| 1. |
- Rafael, E, et al.
(author)
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In vivo evaluation of glucose permeability of an immunoisolation device intended for islet transplantation: a novel application of the microdialysis technique
- 1999
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In: Cell transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 8:3, s. 317-326
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Journal article (peer-reviewed)abstract
- Immunoisolation devices consist of semipermeable membranes chosen to protect the islets from the immune system but still allow sufficient passage of nutrients, oxygen, and the therapeutic products, insulin. The exchange between the device and the microcirculation will influence the survival of the graft as well as the metabolic efficacy of the islet implant. Glucose is the important trigger factor for insulin secretion. In this study, we evaluate the in vivo glucose permeability of the Theracyte™ immunoisolation device at various times after implantation. Empty devices were implanted SC in rats. The glucose kinetics in the device was compared to that in the SC tissue during IV glucose tolerance tests (IVGTTs), using the microdialysis technique. In rats studied on day 1, or 1, 2, and 4 weeks after implantation, the peak glucose levels (Cmax) were significantly lower, the times-to-peak (TTP) were significantly longer, and the areas under the curve during the first 40 min (AUC0–40) were significantly smaller in the device than in the SC fat. However, at 3 months all parameters improved and Cmax, TTP, and AUC0–40 in the device did not differ significantly from those measured in the SC fat. Thus, during the first 4 weeks the device constitutes a significant diffusion barrier, but at 3 months the exchange between the lumen of devices and the blood stream improves. Our data indicate that implantation of the device several months before transplantation of the cellular graft would improve the exchange across the membrane during the early posttransplant period. This should have positive effects on graft survival and function. We also suggest that microdialysis is a useful tool for evaluating the in vivo performance of macroencapsulation devices.
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| 2. |
- Stromberg, I, et al.
(author)
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The age of striatum determines the pattern and extent of dopaminergic innervation: a nigrostriatal double graft study
- 1997
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In: Cell transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 6:3, s. 287-296
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Journal article (peer-reviewed)abstract
- In animal models of Parkinson's disease, transplanted fetal mesencephalic dopaminergic neurons can innervate the dopamine-depleted host brain, but it is unclear why large portions of the host striatum are left uninnervated. During normal development, the dopaminergic innervation first occurs in the form of a dense patchy pattern in the striatum, followed by a widespread nerve fiber network. Using intraocular double grafts we have investigated dopaminergic growth patterns initiated when ventral mesencephalic grafts innervate striatal targets. The fetal lateral ganglionic eminence was implanted into the anterior eye chamber. After maturation in oculo, fetal ventral mesencephalon was implanted and placed in contact with the first graft. In other animals the two pieces of tissue were implanted simultaneously. Tyrosine hydroxylase (TH) immunohistochemistry revealed a pattern of dense TH-positive patches throughout the total volume of the striatal grafts in simultaneously transplanted cografts, while a widespread, less dense, pattern was found when mature striatal transplants were innervated by fetal dopaminergic grafts. To investigate which type or types of growth patterns that developed after grafting to striatum in situ of an adult host, fetal ventral mesencephalic tissue was implanted into the lateral ventricle adjacent to the dopamine-lesioned striatum. After maturation of the mesencephalic graft, the fetal lateral ganglionic eminence was implanted into the reinnervated part of the host striatum. TH immunohistochemistry revealed a few nerve fibers within the striatal graft and the growth pattern was of the widespread type. In conclusion, grafted dopaminergic neurons preferably innervate mature striatum with a widespread sparse nerve fiber network, while the innervation of the immature striatum occurs in the form of dense patches. Furthermore, when the patchy pattern is formed, the total volume of the striatal target is innervated while growth of the widespread type terminates prior to reaching distal striatal parts. Thus, the growth pattern seems essential to the final volume that is innervated. Once the widespread growth pattern is initiated, the presence of immature striatum does not change the dopaminergic growth pattern.
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| 3. |
- Sumitran-Holgersson, S, et al.
(author)
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Porcine embryonic brain cell cytotoxicity mediated by human natural killer cells
- 1999
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In: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 8:6, s. 10-601
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Journal article (peer-reviewed)abstract
- Intracerebral transplantation of porcine embryonic dopamine-producing neurons has been suggested as a method to treat patients with Parkinson's disease. Even though the brain is an immunologically privileged site, neuronal xenografts are usually rejected within a few weeks. T cells are important for this process, but the exact cellular events leading to rejection are poorly characterized. Brain cells from ventral mesencephalon of 26-27-day-old pig embryos were used as target cells in flow cytometry-assessed cytotoxicity assays using non- and IL-2-activated CD3- CD16+ CD56+ human natural killer (NK) cells as effector cells. The ability of human NK cells to kill pig embryonic brain cells by antibody-dependent cellular cytotoxicity (ADCC) in the presence of nondepleted and anti-Gal alpha1,3Gal antibody-depleted human blood group AB serum (AB serum) was evaluated using the same assay. Both nondepleted and anti-Gal alpha1,3Gal antibody-depleted AB serum could mediate ADCC of pig embryonic VM cells when human NK cells were used as effector cells. Nonactivated NK cells did not show any direct cytotoxic effect on freshly isolated VM cells, whereas IL-2-activated NK cells killed approximately 50% of the VM cells at an effector-to-target ratio of 50:1 in a 4-h cytotoxicity assay. Activation of VM cells by TNF-alpha did not change their sensitivity to human NK cell cytotoxicity. Human NK cells may thus contribute to a cellular rejection of pig neuronal xenografts by ADCC, or following IL-2 activation, by a direct cytotoxic effect.
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