Encapsulated cell implantation for Parkinson's disease.
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Adrenal Medulla↗
Biomedical subjects
L Christenson
Publications and source records attributed to L Christenson.
A novel approach to neural transplantation in Parkinson's disease: use of polymer-encapsulated cell therapy.
Transplantation of dopaminergic neurons derived from fetal or adrenal tissue into the striatum is a potentially useful treatment for Parkinson's disease (PD). Although initially promising, recent clinical studies using adrenal autografts have demonstrated limited efficacy. The use of human fetal cells, despite promising preliminary results, is complicated by tissue availability and ethical concerns. An attractive alternative is based on encapsulating dopamine-producing cells into polymer capsules prior to transplantation. Polymer capsules can be fabricated to surround the cells with a semi-permeable and immunoprotective barrier. The semi-permeable membrane allows nutrients to enter the capsule, so the encapsulated cells will survive and function, and dopamine and other low molecular weight constituents to diffuse out into the host tissue. Thus, the technique allows use of unmatched human tissue (allografts), or even animal tissue (xenografts) without immunosuppression of the recipient. Cell-loaded polymer capsules can also be retrieved if necessary or desired. The demonstration that striatal implants of encapsulated dopamine-producing cells promote behavioral recovery in rodent and primate models of PD further suggests that cellular encapsulation may be a useful strategy for ameliorating the behavioral consequences of PD.
Adrenal Medulla↗
Mast cells and tissue reaction to intraperitoneally implanted polymer capsules.
The inflammatory reaction to implanted biomaterials often compromises the clinical usefulness of implantable devices. Dexamethasone, an anti-inflammatory agent, acts on macrophages to decrease production of inflammatory mediators, and on mast cells to prevent degranulation. Systemic administration of dexamethasone (dms) in rats decreases the tissue reaction to intraperitoneally implanted vinyl chloride-acrylic copolymer capsules. Local release of even smaller amounts of dms from a polymeric substrate placed inside an acrylic copolymer capsule may control the tissue reaction while avoiding the undesirable side effects of systemic treatment. Such a system also allows investigation of the local effect of soluble molecules on tissue-material interactions without altering the surface properties of the implant or adding the effect of a releasing material. In the present study, we investigated the effect of dms released from ethylene vinyl acetate (EVAc) rods placed in acrylic copolymer capsules and implanted in the peritoneal cavity of rats. In vitro the release of dms from EVAc rods was quasilinear for 5 weeks. When implanted intraperitoneally into rats, polymer capsules containing EVAc/dms rods generated a tissue reaction that was significantly thinner and featured fewer fibroblast and collagen layers than that around capsules containing pure EVAc rods at all time points studied. The tissue reaction layer was also thinner than that previously described in rats treated systemically with dms. The trabeculae of implants with dms-loaded EVAc rods contained significantly more intact mast cells than implants with EVAc alone, suggesting that degranulation of mast cells is involved in the tissue reaction to intraperitoneal polymer implants.
Analysis of Variance↗
Tissue reaction to intraperitoneal polymer implants: species difference and effects of corticoid and doxorubicin.
The peritoneal cavity is a convenient site for implantation of encapsulated hormone-secreting tissue. However, host tissue organization around such implants may affect solute exchange and viability of the encapsulated tissue. The reaction to polyvinyl chloride acrylic copolymer capsules implanted in the peritoneal cavity of rats and mice was therefore studied. Some animals received a slow release dexamethasone pellet, others were pretreated with doxorubicin, in an attempt to minimize the tissue reaction. The tissue reaction was significantly thicker in rats than in mice at both 2 and 6 weeks after implantation. In rats, corticoids decreased significantly the thickness of the reactive layer as compared to control at all time points studied, but doxorubicin had no effect. The tissue reaction in mice was not significantly affected by corticoid treatment. In both species the thickness of the tissue reaction did not increase significantly between 2 and 6 weeks. At 3 days the tissue reaction consisted of an interrupted single layer of macrophages in mice, whereas in rats the reaction consisted of two or three layers of macrophages and polymorphonuclear cells. At both 2 and 6 weeks, several cell layers surrounded the implants: a single layer of macrophages lying along the polymer, a variable number of layers of fibroblasts interspersed with collagen fibrils (fewer in mice than in rats, and fewer in corticoid treated rats than control rats) and an outer monolayer of mesothelial cells. We conclude that the intensity of tissue reaction to polymer implants in the peritoneal cavity is species dependent and can be decreased by the administration of corticoids but not doxorubicin.
Adrenal Cortex Hormones↗
Complications of imaging procedures in six elderly patients.
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Aged↗
Differential expression of T cell differentiation antigens and major histocompatibility antigens on activated T cells during the cell cycle.
