PMID- 29251705 OWN - NLM STAT- MEDLINE DCOM- 20190304 LR - 20190304 IS - 2163-0763 (Electronic) IS - 2163-0755 (Linking) VI - 84 IP - 5 DP - 2018 May TI - Human adipose-derived stem cell treatment modulates cellular protection in both in vitro and in vivo traumatic brain injury models. PG - 745-751 LID - 10.1097/TA.0000000000001770 [doi] AB - BACKGROUND: Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the civilian population. The purpose of this study was to examine the effect(s) of adipose-derived stem cell (ASC) treatment on cellular and functional recovery in TBI via both in vitro and in vivo methods. METHODS: Cultured neuroblastoma cells, SH-SY5Y, were scratched to mimic TBI in an in vitro model. The effect of ASC-conditioned medium (CM) on cell death, mitochondrial function, and expression of inflammatory cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin 1beta [IL-1beta], and IL-6), as well as apoptosis marker FAS, was measured. In our in vivo model, Sprague-Dawley rats underwent TBI via a frontal, closed-head injury model. Animals randomly received either intravenous human-derived ASCs or intravenous saline within 3 hours of injury and were compared with a sham group. Functional recovery was evaluated via accelerating Rotarod method. On post-TBI Day 3, brain tissue was harvested and assessed for cellular damage via enzyme-linked immunosorbent assay for TNF-alpha, as well as immunohistochemical staining for beta-amyloid precursor protein (beta-APP). RESULTS: Our in vitro data show that ASC treatment imparted reduced cell death (ratio to control: 1.21 +/- 0.066 vs. 1.01 +/- 0.056, p = 0.017), increased cell viability (ratio to control: 0.86 +/- 0.009 vs. 1.09 +/- 0.01, p = 0.0001), increased mitochondrial function (percentage of control: 78 +/- 6% vs. 68 +/- 3%), and significantly decreased levels of inflammatory cytokine IL-1beta. In our in vivo study, compared with TBI alone, ASC-treated animals showed no difference in functional recovery, lower levels of expressed TNF-alpha (ratio to total protein, 0.47 +/- 0.01 vs. 0.67 +/- 0.04; p < 0.01), and lower levels of beta-amyloid precursor protein (fluorescence ratio, 0.43 +/- 0.05 vs. 0.69 +/- 0.03; p < 0.01). CONCLUSIONS: Adipose-derived stem cell treatment results in improved cell survival, decreased inflammatory marker release, and decreased evidence of neural injury. No difference in functional recovery was seen. These data suggest the potential for ASC treatment to aid in cellular protection and recovery in neural cells following TBI. FAU - Kappy, Nikolas S AU - Kappy NS AD - From the Department of Surgery (N.S.K., S.C., W.M.H., M.P., T.O., P.Z., J.P.C., S.A.B.), Cooper University Hospital, Camden, NJ; and Division of Trauma (J.P.H.), Cooper University Hospital, Camden, NJ. FAU - Chang, Shaohua AU - Chang S FAU - Harris, William M AU - Harris WM FAU - Plastini, Michael AU - Plastini M FAU - Ortiz, Telisha AU - Ortiz T FAU - Zhang, Ping AU - Zhang P FAU - Hazelton, Joshua P AU - Hazelton JP FAU - Carpenter, Jeffrey P AU - Carpenter JP FAU - Brown, Spencer A AU - Brown SA LA - eng PT - Journal Article PL - United States TA - J Trauma Acute Care Surg JT - The journal of trauma and acute care surgery JID - 101570622 RN - 0 (Cytokines) SB - IM MH - Adipocytes/*cytology MH - Animals MH - Brain Injuries, Traumatic/metabolism/pathology/*therapy MH - Cells, Cultured MH - Cytokines/metabolism MH - Disease Models, Animal MH - Humans MH - Male MH - Nerve Regeneration/*physiology MH - Neurons/*pathology MH - Rats MH - Rats, Sprague-Dawley MH - Stem Cell Transplantation/*methods MH - Stem Cells/*cytology MH - Treatment Outcome EDAT- 2017/12/19 06:00 MHDA- 2019/03/05 06:00 CRDT- 2017/12/19 06:00 PHST- 2017/12/19 06:00 [pubmed] PHST- 2019/03/05 06:00 [medline] PHST- 2017/12/19 06:00 [entrez] AID - 10.1097/TA.0000000000001770 [doi] PST - ppublish SO - J Trauma Acute Care Surg. 2018 May;84(5):745-751. doi: 10.1097/TA.0000000000001770.