
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For cell transplantation therapy for Parkinson's disease (PD) to be realized, the grafted neurons should be integrated into the host neuronal circuit to restore the lost neuronal function. Here, using wheat-germ agglutinin-based transsynaptic tracing, we show that integrin alpha 5 is selectively expressed in striatal neurons that are innervated by midbrain dopaminergic (DA) neurons. In addition, we found that integrin alpha 5 beta 1 was activated by the administration of estradiol-2-benzoate (E2B) in striatal neurons of adult female rats. Importantly, we observed that the systemic administration of E2B into hemi-parkinsonian rat models facilitates the functional integration of grafted DA neurons derived from human induced pluripotent stem cells into the host striatal neuronal circuit via the activation of integrin a5b1. Finally, methamphetamine-induced abnormal rotation was recovered earlier in E2B-administered rats than in rats that received other regimens. Our results suggest that the simultaneous administration of E2B with stem cell-derived DA progenitors can enhance the efficacy of cell transplantation therapy for PD.
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