Characterization of mesenchymal stem cells derived from patients with cerebellar ataxia: Downregulation of the anti-inflammatory secretome profile

Jong Heon Kim, Jin Han, Donggun Seo, Jong Hyuk Yoon, Dongyeong Yoon, Jungwan Hong, Sang Ryong Kim, Min Sung Kim, Tae Yong Lee, Kyung Suk Kim, Pan Woo Ko, Ho Won Lee, Kyoungho Suk

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Mesenchymal stem cell (MSC) therapy is a promising alternative approach for the treatment of neurodegenerative diseases, according to its neuroprotective and immunomodulatory potential. Despite numerous clinical trials involving autologous MSCs, their outcomes have often been unsuccessful. Several reports have indicated that MSCs from patients have low capacities in terms of the secretion of neurotrophic or anti-inflammatory factors, which might be associated with cell senescence or disease severity. Therefore, a new strategy to improve their capacities is required for optimal efficacy of autologous MSC therapy. In this study, we compared the secretory potential of MSCs among cerebellar ataxia patients (CA-MSCs) and healthy individuals (H-MSCs). Our results, including secretome analysis findings, revealed that CA-MSCs have lower capacities in terms of proliferation, oxidative stress response, motility, and immunomodulatory functions when compared with H-MSCs. The functional differences were validated in a scratch wound healing assay and neuron-glia co-cultures. In addition, the neuroprotective and immunoregulatory protein follistatin-like 1 (FSTL1) was identified as one of the downregulated proteins in the CA-MSC secretome, with suppressive effects on proinflammatory microglial activation. Our study findings suggest that targeting aspects of the downregulated anti-inflammatory secretome, such as FSTL1, might improve the efficacy of autologous MSC therapy for CA.

Original languageEnglish
Article number212
JournalCells
Volume9
Issue number1
DOIs
StatePublished - Jan 2020

Keywords

  • Antiinflammation
  • Cerebellar ataxia
  • Mesenchymal stem cells

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