In this report we have analyzed cell cycle-related fluctuations of both quantity and density of the T cell differentiation antigens, CD3 (T3), CD4 (T4) and CD8 (T8), as well as the major histocompatibility complex (MHC) antigens on the cell surface of activated T cells. Phytohemagglutinin-activated T cells cultured for 3 days with or without conditioned medium or for 10 days with conditioned medium and mixed lymphocyte culture-derived T cell clones were used for the analysis. Correlated measurements of the surface antigen quantity (immunofluorescence), DNA content (dye Hoechst 33342), and cell size (light scatter), not influenced by synchrony induction methods and cell fixation, were performed by dual-beam flow cytometry. Our results demonstrate that the T cell differentiation antigens, CD3, CD4 and CD8, and class I MHC antigens are increased in density in the G1 phase for all activated T cells tested. In contrast, class II MHC antigens are increased in density in the G2 phase of activated T cells maintained with conditioned medium. Since it is known that the T cell differentiation antigens and class I MHC antigens on activated T cells are necessary for proliferation of T cells, our study suggests that this effect is more significant in the G1 phase. The cell cycle changes in expression of class I and class II MHC antigens, but not of the T cell differentiation antigens, appear to be mediated by soluble factors, probably including interferon-gamma, which could produce a differential increase of class I and class II MHC antigens on G2 phase cells.
Antigens, Differentiation, T-Lymphocyte↗
Investigation of in vivo activated T cells in multiple sclerosis and inflammatory central nervous system diseases.
Monoclonal antibodies have recently been characterized which identify activated T cells at different stages of differentiation. We compared the expression of the late appearing activation antigen defined by monoclonal antibody TS2/7 with the expression of early appearing activation antigens in a group of patients with active multiple sclerosis, encephalitis, non-inflammatory other neurologic diseases, and normal controls. An increase in TS2/7 reactivity of peripheral blood T cells was found in MS patients compared to controls (P less than 0.001), however, there was no increase in the level of early activation antigens. This was in contrast to three patients with viral encephalitis, who had an increase in the early activation antigen 4F2, but minimal, if any, increase in the TS2/7 reactive antigen. This study demonstrates that in vivo, as in vitro, it is possible to identify multiple differentiation stages for activated T cells. Furthermore, the presence of activated T cells in the peripheral blood of multiple sclerosis patients suggests that there is systemic immune activation in MS, and could provide a means to monitor abnormal immunologic activity in MS when these cells are functionally characterized.
Antibodies, Monoclonal↗
Effects of frequent and sustained plateletapheresis on peripheral blood mononuclear cell populations and lymphocyte functions of normal volunteer donors.
Per procedure, plateletapheresis may remove 2 X 10(9) to 3 X 10(9) white cells from the peripheral blood of a normal donor. To investigate the effects of frequent and sustained plateletapheresis, multiple peripheral blood tests were performed on 25 volunteer donors undergoing plateletapheresis an average of 72 times over periods of up to 8 years, and results were compared with 25 age- and sex-matched controls who had not undergone apheresis. In donors, significant decreases were observed in: 1) both absolute number and percentage of T4+ cells; 2) absolute number of both T8+ cells and Leu-7+ cells; 3) T4/T8 ratio; 4) responses to both pokeweed mitogen and alloantigens; and 5) IgG levels. Significant increases were observed in percentages of both B cells and monocytes, and responses to both phytohemagglutinin and Concanavalin A. Plateletapheresis removes a large number of T4 and T8 cells, a moderate number of B cells, and a smaller number of monocytes and Leu-7 cells. The results suggest that during vigorous plateletapheresis the replenishment to peripheral blood per month was less than 1.83 X 10(9) and 0.93 X 10(9) for T4 cells and T8 cells, respectively, greater than 0.27 X 10(9) and 0.62 X 10(9) for B cells and monocytes, respectively, and approximately 0.39 X 10(9) for Leu-7 cells. Although no clinical effect was noted, these data suggest that frequent and sustained non-lymphocyte sparing plateletapheresis is associated with changes in laboratory findings related to the immune system.
Adolescent↗
Encapsulated thymic epithelial cells as a potential treatment for immunodeficiencies.
The epithelial cells of the thymus produce hormones that have been implicated in the maturation of T lymphocytes. Thymic epithelial cells can be encapsulated in a permselective polymer membrane that allows the passage of thymic hormones, but prevents the entry of antibodies, complement, cells, and viruses. A pure culture of thymic epithelial cells, identified as such by transmission electron microscopy and keratin staining, was obtained by low temperature organ culture of fetal mouse thymus. These cells remained intact and produced physiologic amounts of the thymic hormone thymosin alpha-1 after encapsulation in a permselective polymer membrane and in vitro culture for 5 days. An encapsulated implant of thymic epithelial cells may therefore promote reconstitution of an immune system in immunodeficiency diseases without allowing the rejection or destruction of the thymic tissue.
Animals↗