Mitochondrial dysfunction of immortalized human adipose tissue-derived mesenchymal stromal cells from patients with Parkinson's disease.
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.
Department of Neurosurgery, Seoul National University College of Medicine, Seoul 110-744, Korea. ; Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Korea. ; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-744, Korea.
Hyo Eun
HE
Moon
Department of Brain & Cognitive Sciences, College of Pharmacy, Brain Disease Research Institute, Ewha Woman's University, Seoul 120-750, Korea.
Seung Hee
SH
Yoon
Department of Biochemistry, Inha University School of Medicine, Incheon 402-751, Korea.
Yong Suk
YS
Hur
Department of Neurosurgery, Seoul National University College of Medicine, Seoul 110-744, Korea. ; Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Korea. ; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-744, Korea.
Hyung Woo
HW
Park
Department of Brain & Cognitive Sciences, College of Pharmacy, Brain Disease Research Institute, Ewha Woman's University, Seoul 120-750, Korea.
Ji Young
JY
Ha
Department of Brain & Cognitive Sciences, College of Pharmacy, Brain Disease Research Institute, Ewha Woman's University, Seoul 120-750, Korea.
Kyung-Hee
KH
Kim
Department of Brain & Cognitive Sciences, College of Pharmacy, Brain Disease Research Institute, Ewha Woman's University, Seoul 120-750, Korea.
Jung Hee
JH
Shim
Department of Biochemistry, Inha University School of Medicine, Incheon 402-751, Korea.
Seung Hyun
SH
Yoo
Department of Brain & Cognitive Sciences, College of Pharmacy, Brain Disease Research Institute, Ewha Woman's University, Seoul 120-750, Korea.
Jin H
JH
Son
Department of Neurosurgery, Seoul National University College of Medicine, Seoul 110-744, Korea. ; Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Korea. ; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-744, Korea. ; Department of Neurosurgery, Mayo Clinic, USA.
Seung Leal
SL
Paek
Department of Neurosurgery, Seoul National University College of Medicine, Seoul 110-744, Korea.
In Keyoung
IK
Kim
Department of Neurosurgery, Seoul National University College of Medicine, Seoul 110-744, Korea.
Jae Ha
JH
Hwang
Department of Neurosurgery, Seoul National University College of Medicine, Seoul 110-744, Korea.
Dong Gyu
DG
Kim
Department of Neurology, Seoul National University College of Medicine, Seoul 110-744, Korea.
Han-Joon
HJ
Kim
Department of Neurology, Seoul National University College of Medicine, Seoul 110-744, Korea.
Beom Seok
BS
Jeon
Department of Laboratory Medicine, Seoul National University Hospital, Seoul 110-744, Korea.
Sung Sup
SS
Park
Department of Neurosurgery, Seoul National University College of Medicine, Seoul 110-744, Korea. ; Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Korea. ; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-744, Korea.
Sun Ha
SH
Paek
Parkinson's disease; diagnosis; hAD-MSC; hTERT; immortalization