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Original Article

Exp Neurobiol 2013; 22(4): 283-300

Published online December 30, 2013

© The Korean Society for Brain and Neural Sciences

Mitochondrial Dysfunction of Immortalized Human Adipose Tissue-Derived Mesenchymal Stromal Cells from Patients with Parkinson’s Disease

Hyo Eun Moon1,2,3, Seung Hee Yoon5, Yong Suk Hur6, Hyung Woo Park1,2,3, Ji Young Ha5, Kyung-Hee Kim5, Jung Hee Shim5, Seung Hyun Yoo6, Jin H. Son5, Seung Leal Paek1,2,3,8, In Keyoung Kim1, Jae Ha Hwang1, Dong Gyu Kim1, Han-Joon Kim4, Beom Seok Jeon4, Sung Sup Park7 and Sun Ha Paek1,2,3*

1Department of Neurosurgery, 2Cancer Research Institute, 3Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, 4Department of Neurology, Seoul National University College of Medicine, Seoul 110-744, 5Department of Brain & Cognitive Sciences, College of Pharmacy, Brain Disease Research Institute, Ewha Woman’s University, Seoul 120-750, 6Department of Biochemistry, Inha University School of Medicine, Incheon 402-751, 7Department of Laboratory Medicine, Seoul National University Hospital, Seoul 110-744, Korea, 8Department of Neurosurgery, Mayo Clinic, USA

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-2072-3993, FAX: 82-2-744-8459

Received: November 12, 2013; Revised: November 22, 2013; Accepted: November 22, 2013


Mitochondrial dysfunction in dopaminergic neurons of patients with idiopathic and familial Parkinson's disease (PD) is well known although the underlying mechanism is not clear. We established a homogeneous population of human adipose tissue-derived mesenchymal stromal cells (hAD-MSCs) from human adult patients with early-onset hereditary familial Parkin-defect PD as well as late-onset idiopathic PD by immortalizing cells with the hTERT gene to better understand the underlying mechanism of PD. The hAD-MSCs from patients with idiopathic PD were designated as "PD", from patients with Parkin-defect PD as "Parkin" and from patients with pituitary adenomas as "non-PD" in short. The pGRN145 plasmid containing hTERT was introduced to establish telomerase immortalized cells. The established hTERT-immortalized cell lines showed chromosomal aneuploidy sustained stably over two-years. The morphological study of mitochondria in the primary and immortalized hAD-MSCs showed that the mitochondria of the non-PD were normal; however, those of the PD and Parkin were gradually damaged. A striking decrease in mitochondrial complex I, II, and IV activities was observed in the hTERT-immortalized cells from the patients with idiopathic and Parkin-defect PD. Comparative Western blot analyses were performed to investigate the expressions of PD specific marker proteins in the hTERT-immortalized cell lines. This study suggests that the hTERT-immortalized hAD-MSC cell lines established from patients with idiopathic and familial Parkin-defect PD could be good cellular models to evaluate mitochondrial dysfunction to better understand the pathogenesis of PD and to develop early diagnostic markers and effective therapy targets for the treatment of PD.

Keywords: hTERT, hAD-MSC, immortalization, Parkinson’s disease, diagnosis