Search

The following position paper summarizes the recommendations for early clinical trials and ongoing basic research in the field of mesenchymal stem cell-induced solid organ graft acceptance--agreed upon on the first meeting of the Mesenchymal Stem Cells In Solid Organ Transplantation (MISOT) study group in late 2008.

It has recently been recognized that mesenchymal stem cells (MSCs) isolated from adult bone marrow are able to modify the alloimmune response in vitro and in vivo. MSCs can be expanded into large quantities in culture, thereby facilitating potential future applications in solid organ transplantation. To develop novel MSC-based antirejection treatments, the mechanism behind the immunomodulatory ability of MSCs has to be elucidated further. At present, a variety of possible in vitro effects of MSCs on immune system effector cells have been reported, but little is known about their in vivo properties. Here, we discuss recent findings regarding the influence of MSCs on different effector cell populations in vitro and summarize the available data describing their in vivo properties.

The induction of tolerance towards allogeneic solid organ grafts is one of the major goals in transplantation medicine. Mesenchymal stem cells (MSC) inhibit the proliferation of T cells in vitro, and thus are promising candidate cells to promote acceptance of transplanted organs in vivo. Such novel approaches of tolerance induction are needed since, to date, graft acceptance can only be maintained through lifelong treatment with unspecific immunosuppressants that are associated with toxic injury, opportunistic infections and malignancies. In our current work, we demonstrate that donor-derived MSC induce long-term allograft acceptance in a rat heart transplantation model, when concurrently applied with a short course of low-dose mycophenolate. The tolerogenic effect of MSC was mediated by the expression of indoleamine 2,3-dioxygenase (IDO), outlined by the fact that blocking of IDO with 1-methyl tryptophan (1-MT) abrogated graft acceptance. In this respect, MSC-mediated tolerance is different from donor leukocyte-mediated tolerance. The application of donor leucocytes also induced graft acceptance in our model, but not through IDO, since blocking of IDO did not result in graft rejection. In summary, we demonstrate that MSC constitute a promising tool for the induction of non-responsiveness in solid organ transplantation that warrants further investigation in clinical studies.

Natural killer cells (NK cells) play a key role in cancer immunosurveillance. However, their activity is highly dependent upon their maturation stage, which in turn relates to organ distribution. Here, we discuss the role of intrinsic master transcription factors and extrinsic IL-15 signaling on NK cell-mediated immune protection against murine pulmonary metastasis.

Static and dynamic games are important tools for the analysis of strategic interactions among economic agents and have found many applications in economics. In many games equilibria can be described as solutions of polynomial equations. In this paper we describe state-of-the-art techniques for finding all solutions of polynomial systems of equations and illustrate these techniques by computing all equilibria of both static and dynamic games with continuous strategies. We compute the equilibrium manifold for a Bertrand pricing game in which the number of equilibria changes with the market size. Moreover, we apply these techniques to two stochastic dynamic games of industry competition and check for equilibrium uniqueness. Our examples show that the all-solution methods can be applied to a wide variety of policy-relevant models.

Acute kidney injury (AKI) in surgical critically ill patients is an independent risk factor for early mortality. Two novel urine biomarkers, insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), may help to detect clinically silent episodes of AKI in the golden hours prior to irreversible damage of the kidney. We evaluated the early predictive value of these biomarkers for AKI, moderate and severe AKI, early requirement of renal replacement therapy (RRT), and ICU mortality, with a cutoff value of IGFBP7/TIMP-2 >0.3.