Intrathecal delivery of human ESC-derived mesenchymal stem cell spheres promotes recovery of a primate EAE model
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ABSTRACT:
PROVIDER: PRJNA419161 | ENA |
REPOSITORIES: ENA
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Project description:Nonhuman primate experimental autoimmune encephalomyelitis (EAE) is a valuable model for multiple sclerosis an inflammatory demyelinating disease in the central nervous system (CNS). Human embryonic stem cell-derived mesenchymal stem cells (EMSC) are effective in treating murine EAE. Yet, it remains unknown whether the EMSC efficacy is translatable to humans. Here we induced a primate EAE model in cynomolgus monkeys and transported EMSC in spheres (EMSCsp) to preserve the cell viability under ambient conditions. First, single cells dissociated from EMSCsp were intravenously infused into normal and EAE monkeys. The cells reached various organs including CNS but diminished rapidly. To increase the number and viability of EMSC in the CNS, we injected EMSCsp intrathecally (i.t.) into the subarachnoid cavity of EAE monkeys multiple times post-onset and upon relapses during a 3-month observation. The clinical symptoms in these animals relieved rapidly following the injections and eventually disappeared. Whereas, symptoms in a vehicle control-injected EAE monkey remained and reduced slowly. Consistently, reduced lesions and active regeneration were found in the CNS of the EMSCsp-treated monkeys compared to the control. EMSC were found in the CNS long after the i.t. injections and some of the cells had differentiated into neurons and oligodendrocytes. Supporting evidence demonstrated that EMSCsp cultured in cerebrospinal fluid from the EAE monkeys largely converted to neural cells with elevated expression of genes for neuronal markers, neurotropic factors, and neuronal myelination. Together, this study suggests that i.t. injection of ambiently transported EMSCsp can treat EAE in nonhuman primates via remyelination and transdifferentiation, which shall expedite the clinical application of EMSC in patients.
2018-08-30 | GSE107145 | GEO
Project description:Nonhuman primate experimental autoimmune encephalomyelitis (EAE) is a valuable model for multiple sclerosis, an inflammatory demyelinating disease in the central nervous system (CNS). Human embryonic stem cell-derived mesenchymal stem cells (EMSC) are effective in treating murine EAE. Yet, it remains unknown whether the EMSC efficacy is translatable to humans. Here we induced a primate EAE model in cynomolgus monkeys and delivered EMSC in spheres (EMSCsp) to preserve the cell viability during long-distance transportation. EMSCsp intrathecally injected into the CNS, remarkably reduced the clinical symptoms, brain lesions, and neuronal demyelination in the EAE monkeys during a 3-month observation. Whereas, symptoms in the vehicle control-injected EAE monkey remained and reduced slowly and MRI lesions in brain expanded. Moreover, EMSC could transdifferentiate into neural cells in vivo in the CNS of the treated animals. Supporting evidence demonstrated that EMSCsp cells cultured in cerebrospinal fluid from the EAE monkeys largely converted to neural cells with elevated expression of genes for neuronal markers, neurotrophic factors, and neuronal myelination. Thus, this study demonstrates that EMSCsp injected directly into the CNS, can attenuate the disease progression in the primate EAE model, highly encouraging for clinical translation.
| S-EPMC6102276 | biostudies-literature
Project description:Genetic opticospinal EAE (OSE) and MOG-induced EAE (MOG-EAE) are two experimental autoimmune encephalomyelitis (EAE) mouse models of human multiple sclerosis. For the OSE model, double-transgenic 2D2 (TCRMOG) x IgHMOG mice were used. For MOG-EAE, wildtype C57BL/6 mice were immunized with a MOG peptide consisting of the amino acids 35-55, administered in complete Freund’s adjuvant containing 5mg / ml Mycobacterium tuberculosi. The severity of EAE was rated on the scale 0: healthy animal; 1: animal with a flaccid tail; [...]; 4: animal with both hind legs paralyzed. The case groups in the experiment were: OSE1: OSE with disease score 1; OSE4: OSE with disease score 4; MOG4: MOG-EAE injected with both MOG and adjuvant, with disease score 4. The control groups in the experiment were: OSE0: OSE with disease score 0; CFA: C57BL/6 mice injected only with adjuvant (no MOG); WT: Wildtype C57BL/6 mice. The aim of the experiment was to assess gene expression differences 1) between OSE4 and OSE0, 2) between OSE1 and OSE0, and 3) between MOG4 and CFA. For control, WT was compared to OSE0 and CFA. Subsequently, differentially expressed transcripts were compared, first, between the OSE4 vs. OSE0 and the MOG4 vs. CFA contrasts (different EAE models) and, second, between the OSE4 vs. OSE0 and the OSE1 vs. OSE0 contrasts (different EAE severity).
