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云南省第一人民医院
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.
基金:
Research
Fund for Doctor Innovation of Beijing Union
Medical College; Science and Technology Project
of Yunnan Province (2012AE001, 2007C0012Z);
National Natural Science Foundation of China
(30971003).
第一作者机构:[1]Institute of Medical Biology, Peking Union Medical College, Chinese Academy of Medical Science, Kunming, China,
通讯作者:
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
推荐引用方式(GB/T 7714):
Zhou Yan,Sun Maosheng,Li Hongjun,et al.Recovery of behavioral symptoms in hemi-parkinsonian rhesus monkeys through combined gene and stem cell therapy[J].CYTOTHERAPY.2013,15(4):467-480.doi:10.1016/j.jcyt.2013.01.007.
APA:
Zhou, Yan,Sun, Maosheng,Li, Hongjun,Yan, Min,He, Zhanlong...&Lu, Shuaiyao.(2013).Recovery of behavioral symptoms in hemi-parkinsonian rhesus monkeys through combined gene and stem cell therapy.CYTOTHERAPY,15,(4)
MLA:
Zhou, Yan,et al."Recovery of behavioral symptoms in hemi-parkinsonian rhesus monkeys through combined gene and stem cell therapy".CYTOTHERAPY 15..4(2013):467-480