• Kiran K Nandra, Kunihiko Takahashi, Massimo Collino, Elisa Benetti, W S Fred Wong, Fera Y Goh, Ken Suzuki, Nimesh S A Patel, and Chris Thiemermann.
• The William Harvey Research Institute, Queen Mary University of London, Barts and the London School of Medicine and Dentistry, London, UK.
• Shock. 2012 Jun 1;37(6):592-8.

AbstractRecent 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.

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