Transplantation of dendritic cells promotes functional recovery from spinal cord injury in common marmoset

Yaguchi, Masatsugu; Tabuse, Masanao; Ohta, Shigeki; Ohkusu-Tsukada, Kozo; Takeuchi, T.; Yamane, Junichi; Katoh, Hiroyuki; Nakamura, Masaya; Matsuzaki, Yuji; Yamada, Masayuki; Itoh, Toshio; Nomura, Tatsuji; Toyama, Yoshiaki; Toda, Masahiro

doi:10.1016/j.neures.2009.08.016

Cited by 23 publications

(16 citation statements)

References 47 publications

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“…To examine the effects of DCs on SCI, we characterized DCs derived from bone marrows of common marmosets (Ohta et al, 2008), and observed functional recovery from SCI by DC transplantation (Yaguchi et al, 2009) in our established SCI model (Iwanami et al, 2005), suggesting that DCs may be used for SCI therapy. In the mouse SCI model, cDCs have been shown to induce de novo neurogenesis in vivo and to increase NSPC proliferation in vitro and in vivo, although details of the mechanism underlying this induction remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Macrophage migration inhibitory factor (MIF) promotes cell survival and proliferation of neural stem/progenitor cells

Ohta

Misawa

Fukaya

et al. 2012

Journal of Cell Science

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117

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SummaryIn a previous study, we showed that murine dendritic cells (DCs) can increase the number of neural stem/progenitor cells (NSPCs) in vitro and in vivo. In the present study, we identified macrophage migration inhibitory factor (MIF) as a novel factor that can support the proliferation and/or survival of NSPCs in vitro. MIF is secreted by DCs and NSPCs, and its function in the normal brain remains largely unknown. It was previously shown that in macrophages, MIF binds to a CD74-CD44 complex. In the present study, we observed the expression of MIF receptors in mouse ganglionic-eminence-derived neurospheres using flow cytometry in vitro. We also found CD74 expression in the ganglionic eminence of E14 mouse brains, suggesting that MIF plays a physiological role in vivo. MIF increased the number of primary and secondary neurospheres. By contrast, retrovirally expressed MIF shRNA and MIF inhibitor (ISO-1) suppressed primary and secondary neurosphere formation, as well as cell proliferation. In the neurospheres, MIF knockdown by shRNA increased caspase 3/7 activity, and MIF increased the phosphorylation of Akt, Erk, AMPK and Stat3 (Ser727), as well as expression of Hes3 and Egfr, the products of which are known to support cell survival, proliferation and/or maintenance of NSPCs. MIF also acted as a chemoattractant for NSPCs. These results show that MIF can induce NSPC proliferation and maintenance by multiple signaling pathways acting synergistically, and it may be a potential therapeutic factor, capable of activating NSPC, for the treatment of degenerative brain disorders.

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Section: Introductionmentioning

confidence: 99%

Macrophage migration inhibitory factor (MIF) promotes cell survival and proliferation of neural stem/progenitor cells

Ohta

Misawa

Fukaya

et al. 2012

Journal of Cell Science

Self Cite

117

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“…The common marmoset ( Callithrix jacchus ) is a New World monkey and is considered potentially useful as an experimental animal model in research fields such as drug toxicology [1], [2], neuroscience [3], [4], autoimmune diseases [5], [6] and infectious diseases [7], [8], because of its size, availability and high genetic similarity with humans [9], [10]. Compared with mice, common marmosets are more useful as an in vivo model to study immune function [11].…”

Section: Introductionmentioning

confidence: 99%

Immune-Related Gene Expression Profile in Laboratory Common Marmosets Assessed by an Accurate Quantitative Real-Time PCR Using Selected Reference Genes

