Therapeutic Effect of Human Adipocyte-derived Stem Cell-derived Exosomes on a Transgenic Mouse Model of Parkinson's Disease

Lung Chan; Wayne Hsu; Kai-Yun Chen; Weu Wang; Yi-Chieh Hung; Chien-Tai Hong

doi:10.21873/invivo.13300

Therapeutic Effect of Human Adipocyte-derived Stem Cell-derived Exosomes on a Transgenic Mouse Model of Parkinson's Disease

In Vivo. 2023 Sep-Oct;37(5):2028-2038. doi: 10.21873/invivo.13300.

Authors

Lung Chan^#^{1

2

3}, Wayne Hsu^#⁴, Kai-Yun Chen⁵, Weu Wang^{4

6}, Yi-Chieh Hung^{7

8}, Chien-Tai Hong^{9

2

3}

Affiliations

¹ Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, R.O.C.
² Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.
³ Taipei Neuroscience Institute, Taipei Medical University, Taipei, Taiwan, R.O.C.
⁴ Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C.
⁵ Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, R.O.C.
⁶ Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.
⁷ Department of Neurosurgery, Chi-Mei Medical Center, Tainan, Taiwan, R.O.C.; ygmilloy@gmail.com.
⁸ Department of Recreation and Healthcare Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, R.O.C.
⁹ Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, R.O.C.; ct.hong@tmu.edu.tw.

^# Contributed equally.

Abstract

Background/aim: Stem cell therapy and regenerative medicine are promising for treating Parkinson's disease (PD) not only for the potential for cell replacement but also for the paracrine effect of stem cell secretion, especially proteins and nucleotide-enriched exosomes. This study investigated the neuroprotective effect of exosomes secreted from human adipocyte-derived stem cells (hADSCs) on PD.

Materials and methods: hADSCs were isolated from the visceral fat tissue of individuals without PD who underwent bariatric surgery and were validated using surface markers and differentiation ability. Exosomes were isolated from the culture medium of hADSCs through serial ultracentrifugation and validated. Condensed exosomes were administered intravenously to 12-week-old MitoPark mice, transgenic parkinsonism mouse model with conditional knockout of mitochondrial transcription factor A in dopaminergic neurons, monthly for 3 months. Motor function, gait, and memory were assessed monthly, and immunohistochemical analysis of neuronal and inflammatory markers was performed at the end of the experiments.

Results: The hADSC-derived exosome-treated mice exhibited better motor function in beam walking and gait analyses than did the untreated mice. In the novel object recognition tests, the exosome-treated mice retained better memory function. Immunohistochemical analysis revealed that although exosome treatment did not prevent the loss of dopaminergic neurons in the substantia nigra of mice, it down-regulated microglial activation and neuroinflammation in the midbrain.

Conclusion: hADSC-derived exosomes were neuroprotective in this in vivo mouse model of PD, likely because of their anti-inflammatory effect. Use of hADSC-derived exosomes may offer several beneficial effects in stem cell therapy. Since they can also be produced at an industrial level, they are a promising treatment option for PD and other neurodegenerative diseases.

Keywords: Parkinson’s disease; adipocyte-derived stem cells; exosome; inflammation.

MeSH terms

Adipocytes
Animals
Exosomes* / metabolism
Humans
Mice
Mice, Transgenic
Parkinson Disease* / genetics
Parkinson Disease* / metabolism
Parkinson Disease* / therapy
Stem Cells / metabolism