Cells. 2019 Nov 23;8(12)

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

Clark K1,2, Zhang S2, Barthe S1, Kumar P1,2, Pivetti C1,2, Kreutzberg N1, Reed C1, Wang Y2, Paxton Z1, Farmer D1,2, Guo F2, Wang A1,2,3.

Author information
1
Department of Surgery, School of Medicine, University of California Davis, Sacramento, CA 95817, USA.
2
Shriner's Hospitals for Children, Northern California, Sacramento, CA 95817, USA.
3
Department of Biomedical Engineering, University of California Davis, Davis, CA 95616, USA.
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.

KEYWORDS:
extracellular vesicles; mesenchymal stromal cells; multiple sclerosis; myelin regeneration; oligodendrocyte precursor cells

https://www.ncbi.nlm.nih.gov/pubmed/31771176