Takahashi Haruka, Ishikawa Hiroshi, Tanaka Akira
Oral and Maxillofacial Surgery, Field of Oral and Maxillofacial Surgery and Systemic Medicine, Course of Clinical Science, Nippon Dental University Graduate School of Life Dentistry at Niigata, 1-8 Hamaura-cho, Chuo-ku, Niigata, 951-8580, Japan.
Department of NDU Life Sciences, Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan.
Hum Cell. 2017 Apr;30(2):60-71. doi: 10.1007/s13577-017-0160-3. Epub 2017 Feb 16.
The purpose of this study was to evaluate the utility of human adipose stem cells derived from the buccal fat pad (hBFP-ASCs) for nerve regeneration. Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons. PD is a candidate disease for cell replacement therapy because it has no fundamental therapeutic methods. We examined the properties of neural-related cells induced from hBFP-ASCs as a cell source for PD treatment. hBFP-ASCs were cultured in neurogenic differentiation medium for about 2 weeks. After the morphology of hBFP-ASCs changed to neural-like cells, the medium was replaced with neural maintenance medium. Cells differentiated from hBFP-ASCs showed neuron-like structures and expressed neuron markers (β3-tubulin, neurofilament 200, and microtubule-associated protein 2), an astrocyte marker (glial fibrillary acidic protein), or dopaminergic neuron-related marker (tyrosine hydroxylase). Induced neural cells were transplanted into a 6-hydroxydopamine (6-OHDA)-lesioned rat hemi-parkinsonian model. At 4 weeks after transplantation, 6-OHDA-lesioned rats were subjected to apomorphine-induced rotation analysis. The transplanted cells survived in the brain of rats as dopaminergic neural cells. No tumor formation was found after cell transplantation. We demonstrated differentiation of hBFP-ASCs into neural cells, and that transplantation of these neural cells improved the symptoms of model rats. Our results suggest that neurons differentiated from hBFP-ASCs would be applicable to cell replacement therapy of PD.
本研究的目的是评估源自颊脂垫的人脂肪干细胞(hBFP-ASCs)在神经再生中的效用。帕金森病(PD)是一种以多巴胺能神经元进行性死亡为特征的神经退行性疾病。由于PD没有根本性的治疗方法,它是细胞替代疗法的候选疾病。我们检测了从hBFP-ASCs诱导产生的神经相关细胞作为PD治疗细胞来源的特性。将hBFP-ASCs在神经源性分化培养基中培养约2周。当hBFP-ASCs的形态转变为神经样细胞后,将培养基换成神经维持培养基。从hBFP-ASCs分化而来的细胞呈现出神经元样结构,并表达神经元标志物(β3-微管蛋白、神经丝200和微管相关蛋白2)、星形胶质细胞标志物(胶质纤维酸性蛋白)或多巴胺能神经元相关标志物(酪氨酸羟化酶)。将诱导产生的神经细胞移植到6-羟基多巴胺(6-OHDA)损伤的大鼠半帕金森病模型中。移植后4周,对6-OHDA损伤的大鼠进行阿扑吗啡诱导的旋转分析。移植的细胞作为多巴胺能神经细胞在大鼠脑中存活。细胞移植后未发现肿瘤形成。我们证明了hBFP-ASCs可分化为神经细胞,并且这些神经细胞的移植改善了模型大鼠的症状。我们的结果表明,从hBFP-ASCs分化而来的神经元可应用于PD的细胞替代治疗。