Immunological Rejection (immunological + rejection)

Distribution by Scientific Domains

Selected Abstracts

Commercial considerations in tissue engineering

Jonathan Mansbridge
Abstract Tissue engineering is a field with immense promise. Using the example of an early tissue-engineered skin implant, Dermagraft, factors involved in the successful commercial development of devices of this type are explored. Tissue engineering has to strike a balance between tissue culture, which is a resource-intensive activity, and business considerations that are concerned with minimizing cost and maximizing customer convenience. Bioreactor design takes place in a highly regulated environment, so factors to be incorporated into the concept include not only tissue culture considerations but also matters related to asepsis, scaleup, automation and ease of use by the final customer. Dermagraft is an allogeneic tissue. Stasis preservation, in this case cryopreservation, is essential in allogeneic tissue engineering, allowing sterility testing, inventory control and, in the case of Dermagraft, a cellular stress that may be important for hormesis following implantation. Although the use of allogeneic cells provides advantages in manufacturing under suitable conditions, it raises the spectre of immunological rejection. Such rejection has not been experienced with Dermagraft. Possible reasons for this and the vision of further application of allogeneic tissues are important considerations in future tissue-engineered cellular devices. This review illustrates approaches that indicate some of the criteria that may provide a basis for further developments. Marketing is a further requirement for success, which entails understanding of the mechanism of action of the procedure, and is illustrated for Dermagraft. The success of a tissue-engineered product is dependent on many interacting operations, some discussed here, each of which must be performed simultaneously and well. [source]

Insulin-Producing Cells Derived from Rat Bone Marrow and Their Autologous Transplantation in the Duodenal Wall for Treating Diabetes

Yu-Hua Zhang
Abstract Islet cell transplantation is one of the most promising therapies for diabetes mellitus (DM). However, the limited availability of purified islets for transplantation and the risk of immunological rejection severely limit its use. In vitro transdifferentiation of autologous bone marrow-derived mesenchymal stem cells (BMSCs) into insulin-producing cells (IPCs) could provide an abundant source of cells for this procedure and avoid immunological rejection. Here, we isolated and characterized BMSCs and induced their in vitro differentiation into IPCs. Reverse-transcription polymerase chain reaction analysis revealed that these IPCs could express Ins1, Ins2, glucagon, glucose transporter 2, and pancreatic duodenal homeobox-1. Insulin production by the IPCs was confirmed by immunocytochemistry and Western blot analysis. On this basis, donor rats supplying BMSCs were made diabetic by a single intraperitoneal injection of streptozotocin. The IPCs were then autologously transplanted into the duodenal submucosa of diabetic rats. Grafted cells could be visualized in sections after 2, 4, and 8 weeks by immunohistochemical staining for insulin. Furthermore, in the IPC-implanted group, hyperglycemia was normalized, compared with a persistent increase in glucose levels in the diabetic group and intraperitoneal glucose tolerance test-induced responses were observed in the IPC-implanted group. These results on autologous transplantation of IPCs derived from BMSCs into the duodenal wall could offer a novel potential therapeutical protocol for DM. Anat Rec, 292:728,735, 2009. 2009 Wiley-Liss, Inc. [source]

REVIEW ARTICLE: Immunological Paradigms and the Pathogenesis of Ovine Chlamydial Abortion

Gary Entrican
Citation Entrican G, Wattegedera S, Wheelhouse N, Allan A, Rocchi M. Immunological paradigms and the pathogenesis of ovine chlamydial abortion. Am J Reprod Immunol 2010 Successful mammalian pregnancy involves complex immunological interactions between the mother and foetus that are not yet fully understood. A number of immunological paradigms have been established to explain the failure of the maternal immune system to reject the semi-allogeneic foetus, mainly based on studies in mice and humans. However, as placental structure, gestation periods and number of concepti per pregnancy can vary greatly between mammals, it is not always clear how applicable these immunological paradigms are to reproduction in other species. Here, we discuss the predictions of three important immunological paradigms in relation to the pathogenesis of ovine enzootic abortion (OEA), a common cause of infectious abortion in sheep and other ruminants. OEA is caused by the intracellular Gram-negative bacterium Chlamydophila abortus that exhibits a tropism for placental trophoblast. The paradigms of particular relevance to the pathogenesis of OEA are as follows: (i) intracellular bacterial infections are controlled by TH1-type CD4+ve T cells; (ii) indoleamine 2,3-dioxygenase is expressed in the placenta to prevent immunological rejection of the semi-allogeneic foetus; and (iii) pregnancy is a maternal TH2-type phenomenon. We discuss the relevance and validity of these paradigms for chlamydial abortion and reproductive immunology in sheep. [source]

Immunoregulatory Activity, Biochemistry, and Phylogeny of Ovine Uterine Serpin

PROBLEM: During pregnancy, the endometrium of the ewe secretes a progesterone-induced member of the serpin superfamily of serine proteinase inhibitors called ovine uterine serpin (OvUS) that has immunosuppressive properties. METHOD: Review of the literature. RESULTS AND CONCLUSIONS: OvUS inhibits a wide variety of immune responses, including mixed lymphocyte reaction, mitogen-stimulated lymphocyte proliferation, and T cell-dependent antibody production. Recent data have suggested that OvUS functions by inhibiting protein kinase C and interleukin-2-mediated events. OvUS and similar genes present in cattle and pigs diverged from other serpins prior to the divergence of artiodactyls. Since this time, the serpins have apparently undergone adaptive evolution that has led to a conformational state and biological functions distinct from prototypical serpins. Thus, it is likely that these proteins have an important role in the reproductive biology of Artiodactyla. Several lines of evidence suggest that, in sheep, OvUS functions to mediate the immunosuppressive effects of progesterone and prevent immunological rejection of the fetal allograft. [source]