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Stem Cell-Derived Exosomes Protect Astrocyte Cultures From in vitro Ischemia and Decrease Injury as Post-stroke

Xiaoyun Sun1, Ji-Hye Jung2,3, Oiva Arvola1

  • 1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States.

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|September 26, 2019
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Summary

Neural stem cell-derived exosomes protect brain cells from ischemic injury. Intravenous exosome therapy after stroke significantly reduced infarct volume in mice, suggesting a potential new treatment for stroke patients.

Keywords:
MCAOcerebral ischemiagliaiCMiPSCpluripotent

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Area of Science:

  • Neuroscience
  • Regenerative Medicine
  • Cell Biology

Background:

  • Ischemic stroke causes significant neuronal and glial cell death.
  • Exosomes, small extracellular vesicles, carry therapeutic molecules and have shown potential in regenerative medicine.
  • Stem cell-derived exosomes are being investigated for their protective effects in various diseases.

Purpose of the Study:

  • To evaluate the neuroprotective efficacy of exosomes derived from human and mouse stem cells.
  • To assess the protective effects of these exosomes against in vitro ischemia in astrocyte and neuronal cultures.
  • To determine the in vivo efficacy of neural stem cell (NSC)-derived exosomes in a mouse model of ischemic stroke.

Main Methods:

  • Exosomes were isolated and purified from human induced pluripotent stem cell-derived cardiomyocyte (iCM) and mouse neural stem cell (NSC) cultures.
  • Exosomes were applied to primary mouse astrocyte and neuronal cultures subjected to oxygen-glucose deprivation (OGD).
  • NSC-derived exosomes were administered intravenously to mice following middle cerebral artery occlusion (MCAO) to assess in vivo stroke protection.

Main Results:

  • NSC-derived exosomes significantly protected astrocytes from OGD-induced cell death.
  • Human iCM-derived exosomes and NSC-derived exosomes provided modest protection to astrocytes and neurons, respectively.
  • Intravenous administration of NSC-derived exosomes post-MCAO resulted in significantly reduced infarct volumes and improved outcomes in mice.

Conclusions:

  • Exosomes derived from mouse NSCs demonstrate significant neuroprotective capabilities against experimental stroke.
  • The protective mechanism may involve the preservation of astrocyte function.
  • Intravenous NSC-derived exosome therapy presents a promising novel adjuvant treatment for the acute phase of ischemic stroke.