Mobilization of Mesenchymal Stem Cells During Liver Transplantation

Mesenchymal stem cells (MSCs) are a known immune modulator with significant immunosuppressive effects. MSCs have emerged as a promising frontier in human clinical trials. MSCs have been shown to be non-immunogenic making them capable of transplantation across allogeneic barrier. These qualities make MSCs an ideal candidate to study if they are involved in reducing the rejection of the graft, in this case, liver transplant. If so, the information would be highly significant as it would lead to significant reduction in use of immunosuppressants with the replacement of MSCs. This will serve dual purposes: reduced clinical problems associated with pharmacological immunosuppression (discussed in the next paragraph); additional help in the protection of the transplanted liver by the MSCs.

The use of immunosuppressants in particular is vital in organ transplantation including liver transplant patients. However, their use is accompanied by numerous drawbacks such as reactivation of viral hepatitis, opportunistic infections and other complications. If MSCs can be used to decrease the use of immunosuppressive agents in liver transplant patients it can lead to a significant decrease in morbidity and mortality as a consequence of liver transplantation.

Hepatic macrophages, ie Kupffer cells, have a known function of recruiting monocytes into the liver. They have been shown to have a proinflammatory effect by attracting monocytes into the liver. They also interact with hepatic stellate cells (HSCs) which have pro-fibrogenic functions. However, they have been shown to have anti-inflammatory effects as well, implicating a role in fibrosis regression. Hepatic macrophages are an interesting new target for therapeutic intervention and the effect of steroids on kupffer cells as well as their interaction with MSCs have not been fully explored.

Patient will be attached to standard American Society of Anesthesiologists (ASA) monitors including pulse oximetry, electrocardiogram, noninvasive blood pressure monitoring temperature and capnometry. Patients will be placed under general anesthesia with endotracheal intubation and controlled ventilation. As is customary for all liver surgeries, an arterial line will be inserted for blood pressure monitoring and for repeat blood samples. If indicated, a pulmonary artery catheter will be inserted.

Anesthesia will be maintained using a volatile agent. Paralysis will be provided using a non-depolarizing neuromuscular blocking agent of the anesthesiologist's choice.