| 1. |
- Abbot, Stewart, et al.
(author)
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Report of the international conference on manufacturing and testing of pluripotent stem cells
- 2018
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In: Biologicals. - : Elsevier BV. - 1045-1056. ; 56, s. 67-83
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Journal article (other academic/artistic)abstract
- Sessions included an overview of past cell therapy (CT) conferences sponsored by the International Alliance for Biological Standardization (IABS). The sessions highlighted challenges in the field of human pluripotent stem cells (hPSCs) and also addressed specific points on manufacturing, bioanalytics and comparability, tumorigenicity testing, storage, and shipping. Panel discussions complemented the presentations. The conference concluded that a range of new standardization groups is emerging that could help the field, but ways must be found to ensure that these efforts are coordinated. In addition, there are opportunities for regulatory convergence starting with a gap analysis of existing guidelines to determine what might be missing and what issues might be creating divergence. More specific global regulatory guidance, preferably from WHO, would be welcome. IABS and the California Institute for Regenerative Medicine (CIRM) will explore with stakeholders the development of a practical and innovative road map to support early CT product (CTP) developers.
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| 2. |
- Maruyama, Toshi, et al.
(author)
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Hypothermia-induced tyrosine phosphorylation of SIRPα in the brain
- 2012
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In: Journal of Neurochemistry. - : John Wiley & Sons. - 0022-3042 .- 1471-4159. ; 121:6, s. 891-902
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Journal article (peer-reviewed)abstract
- Signal regulatory protein α (SIRPα) is a neuronal membrane protein that undergoes tyrosine phosphorylation in the brain of mice in response to forced swim (FS) stress in cold water, and this response is implicated in regulation of depression-like behavior in the FS test. We now show that subjection of mice to the FS in warm (37°C) water does not induce the tyrosine phosphorylation of SIRPα in the brain. The rectal temperature (T(rec) ) of mice was reduced to 27° to 30°C by performance of the FS for 10 min in cold water, whereas it was not affected by the same treatment in warm water. The level of tyrosine phosphorylation of SIRPα in the brain was increased by administration of ethanol or picrotoxin, starvation, or cooling after anesthesia, all of which also induced hypothermia. Furthermore, the tyrosine phosphorylation of SIRPα in cultured hippocampal neurons was induced by lowering the temperature of the culture medium. CD47, a ligand of SIRPα, as well as Src family kinases or SH2 domain-containing protein phosphatase 2 (Shp2), might be important for the basal and the hypothermia-induced tyrosine phosphorylation of SIRPα. Hypothermia is therefore likely an important determinant of both the behavioral immobility and tyrosine phosphorylation of SIRPα observed in the FS test.
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| 3. |
- Saito, Yasuyuki, et al.
(author)
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Regulation by SIRPα of dendritic cell homeostasis in lymphoid tissues
- 2010
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 116:18, s. 3517-3525
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Journal article (peer-reviewed)abstract
- The molecular basis for regulation of dendritic cell (DC) development and homeostasis remains unclear. Signal regulatory protein α (SIRPα), an immunoglobulin superfamily protein that is predominantly expressed in DCs, mediates cell-cell signaling by interacting with CD47, another immunoglobulin superfamily protein. We now show that the number of CD11c(high) DCs (conventional DCs, or cDCs), in particular, that of CD8-CD4+ (CD4+) cDCs, is selectively reduced in secondary lymphoid tissues of mice expressing a mutant form of SIRPα that lacks the cytoplasmic region. We also found that SIRPα is required intrinsically within cDCs or DC precursors for the homeostasis of splenic CD4+ cDCs. Differentiation of bone marrow cells from SIRPα mutant mice into DCs induced by either macrophage-granulocyte colony-stimulating factor or Flt3 ligand in vitro was not impaired. Although the accumulation of the immediate precursors of cDCs in the spleen was also not impaired, the half-life of newly generated splenic CD4+ cDCs was markedly reduced in SIRPα mutant mice. Both hematopoietic and nonhematopoietic CD47 was found to be required for the homeostasis of CD4+ cDCs and CD8-CD4- (double negative) cDCs in the spleen. SIRPα as well as its ligand, CD47, are thus important for the homeostasis of CD4+ cDCs or double negative cDCs in lymphoid tissues.
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| 4. |
- Sato-Hashimoto, Miho, et al.
(author)
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Microglial SIRP alpha regulates the emergence of CD11c(+) microglia and demyelination damage in white matter
- 2019
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In: eLIFE. - : eLIFE Sciences Publications. - 2050-084X. ; 8
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Journal article (peer-reviewed)abstract
- A characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c(+) microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein alpha (SIRP alpha), a membrane protein, induced the emergence of CD11c(+) microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRP alpha, and microglia-specific SIRP alpha-knockout mice exhibited the same phenotype, suggesting that an interaction between microglial SIRP alpha and CD47 on neighbouring cells suppressed the emergence of CD11c(+) microglia. A lack of SIRP alpha did not cause detectable damage to the white matter, but resulted in the increased expression of genes whose expression is characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRP alpha. Thus, microglial SIRP alpha suppresses the induction of CD11c(+) microglia that have the potential to accelerate the repair of damaged white matter.
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| 5. |
- Sato-Hashimoto, Miho, et al.
(author)
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Signal regulatory protein α regulates the homeostasis of T lymphocytes in the spleen.
- 2011
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In: Journal of Immunology. - : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 187:1, s. 291-297
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Journal article (peer-reviewed)abstract
- The molecular basis for formation of lymphoid follicle and its homeostasis in the secondary lymphoid organs remains unclear. Signal regulatory protein α (SIRPα), an Ig superfamily protein that is predominantly expressed in dendritic cells or macrophages, mediates cell-cell signaling by interacting with CD47, another Ig superfamily protein. In this study, we show that the size of the T cell zone as well as the number of CD4(+) T cells were markedly reduced in the spleen of mice bearing a mutant (MT) SIRPα that lacks the cytoplasmic region compared with those of wild-type mice. In addition, the expression of CCL19 and CCL21, as well as of IL-7, which are thought to be important for development or homeostasis of the T cell zone, was markedly decreased in the spleen of SIRPα MT mice. By the use of bone marrow chimera, we found that hematopoietic SIRPα is important for development of the T cell zone as well as the expression of CCL19 and CCL21 in the spleen. The expression of lymphotoxin and its receptor, lymphotoxin β receptor, as well as the in vivo response to lymphotoxin β receptor stimulation were also decreased in the spleen of SIRPα MT mice. CD47-deficient mice also manifested phenotypes similar to SIRPα MT mice. These data suggest that SIRPα as well as its ligand CD47 are thus essential for steady-state homeostasis of T cells in the spleen.
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