In vitro evaluation of new possible cell engraftment enhancers for cell transplantation.

Orthotopic liver transplantation (OLT) is the best treatment to restore liver function in liver failure. The low availability of organs has focused interest on the use of cell transplantation to restore liver function. However, this technique is limited because cells can not bind to liver parenchyma and die soon after perfusion. Pretransplant treatment with engraftment enhancers (EE) to increase vascular permeability may increase cell attachment. Using an endothelial cell culture to measure the loss of intercellular endothelial adhesion as a screening test, we evaluated the capacity of 15 monoclonal antibodies against adhesion molecules expressed on endothelial cells to act as EE showing that 3 antibodies (anti-CD54, efalizumab, and abciximab) act as EE by producing disruptions in the cell layer.

Peripheral blood regulatory T cells in long-term kidney transplant recipients.

Regulatory T lymphocytes (Treg) suppress activation of the immune system and prevent pathological autoreactivity, giving them a relevant role in transplantation. In this study, we compared the proportion of Treg in a group of kidney transplant recipients with those in a control group. We used flow cytometry and labeling with monoclonal CD4, CD25, and FoxP3 antibodies to analyze the percentage of Treg lymphocytes in peripheral blood in a group of 68 patients at more than 12 years since transplantation and in 16 untransplanted healthy controls. In addition to the laboratory determinations, we analyzed the effect of some clinical parameters on the percentage of Treg in the transplanted group with a previous history of hepatitis C virus infection and undergoing immunosuppressive treatment. The percentage of Treg levels observed in the transplanted group was significantly lower than that in the control group (1.53% vs 2.89% CD4+ T cells; P = .0022). The percentage of Treg cells was significantly lower among patients treated with mycophenolate mofetil (1.12%) than other drug combinations. We also compared the percentage of Treg between transplant recipients treated with immunosuppressive monotherapy and those treated with combined immunosuppression, observing a higher percentage among patients with monotherapy.

An in vitro model of cell transplantation for evaluation of cell engraftment enhancers.

The limited availability of organs for liver transplantation has focused interest on the use of cell transplants to restore hepatic function. Advances have been made in rodent models, but efficacy is limited in humans due to low engraftment efficiency. In rodents, pretransplantation treatment of the liver with engraftment enhancers (EE) shows that repopulation is feasible, although the toxicity of the substances impedes their application in humans. Evaluation of low-toxicity engraftment enhancers for human use requires testing in animal models, a time-consuming, expensive process that also raises ethical issues. To reduce animal use in the preliminary evaluation of a new EE, we designed an easily quantitated in vitro method that mimics an intraportal cell transplant. It is based on EE-mediated disruption of intercellular adhesion in confluent endothelial cell cultures.