PMID- 29963009 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200929 IS - 1664-2295 (Print) IS - 1664-2295 (Electronic) IS - 1664-2295 (Linking) VI - 9 DP - 2018 TI - Umbilical Cord-Derived Mesenchymal Stromal Cells Contribute to Neuroprotection in Neonatal Cortical Neurons Damaged by Oxygen-Glucose Deprivation. PG - 466 LID - 10.3389/fneur.2018.00466 [doi] LID - 466 AB - Several studies have reported that human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) restore neurological damage in vivo through their secretion of paracrine factors. We previously found that UC-MSCs attenuate brain injury by secreting neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and hepatocyte growth factor (HGF). However, how these factors contribute to neuroprotection remains unknown. In this study, we aimed to investigate to what extent UC-MSC-derived HGF and BDNF contribute to neuroprotection using a Transwell co-culture system of neonatal cortical neurons damaged by oxygen-glucose deprivation. The influence of HGF and BDNF were determined by investigating neurons in both the presence and absence of UC-MSCs as these cells consistently secrete both factors and can be blocked by neutralizing antibodies. In the co-culture, UC-MSCs significantly improved neuronal injury, as indicated by an increase in immature neuron number, neurite outgrowth, and cell proliferation. Co-culture of damaged neurons with UC-MSCs also exhibited a reduction in the number of neurons displaying signs of apoptosis/necrosis. The neuroprotective actions of UC-MSCs were partially reverted by neutralizing antibodies. Together, our findings reveal that UC-MSC-secreted HGF and BDNF have neuroprotective effects on damaged neurons. Further studies should address the existence of other potential neurotrophic paracrine factors. FAU - Mukai, Takeo AU - Mukai T AD - Division of Molecular of Therapy, Center for Advanced Medical Research, Institute of Medical Science, University of Tokyo, Tokyo, Japan. AD - Department of Cell Processing and Transfusion, Institute of Medical Science, University of Tokyo, Tokyo, Japan. FAU - Tojo, Arinobu AU - Tojo A AD - Division of Molecular of Therapy, Center for Advanced Medical Research, Institute of Medical Science, University of Tokyo, Tokyo, Japan. AD - Department of Cell Processing and Transfusion, Institute of Medical Science, University of Tokyo, Tokyo, Japan. FAU - Nagamura-Inoue, Tokiko AU - Nagamura-Inoue T AD - Department of Cell Processing and Transfusion, Institute of Medical Science, University of Tokyo, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20180615 PL - Switzerland TA - Front Neurol JT - Frontiers in neurology JID - 101546899 PMC - PMC6013549 OTO - NOTNLM OT - brain derived neurotrophic factor OT - cerebral palsy OT - hepatocyte growth factor OT - mesenchymal stromal cell OT - neonatal encephalopathy OT - umbilical cord EDAT- 2018/07/03 06:00 MHDA- 2018/07/03 06:01 PMCR- 2018/06/15 CRDT- 2018/07/03 06:00 PHST- 2017/11/10 00:00 [received] PHST- 2018/05/31 00:00 [accepted] PHST- 2018/07/03 06:00 [entrez] PHST- 2018/07/03 06:00 [pubmed] PHST- 2018/07/03 06:01 [medline] PHST- 2018/06/15 00:00 [pmc-release] AID - 10.3389/fneur.2018.00466 [doi] PST - epublish SO - Front Neurol. 2018 Jun 15;9:466. doi: 10.3389/fneur.2018.00466. eCollection 2018.