Implantation of glial cell line-derived neurotrophic factor-expressing adipose tissue-derived stromal cells in a rat Parkinson’s disease model

ABSTRACT

In previous studies, the effects of glial cell line-derived neurotrophic factor (GDNF) expressing adipose tissue-derived stromal cells (ADSCs) on Parkinson’s disease (PD) models have been studied but have not been elucidated. The present study aims to investigate this phenomenon and trace their differentiation in vivo. In our study, ADSCs were harvested from adult Sprague-Dawley rats, then genetically modified into GDNF-expressing system by lentivirus. The secretion of GDNF from the transduced cells was titrated by enzyme-linked immunosorbent assay (ELISA). Cellular differentiation in vitro was observed after induction. To examine survival and differentiation in vivo, they were injected into the striatum of 6-hydroxydopamine-lesioned rats, whose apomorphine-induced rotations were examined 2, 7, 14 and 21d after grafting. It’s found that GDNF-expressing ADSCs can differentiate into neuron-like cells in vitro. Moreover, engrafted GDNF-expressing ADSCs survived at least 90 days post-grafting and differentiated into dopaminergic neuron-like cells. Most importantly, these cells drastically improved the clinical symptoms of PD rats. In conclusion, ADSCs can be efficiently engineered by lentivirus system and deliver a therapeutic level of the transgene to target tissues. GDNF-ADSCs can improve behavior phenotype in the rat PD model. Moreover, ADSCs is a more readily available source of dopaminergic neurons, though a more effective procedure needs to be developed to enrich the number of differentiation.

KEYWORDS:

• Adipose tissue-derived stromal cells
• differentiation
• dopaminergic neuron
• lentivirus
• Parkinson’s disease

Acknowledgments

We gratefully acknowledge Mr. Xianyang Zhang (LSU Health Sciences Center, Louisiana, USA) for his invaluable suggestions on experimental techniques.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by grant [No. 30600577] from the National Natural Science Foundations of China, grant [No. 201740026] from Shanghai Health Planning Commission, and grant [No. 19140900105] from Shanghai Committee of Science and Technology.