| 1. |
- Blixt Wojciechowski, Anita, et al.
(författare)
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Long-term survival and glial differentiation of the brain-derived precursor cell line RN33B after subretinal transplantation to adult normal rats
- 2002
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 20:2, s. 163-173
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Tidskriftsartikel (refereegranskat)abstract
- The potential use of in vitro-expanded precursor cells or cell lines in repair includes transplantation of such cells for cell replacement purposes and the activation of host cells to provide "self-repair." Recently, we have reported that cells from the brain-derived cell line RN33B (derived from the embryonic rat medullary raphe and immortalized through retroviral transduction of the temperature-sensitive mutant of the simian virus 40 ([SV40] large T-antigen) survive for at least 4 weeks, integrate, and differentiate after subretinal grafting to normal adult rats. Here, we demonstrate that grafts of these cells survive for at least 4 months after subretinal transplantation to adult, normal immunosuppressed rats. Implanted cells integrate into the retinal pigment epithelium and the inner retinal layers, and the anterior part of the optic nerve. In addition, the RN33B cells migrate within the retina, occupying the whole retina from one eccentricity to the other. A large fraction of the grafted cells differentiate into glial cells, as shown by double labeling of the reporter genes LacZ or green fluorescent protein, and several glial markers, including oligodendrocytes. However, the cells did not differentiate into retinal neurons, judging from their lack of expression of retinal neuronal phenotypic markers. A significant number of the implanted cells in the host retina were in a proliferative stage, judging from proliferative cell nuclear antigen and SV40 large T-antigen immunohistochemistry. To conclude, the cells survived, integrated, and migrated over long distances within the host. Therefore, our results may be advantageous for future design of therapeutic strategies, since such cells may have the potential of being a source of, for example, growth factor delivery in experimental models of retinal degeneration.
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| 2. |
- Blixt Wojciechowski, Anita, et al.
(författare)
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Survival and long distance migration of brain-derived precursor cells transplanted to adult rat retina
- 2004
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Ingår i: Stem Cells. - : AlphaMed Press. - 1549-4918 .- 1066-5099. ; 22:1, s. 27-38
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Tidskriftsartikel (refereegranskat)abstract
- Neural precursor cells transplanted to adult retina can integrate into the host. This is especially true when the neural precursor rat cell line RN33B is used. This cell line carries the reporter genes LacZ and green fluorescent protein (GFP). In grafted rat eyes, RN33B cells are localized from one eccentricity to the other of the host retina. In the present study, whole-mounted retinas were analyzed to obtain a more appropriate evaluation of the amount of transgene-expressing cells and the migratory capacity of these cells 3 and 8 weeks post-transplantation. Quantification was made of the number of beta-galactosidase- and GFP-expressing cells with a semiautomatized stereological cell counting system. With the same system, delineation of the distribution area of the grafted cells was also performed. At 3 weeks, 68% of the grafted eyes contained marker-expressing cells, whereas at 8 weeks only 35% of the eyes contained such cells. Counting of marker-expressing cells demonstrated a lower number of transgene-expressing cells at 3 weeks compared with 8 weeks post-transplantation. The distribution pattern of marker gene-expressing cells revealed cells occupying up to 21% at 3 weeks and up to 68% at 8 weeks of the entire host retina post-grafting. The precursor cells survived well in the adult retina although the most striking feature of the RN33B cell line was its extraordinary migratory capacity. This capability could be useful if precursor cells are used to deliver necessary genes or gene products that need to be distributed over a large diseased area.
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| 3. |
- Heldin, Carl-Henrik
(författare)
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Signal transduction : multiple pathways, multiple options for therapy
- 2001
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 19:4, s. 295-303
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Tidskriftsartikel (refereegranskat)abstract
- Many aspects of cell behavior, such as growth, motility, differentiation, and apoptosis, are regulated by signals cells receive from their environment. Such signals are important, e.g., during embryonal development, wound healing, hematopoiesis, and in the regulation of the immune response, and may come from interactions with other cells or components of the extracellular matrix, or from binding of soluble signaling molecules to specific receptors at the cell membrane. Hereby different signaling pathways are initiated inside the cell. Perturbations of such signaling pathways are seen in several types of diseases, e.g., cancer, inflammatory conditions, and atherosclerosis. Thus, antagonists of several signaling pathways have potential clinical utility. Several such compounds are currently used or are in clinical trials; others are currently being analyzed in animal models.
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