4.6 Article

Amnion-Derived Multipotent Progenitor Cells Suppress Experimental Optic Neuritis and Myelitis

Journal

NEUROTHERAPEUTICS
Volume 18, Issue 1, Pages 448-459

Publisher

SPRINGER
DOI: 10.1007/s13311-020-00949-9

Keywords

Neuroprotection; Multiple sclerosis; Experimental autoimmune encephalomyelitis; Optic neuritis; Retinal ganglion cell; Amnion-derived multipotent progenitor cell; ST266

Funding

  1. NIH [EY019014, EY030163]
  2. Research to Prevent Blindness
  3. F. M. Kirby Foundation
  4. RWJ Harold Amos Faculty Development Award
  5. Noveome Biotherapeutics, Inc.
  6. NICHD

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This study demonstrates that systemically administered AMP cells can suppress optic neuritis and myelitis in EAE mice, potentially serving as a novel treatment for multiple sclerosis.
The human amnion has been used for decades in wound healing, particularly burns. Amnion epithelial cells (AECs) have been the focus of extensive research based on their possible pluripotent differentiation ability. A novel, cultured cell population derived from AECs, termed human amnion-derived multipotent progenitor (AMP) cells, secrete numerous cytokines and growth factors that enhance tissue regeneration and reduce inflammation. This AMP cell secretome, termed ST266, is a unique biological solution that accumulates in eyes and optic nerves following intranasal delivery, resulting in selective suppression of optic neuritis in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, but not myelitis at the administered dose. We tested the hypothesis that systemic AMP cell administration could suppress both optic neuritis and myelitis in EAE. Intravenous and intraperitoneal administration of AMP cells significantly reduced ascending paralysis and attenuated visual dysfunction in EAE mice. AMP cell treatment increased retinal ganglion cell (RGC) survival and decreased optic nerve inflammation, with variable improvement in optic nerve demyelination and spinal cord inflammation and demyelination. Results show systemic AMP cell administration inhibits RGC loss and visual dysfunction similar to previously demonstrated effects of intranasally delivered ST266. Importantly, AMP cells also promote neuroprotective effects in EAE spinal cords, marked by reduced paralysis. Protective effects of systemically administered AMP cells suggest they may serve as a potential novel treatment for multiple sclerosis.

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