et al. 2013

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The common marmoset (Callithrix jacchus) is considered a novel experimental animal model of non-human primates. However, due to antibody unavailability, immunological and pathological studies have not been adequately conducted in various disease models of common marmoset. Quantitative real-time PCR (qPCR) is a powerful tool to examine gene expression levels. Recent reports have shown that selection of internal reference housekeeping genes are required for accurate normalization of gene expression. To develop a reliable qPCR method in common marmoset, we used geNorm applets to evaluate the expression stability of eight candidate reference genes (GAPDH, ACTB, rRNA, B2M, UBC, HPRT, SDHA and TBP) in various tissues from laboratory common marmosets. geNorm analysis showed that GAPDH, ACTB, SDHA and TBP were generally ranked high in stability followed by UBC. In contrast, HPRT, rRNA and B2M exhibited lower expression stability than other genes in most tissues analyzed. Furthermore, by using the improved qPCR with selected reference genes, we analyzed the expression levels of CD antigens (CD3ε, CD4, CD8α and CD20) and cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12β, IL-13, IFN-γ and TNF-α) in peripheral blood leukocytes and compared them between common marmosets and humans. The expression levels of CD4 and IL-4 were lower in common marmosets than in humans whereas those of IL-10, IL-12β and IFN-γ were higher in the common marmoset. The ratio of Th1-related gene expression level to that of Th2-related genes was inverted in common marmosets. We confirmed the inverted ratio of CD4 to CD8 in common marmosets by flow cytometric analysis. Therefore, the difference in Th1/Th2 balance between common marmosets and humans may affect host defense and/or disease susceptibility, which should be carefully considered when using common marmoset as an experimental model for biomedical research.

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“…These cells may exert effects also in the context of neurotrauma. For example, injection of DCs immunized with whole spinal cord homogenate improved outcomes after spinal cord injury in mice [52] and also higher mammals [53]. However, we did not find differences in the expression of the DC marker CD11c, either in naïve animals or after injury.…”

Section: Discussionmentioning

confidence: 60%

Genetic variability in the rat Aplec C-type lectin gene cluster regulates lymphocyte trafficking and motor neuron survival after traumatic nerve root injury

Lindblom¹,

Aeinehband²,

Parsa³

et al. 2013

J Neuroinflammation

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BackgroundC-type lectin (CLEC) receptors are important for initiating and shaping immune responses; however, their role in inflammatory reactions in the central nervous system after traumatic injuries is not known. The antigen-presenting lectin-like receptor gene complex (Aplec) contains a few CLEC genes, which differ genetically among inbred rat strains. It was originally thought to be a region that regulates susceptibility to autoimmune arthritis, autoimmune neuroinflammation and infection.MethodsThe inbred rat strains DA and PVG differ substantially in degree of spinal cord motor neuron death following ventral root avulsion (VRA), which is a reproducible model of localized nerve root injury. A large F2 (DAxPVG) intercross was bred and genotyped after which global expressional profiling was performed on spinal cords from F2 rats subjected to VRA. A congenic strain, Aplec, created by transferring a small PVG segment containing only seven genes, all C-type lectins, ontoDA background, was used for further experiments together with the parental strains.ResultsGlobal expressional profiling of F2 (DAxPVG) spinal cords after VRA and genome-wide eQTL mapping identified a strong cis-regulated difference in the expression of Clec4a3 (Dcir3), a C-type lectin gene that is a part of the Aplec cluster. Second, we demonstrate significantly improved motor neuron survival and also increased T-cell infiltration into the spinal cord of congenic rats carrying Aplec from PVG on DA background compared to the parental DA strain. In vitro studies demonstrate that the Aplec genes are expressed on microglia and upregulated upon inflammatory stimuli. However, there were no differences in expression of general microglial activation markers between Aplec and parental DA rats, suggesting that the Aplec genes are involved in the signaling events rather than the primary activation of microglia occurring upon nerve root injury.ConclusionsIn summary, we demonstrate that a genetic variation in Aplec occurring among inbred strains regulates both survival of axotomized motor neurons and the degree of lymphocyte infiltration. These results demonstrate a hitherto unknown role for CLECs for intercellular communication that occurs after damage to the nervous system, which is relevant for neuronal survival.

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Transplantation of dendritic cells promotes functional recovery from spinal cord injury in common marmoset

Cited by 23 publications

References 47 publications

Macrophage migration inhibitory factor (MIF) promotes cell survival and proliferation of neural stem/progenitor cells

Macrophage migration inhibitory factor (MIF) promotes cell survival and proliferation of neural stem/progenitor cells

Immune-Related Gene Expression Profile in Laboratory Common Marmosets Assessed by an Accurate Quantitative Real-Time PCR Using Selected Reference Genes

Genetic variability in the rat Aplec C-type lectin gene cluster regulates lymphocyte trafficking and motor neuron survival after traumatic nerve root injury

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