title: Acute treatment with bone marrow-derived mononuclear cells attenuates the organ injury/dysfunction induced by hemorrhagic shock in the rat.
abstract: Recent evidence suggests that cell therapy such as the injection of bone marrow-derived mononuclear cells (BMMNCs) can exert protective effects in various conditions associated with ischemia-reperfusion injury. Here, we investigate the effects of BMMNCs on the organ injury/dysfunction induced by hemorrhagic shock (HS). Thirty-seven anesthetized male Wistar rats were subjected to hemorrhage by reducing mean arterial pressure to 35 ± 5 mmHg for 90 min, followed by resuscitation with 20 mL/kg Ringer's lactate administered over 10 min and 50% of the shed blood over 50 min. Rats were killed 4 h after the onset of resuscitation. Bone marrow-derived mononuclear cells were freshly isolated from rat tibias and femurs using Percoll density gradient centrifugation, and BMMNCs (1 × 10 cells per rat in 1 mL/kg phosphate-buffered saline, i.v.) were administered on resuscitation. Hemorrhagic shock resulted in significant organ injury/dysfunction (renal, hepatic, neuromuscular) and inflammation (hepatic, lung). In rats subjected to HS, administration of BMMNCs significantly attenuated (i) organ injury/dysfunction (renal, hepatic, neuromuscular) and inflammation (hepatic, lung), (ii) increased the phosphorylation of Akt and glycogen synthase kinase-3β, (iii) attenuated the activation of nuclear factor-κB, (iv) attenuated the increase in extracellular signal-regulated kinase 1/2 phosphorylation, and (v) attenuated the increase in expression of intercellular adhesion molecule-1. Our findings suggest that administration of BMMNCs protects against the induction of early organ injury/dysfunction caused by severe HS by a mechanism that may involve activation of Akt and the inhibition of glycogen synthase kinase-3β and nuclear factor-κB.
authors.affiliation: The William Harvey Research Institute, Queen Mary University of London, Barts and the London School of Medicine and Dentistry, London, UK.
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Nandra
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Massimo
authors.initials: M
authors.lastname: Collino
authors.forename: Elisa
authors.initials: E
authors.lastname: Benetti
authors.forename: W S Fred
authors.initials: WS
authors.lastname: Wong
authors.forename: Fera Y
authors.initials: FY
authors.lastname: Goh
authors.forename: Ken
authors.initials: K
authors.lastname: Suzuki
authors.forename: Nimesh S A
authors.initials: NS
authors.lastname: Patel
authors.forename: Chris
authors.initials: C
authors.lastname: Thiemermann
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D017690:Cell Transplantation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D009000:Monocytes / Q000637:transplantation*; D051058:Oncogene Protein v-akt; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012771:Shock, Hemorrhagic / Q000503:physiopathology* / Q000628:therapy*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: C498145:Rela protein, rat; D051996:Transcription Factor RelA; D009195:Peroxidase; D051058:Oncogene Protein v-akt; D038362:Glycogen Synthase Kinase 3