Placental Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Myelin Regeneration in an Animal Model of Multiple Sclerosis

Kaitlin Clark, Sheng Zhang, Sylvain Barthe, Priyadarsini Kumar, Christopher Pivetti, Nicole Kreutzberg, Camille Reed, Yan Wang, Zachary Paxton, Diana Farmer, Fuzheng Guo, Aijun Wang

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Mesenchymal stem/stromal cells (MSCs) display potent immunomodulatory and regenerative capabilities through the secretion of bioactive factors, such as proteins, cytokines, chemokines as well as the release of extracellular vesicles (EVs). These functional properties of MSCs make them ideal candidates for the treatment of degenerative and inflammatory diseases, including multiple sclerosis (MS). MS is a heterogenous disease that is typically characterized by inflammation, demyelination, gliosis and axonal loss. In the current study, an induced experimental autoimmune encephalomyelitis (EAE) murine model of MS was utilized. At peak disease onset, animals were treated with saline, placenta-derived MSCs (PMSCs), as well as low and high doses of PMSC-EVs. Animals treated with PMSCs and high-dose PMSC-EVs displayed improved motor function outcomes as compared to animals treated with saline. Symptom improvement by PMSCs and PMSC-EVs led to reduced DNA damage in oligodendroglia populations and increased myelination within the spinal cord of treated mice. In vitro data demonstrate that PMSC-EVs promote myelin regeneration by inducing endogenous oligodendrocyte precursor cells to differentiate into mature myelinating oligodendrocytes. These findings support that PMSCs' mechanism of action is mediated by the secretion of EVs. Therefore, PMSC-derived EVs are a feasible alternative to cellular based therapies for MS, as demonstrated in an animal model of the disease.

Original languageEnglish (US)
JournalCells
Volume8
Issue number12
DOIs
StatePublished - Nov 23 2019

Keywords

  • extracellular vesicles
  • mesenchymal stromal cells
  • multiple sclerosis
  • myelin regeneration
  • oligodendrocyte precursor cells

ASJC Scopus subject areas

  • Medicine(all)

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