| RRC ID |
37538
|
| 著者 |
Nishimura K, Doi D, Samata B, Murayama S, Tahara T, Onoe H, Takahashi J.
|
| タイトル |
Estradiol Facilitates Functional Integration of iPSC-Derived Dopaminergic Neurons into Striatal Neuronal Circuits via Activation of Integrin α5β1.
|
| ジャーナル |
Stem Cell Reports
|
| Abstract |
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 α5 is selectively expressed in striatal neurons that are innervated by midbrain dopaminergic (DA) neurons. In addition, we found that integrin α5β1 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 α5β1. 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.
|
| 巻・号 |
6(4)
|
| ページ |
511-524
|
| 公開日 |
2016-4-12
|
| DOI |
10.1016/j.stemcr.2016.02.008
|
| PII |
S2213-6711(16)00059-X
|
| PMID |
26997644
|
| PMC |
PMC4834042
|
| MeSH |
Aged
Animals
Cell Differentiation / drug effects
Cells, Cultured
Corpus Striatum / cytology
Dopaminergic Neurons / drug effects*
Dopaminergic Neurons / metabolism
Dopaminergic Neurons / transplantation
Estradiol / analogs & derivatives
Estradiol / pharmacology*
Female
Gene Expression Profiling / methods
HEK293 Cells
Humans
Induced Pluripotent Stem Cells / drug effects*
Induced Pluripotent Stem Cells / metabolism
Integrin alpha5beta1 / genetics
Integrin alpha5beta1 / metabolism*
Male
Methamphetamine
Mice, Inbred C57BL
Microscopy, Confocal
Nerve Net / drug effects
Nerve Net / metabolism
Neural Stem Cells / drug effects*
Neural Stem Cells / metabolism
Neural Stem Cells / transplantation
Oxidopamine
Parkinson Disease, Secondary / chemically induced
Parkinson Disease, Secondary / metabolism
Parkinson Disease, Secondary / therapy
Rats, Inbred F344
Reverse Transcriptase Polymerase Chain Reaction
Stem Cell Transplantation / methods
Transplantation, Heterologous
|
| IF |
6.032
|
| 引用数 |
8
|
|
WOS 分野
|
CELL & TISSUE ENGINEERING
CELL BIOLOGY
|
| リソース情報 |
| ラット |
F344-Il2rgem2Kyo (strainID=979) |
