A1-Exosomes Suppress Systemic Inflammation and Neuroinflammation Induced by LPS in Mice

QISONG LIU; GUSTAVO YANNARELLI; NATALIA PACIENZA; DARWIN J. PROCKOP; DONG-KI KIM; SHUBIN FANG

Clearwater Beach

Conferencia; The American Society for Neural Therapy and Repair (INTR-15); 2018

The American Society for Neural Therapy and Repair

Neuroinflammation is an important component of many diseases of the brain. Recently there has been great interest in the therapeutic potential of the small endometrium-derived vesicles loosely defined as exosomes. We and others previously demonstrated that some preparations of exosomes produced beneficial effects in several models of brain injury. Here we examined the model for inflammation induced by systemic administration of LPS to mice. We first established a low dose of LPS that at 2 to 6 hours produced increases of pro-inflammatory cytokines in multiple tissues, including the brain. We then tested the effects of exosomes that we had previously isolated with a chromatographic protocol from the medium of mesenchymal stem/stromal cells cultured under defined conditions. The exosomes were anti-inflammatory by several criteria and to distinguish them from other exosomes, we referred to them as A1-exosomes. Intravenously administered A1-exosomes suppressed pro-inflammatory cytokines in multiple tissues, including the hippocampus and cortex. Exosomes pre-labeled with dye were found in microglia, indicating they had crossed the blood-brain barrier (BBB). In contrast, intravenous administration of 1.2 mg/kg dexamethasone decreased pro-inflammatory cytokines in spleen of LPS-treated mice but not in hippocampus or cortex. The results support previous indications that intravenously administered exosomes may be a more effective therapy for neuroinflammation than drugs and other agents that were tested in the past and that do not effectively cross the BBB.