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Recovery of behavioral symptoms in hemi-parkinsonian rhesus monkeys through combined gene and stem cell therapy

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机构: [1]Institute of Medical Biology, Peking Union Medical College, Chinese Academy of Medical Science, Kunming, China, [2]Kunming Institute of Zoology, CAS, Kunming, China, [3]First People’s Hospital of Yunnan Province, Kunming, China
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关键词: differentiation LMX1A Neurturin neuron Parkinson disease Rhesus adipose stem cells (rASCs) TH

摘要:
Background aims. The use of adipose mesenchymal stromal cells (ASCs) in cellular and genic therapy has attracted considerable attention as a possible treatment for neurodegenerative disorders, including Parkinson disease. However, the effects of gene therapy combined with intracerebral cell transplantation have not been well defined. Recent studies have demonstrated the respective roles of LIM homeobox transcription factor 1, alpha (LMX1A) and Neurturin (NTN) in the commitment of embryonic stem cells (ESCs) to a midbrain dopaminergic neuronal fate and the commitment of mesenchymal stromal cells to cells supporting the nutrition and protection of neurons. Methods. We investigated a novel in vitro neuronal differentiation strategy with the use of LMX1A and Neurturin. We were able to elicit a neural phenotype regarding cell morphology, specific gene/protein expression and physiological function. Neuronal-primed ASCs derived from rhesus monkey (rASCs) combined with adenovirus containing NTN and tyrosine hydroxylase (TH) (Ad-NTN-TH) were implanted into the striatum and substantia nigra of methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-lesioned hemi-parkinsonian rhesus monkeys. Monkeys were monitored with the use of behavioral tests and health measures until the fourth month after implantation. Results. The differentiated cells transcribed and expressed a variety of dopaminergic neuron-specific genes involved in the SHH/LMX1A pathway. Single-photon emission computed tomography analysis and postmortem analysis revealed that the grafting of rASCs combined with Ad-NTN-TH had neuroprotective effects compared with Ad-NTN-TH or rASCs alone. Behavioral measures demonstrated autograft survival and symptom amelioration. Conclusions. These findings may lead to cellular sources for autologous transplantation of Parkinson disease. Combined transplantation of Ad-NTN-TH and induced rASCs expressing LMX1A and NTN may be a better therapy candidate for the treatment of Parkinson disease.

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出版当年[2013]版:
大类 | 3 区 医学
小类 | 3 区 生物工程与应用微生物 3 区 血液学 3 区 医学:研究与实验 4 区 细胞与组织工程 4 区 细胞生物学
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 生物工程与应用微生物 3 区 细胞生物学 3 区 血液学 3 区 医学:研究与实验 4 区 细胞与组织工程
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出版当年[2012]版:
Q2 MEDICINE, RESEARCH & EXPERIMENTAL Q2 HEMATOLOGY Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q3 CELL BIOLOGY Q3 CELL & TISSUE ENGINEERING
最新[2023]版:
Q1 HEMATOLOGY Q2 CELL BIOLOGY Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q2 CELL & TISSUE ENGINEERING Q2 MEDICINE, RESEARCH & EXPERIMENTAL

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第一作者机构: [1]Institute of Medical Biology, Peking Union Medical College, Chinese Academy of Medical Science, Kunming, China,
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通讯机构: [1]Institute of Medical Biology, Peking Union Medical College, Chinese Academy of Medical Science, Kunming, China, [*1]Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, China
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