2020-08-21 | E-MTAB-9132 | biostudies-arrayexpress
Project description:In this study, we performed miRNA profiles analysis of 84, 17, 20, 83, 718, 1123, 528 and 816 glioma spheres compared to normal progenitor sample (16wf) using microarray to evaluate their potential role in regulation of the biological properties of proneural and mesenchymal glioma spheres
2016-07-07 | GSE84106 | GEO
Project description:Innate receptors, including Toll like receptors (TLRs), are implicated in pathogenesis of CNS inflammatory diseases such as multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). TLR response to pathogens or endogenous signals includes production of immunoregulatory mediators. One of these, interferon (IFN)β, a Type I IFN, plays a protective role in MS and EAE. We have previously shown that intrathecal administration of selected TLR ligands induced IFNβ and infiltration of blood-derived myeloid cells into the CNS, and suppressed EAE in mice. We have now extended these studies to evaluate a potential therapeutic role for CNS-endogenous TLR7 and TLR9. Intrathecal application of Imiquimod (TLR7 ligand) or CpG oligonucleotide (TLR9 ligand) into CNS of otherwise unmanipulated mice induced IFNβ expression, with greater magnitude in response to CpG. CNS extraparenchymal CD45+ cells were identified as source of IFNβ. Intrathecal CpG induced infiltration of monocytes, neutrophils, CD4+ T cells and NK cells whereas Imiquimod did not recruit blood-derived CD45+ cells. CpG, but not Imiquimod, had a beneficial effect on EAE, when given at time of disease onset. This therapeutic effect of CpG on EAE was not seen in mice lacking the Type I IFN receptor. In mice with EAE treated with CpG, the proportion of monocytes was significantly increased in the CNS. Infiltrating cells were predominantly localized to spinal cord meninges and demyelination was significantly reduced compared to non-treated mice with EAE. Our findings show that TLR7 and TLR9 signaling induce distinct inflammatory responses in the CNS with different outcome in EAE and point to recruitment of blood-derived cells and IFNβ induction as possible mechanistic links between TLR9 stimulation and amelioration of EAE. The protective role of TLR9 signaling in the CNS may have application in treatment of diseases such as MS.
2021-04-15 | GSE172083 | GEO
Project description:Gene expression in the CNS, comparing wild-type and TRPV1-/- mice with active EAE.
2012-08-03 | E-MEXP-3698 | biostudies-arrayexpress
Project description:Rhabomyosarcoma cells can be cultured in stem cell medium over several passages and form spheres being enriched in putative cancer stem cell markers and expressing high levels of stem cell genes. In this dataset, we include RNA samples from 2 rhabdomyosarcoma cell lines and 3 different sphere passages of each cell line. 16 samples were analyzed and all sphere passages were compared to the expression level of their corresponding adherent cell line. We wanted to see an up- or downregulation of genes in the spheres to identify new potential cancer stem cell marker.
2011-04-30 | E-GEOD-26635 | biostudies-arrayexpress
Project description:The aim of the experiment is to characterize the genetics and mechanisms of the inflammatory response after induction of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, by studying the genome wide expression in the spleen in late disease. A backcross was created between EAE-susceptible DA and EAE-resistant PVG rats. At day 35 after induction of EAE with myelin oligodendrocyte glycoprotein (MOG) in these rats, spleens were taken for transcriptional profiling.
2013-08-10 | E-MTAB-784 | biostudies-arrayexpress
Project description:mouse 4T1 breast cancer stem cell spheres were co-culutred with in vivo tumor antigen primed splenocytes, with in vivo tumor antigen primed splenocytes plus ex vivo reinforced activation via anti-CD3/CD28 beads or without co-culturing with splenocytes. Stem cell spheres were then collected and sunjected for gene expression analyses using RNA sequencing.
2022-04-06 | GSE199983 | GEO
Project description:In this study, we performed miRNA profiles analysis of 84, 17, 20, 83, 718, 1123, 528 and 816 glioma spheres compared to normal progenitor sample (16wf) using microarray to evaluate their potential role in regulation of the biological properties of proneural and mesenchymal glioma spheres miRNA profiling analysis of the 9 samples including 8 patient-derived samples including glioma sphere samples (84, 17, 20, 718, 816, 528, 83 and 1123), as well as one normal progenitor sample (16wf).
2016-07-07 | E-GEOD-84106 | biostudies-arrayexpress