Exp Neurobiol.  2013 Dec;22(4):283-300. 10.5607/en.2013.22.4.283.

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

• Moon HE
• Yoon SH
• Hur YS
• Park HW
• Ha JY
• Kim KH
• Shim JH
• Yoo SH
• Son JH
• Paek SL
• Kim IK
• Hwang JH
• Kim DG
• Kim HJ
• Jeon BS
• Park SS
• Paek SH

• KMID: 2284632
• DOI: http://doi.org/10.5607/en.2013.22.4.283

Abstract

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.

Keyword

hTERT; hAD-MSC; immortalization; Parkinson's disease; diagnosis

MeSH Terms

Adult
Aneuploidy
Blotting, Western
Cell Line
Diagnosis
Dopaminergic Neurons
Humans*
Mesenchymal Stromal Cells*
Mitochondria
Parkinson Disease*
Pituitary Neoplasms
Plasmids
Strikes, Employee
Telomerase
Telomerase