RRC ID 37538
Author Nishimura K, Doi D, Samata B, Murayama S, Tahara T, Onoe H, Takahashi J.
Title Estradiol Facilitates Functional Integration of iPSC-Derived Dopaminergic Neurons into Striatal Neuronal Circuits via Activation of Integrin α5β1.
Journal 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.
Volume 6(4)
Pages 511-524
Published 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
Times Cited 8
Rats F344-Il2rgem2Kyo (strainID=979)