Amniotic membranes (AM) have anti-fibrotic activity. Exosomes (nano-sized vesicles) function as conduits for intercellular transfer and contain all the necessary components to induce the resolution of fibrosis. In this study, we tested the hypothesis that the anti-fibrotic activity of AM is mediated by exosomes. AM-derived exosomes or amniotic stromal cell-derived exosomes were isolated and characterized. Anti-fibrotic activity of exosomes was evaluated using human hepatic stellate cells (LX-2), an in vitro model of fibrosis. Exosomes isolated from AM tissue-conditioned media had an average size of 75 nm. Exosomes significantly inhibited the proliferation of TGFβ1-activated LX-2 but had no effect on the proliferation of non-activated LX-2 cells. Exosomes also reduced the migration of LX-2 in a scratch wound assay. Furthermore, exosomes reduced the gene expression of pro-fibrotic markers such as COL1A1, ACTA, and TGFβ1 in LX-2 cells. Interestingly, exosomes isolated from AM tissue under hypoxic conditions seemed to show a stronger anti-fibrotic activity than exosomes isolated from tissue under normoxic conditions. Exosomes released by in vitro cultured AM stromal cells were smaller in size compared with tissue exosomes and also showed anti-fibrotic activity on LX-2 cells. In conclusion, AM-tissue-released exosomes contribute to the anti-fibrotic activity of AM. This is the first report of isolation, characterization, and functional evaluation of exosomes derived from amniotic tissues with the direct comparison between tissue-derived exosomes and cultured cell-derived exosomes.
Enhanced Recovery After Surgery (ERAS) is a multidisciplinary approach to improve patient care using a combination of evidence-based methods. The interventions found in ERAS protocols are based on the rationale that patient outcomes can be improved by controlling pain and optimizing fluid administration, early ambulation, and nutrition to prevent catabolism and immune dysfunction. There are different ERAS protocols available for different surgical fields with the shared goal of minimizing physiological patient stress [1]. ERAS protocols can be partitioned into their pre-operative, intra-operative, and post-operative management. The preoperative component of ERAS protocols includes pre-emptive analgesia (e.g. gabapentin/ pregabalin, acetaminophen), nutrition and fasting optimization, and patient education. The intraoperative component of ERAS protocols focuses on the choice of anaesthetic agents for induction and maintenance (e.g. propofol, ketamine, use of total intravenous anaesthesia [TIVA] vs. inhaled anaesthetics), and utilization of non-opioid analgesics (e.g. ketorolac, lidocaine). The post-operative component of ERAS protocols addresses early ambu-
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