Effects of histocompatibility and host immune responses on the tumorigenicity of pluripotent stem cells

Pluripotent stem cells hold great promises for regenerative medicine. They might become useful as a universal source for a battery of new cell replacement therapies. Among the major concerns for the clinical application of stem cell-derived grafts are the risks of immune rejection and tumor formation. Pluripotency and tumorigenicity are closely linked features of pluripotent stem cells. However, the capacity to form teratomas or other tumors is not sufficiently described by inherited features of a stem cell line or a stem cell-derived graft. The tumorigenicity always depends on the inability of the recipient to reject the tumorigenic cells. This review summarizes recent data on the tumorigenicity of pluripotent stem cells in immunodeficient, syngeneic, allogeneic, and xenogeneic hosts. The effects of immunosuppressive treatment and cell differentiation are discussed. Different immune effector mechanisms appear to be involved in the rejection of undifferentiated and differentiated cell populations. Elements of the innate immune system, such as natural killer cells and the complement system, which are active also in syngeneic recipients, appear to preferentially reject undifferentiated cells. This effect could reduce the risk of tumor formation in immunocompetent recipients. Cell differentiation apparently increases susceptibility to rejection by the adaptive immune system in allogeneic hosts. The current data suggest that the immune system of the recipient has a major impact on the outcome of pluripotent stem cell transplantation, whether it is rejection, engraftment, or tumor development. This has to be considered when the results of experimental transplantation models are interpreted and even more when translation into clinics is planned

Energetic instability of passive states in thermodynamics

Passivity is a fundamental concept in thermodynamics that demands a quantum system’s energy cannot be lowered by any reversible, unitary process acting on the system. In the limit of many such systems, passivity leads in turn to the concept of complete passivity, thermal states and the emergence of a thermodynamic temperature. Here we only consider a single system and show that every passive state except the thermal state is unstable under a weaker form of reversibility. Indeed, we show that given a single copy of any athermal quantum state, an optimal amount of energy can be extracted from it when we utilise a machine that operates in a reversible cycle. This means that for individual systems, the only form of passivity that is stable under general reversible processes is complete passivity, and thus provides a physically motivated identification of thermal states when we are not operating in the thermodynamic limit

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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How to cross immunogenetic hurdles to human embryonic stem cell transplantation

Implantation of human embryonic stem cells (hES), derived progenitors or mature cells derived from hES has great therapeutic potential for many diseases. If hES would come from genetically unrelated individuals, it would be probably rejected by the immune system of the recipient. Blood groups, MHC and minor antigens are the immunogenetic hurdles that have to be crossed for successful transplantation. Autologous transplantation with adult stem cells would be the best approach but several elements argue against this option. Classical immunosuppression, depleting antibody, induction of tolerance and stem cell banking are alternative methods that could be proposed to limit the risk of rejection