Thalidomide corrects impaired mesenchymal stem cell function in inducing tolerogenic DCs in patients with immune thrombocytopenia

Ma, Ji; Ning, Yunna; Xu, Miao; Hou, Yu; Wang, Ning; Hou, Xiao-yan; Yu, Yanshan; Li, Hui; Wang, He; Shao, Liming; Zhou, Hai; Min, Yanan; Liu, Xinguang; Shi, Yan; Qin, Ping; Guo, Chengshan; Hou, Ming; Peng, Jun

doi:10.1182/blood-2013-03-491555

Cited by 22 publications

(15 citation statements)

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“…Targets of these key miRNAs showed enrichment in enzyme activities related to GO processes (activation of caspase activity; regulation of caspase, peptidase, and endopeptidase activities) in both ITP stages. These activities, especially those related to caspase, have been reported to be associated with ITP [37, 38]. Decreased expression of TRAIL, caspase-8, and caspase-3 in megakaryocytes after culture in plasma from patients with ITP, consistent with the inhibition of megakaryocyte apoptosis and reduced production of platelets, has been reported [39].…”

Section: Discussionsupporting

confidence: 54%

“…Decreased expression of TRAIL, caspase-8, and caspase-3 in megakaryocytes after culture in plasma from patients with ITP, consistent with the inhibition of megakaryocyte apoptosis and reduced production of platelets, has been reported [39]. Another study suggested that decreased caspase-8 and caspase-10 expression is related to the effects of thalidomide on mesenchymal stem cells, which may contribute to the pathogenesis of ITP [38]. …”

Section: Discussionmentioning

confidence: 65%

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Differential Expression of MiR-106b-5p and MiR-200c-3p in Newly Diagnosed Versus Chronic Primary Immune Thrombocytopenia Patients Based on Systematic Analysis

Qian

Yan

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) have been described to have important roles in primary immune thrombocytopenia (ITP). To gain additional understanding, we have now further evaluated the involvement of miRNAs in ITP. Methods: Microarray experiments were performed to examine the expression profiles of miRNAs and mRNAs in samples from subjects with newly diagnosed ITP (G1), chronic ITP (G2), and normal controls. The systematic Pipeline of Outlier MicroRNA Analysis framework was applied to identify key miRNAs expressed in the G1 and G2 samples. Quantitative PCR and receiver operator characteristic curves were used to confirm the performance of key miRNAs. Results: Compared with normal controls, 14 miRNAs (12 over-expressed and 2 under-expressed) and 7 over-expressed miRNAs were identified as key in G1 and G2 samples, respectively. miR-106b-5p, miR-200c-3p, and miR-92a-3p exhibited significantly different expression profiles among the groups. In particular, miR-106b-5p and miR-200c-3p were expressed at higher levels in patients with ITP compared to the normal controls. Furthermore, these two miRNAs expressions were even higher in patients with chronic ITP. Conclusion: MiR-106b-5p and miR-200c-3p may represent valuable biomarkers of ITP, although further studies are needed to confirm and assess the value of these potential biomarkers at various stages of ITP.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 65%

Differential Expression of MiR-106b-5p and MiR-200c-3p in Newly Diagnosed Versus Chronic Primary Immune Thrombocytopenia Patients Based on Systematic Analysis

Qian

Yan

et al. 2018

Cell Physiol Biochem

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“…These concerns were raised largely due to the observation of dysfunctionality and attenuated immunosuppressive properties of MSCs derived from patients with autoimmune ailments [13][14][15], although other studies failed to find such defects in related immune disorders [16][17][18]. Genome wide association studies have shown that single nucleotide polymorphisms (SNPs) predispose individuals to develop autoimmune disorders [19] and SNPs in the indoleamine 2,3-dioxygenase (IDO) gene have been shown to be associated with systemic sclerosis [20].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stromal Cells Derived From Crohn's Patients Deploy Indoleamine 2,3-dioxygenase-mediated Immune Suppression, Independent of Autophagy

Chinnadurai

Copland

et al. 2015

Molecular Therapy

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Autologous bone marrow-derived mesenchymal stromal cells (MSCs) for adoptive cell therapy of luminal Crohn's disease (CD) are being tested in clinical trials. However, CD is associated with dysregulation of autophagy and its effect on MSC's immunobiology is unknown. Here, we demonstrate no quantitative difference in phenotype, in vitro growth kinetics and molecular signatures to IFNγ between MSCs derived from CD and healthy individuals. CD MSCs were indistinguishable from those derived from healthy controls at inhibiting T-cell proliferation through an indoleamine 2,3-dioxygenase (IDO)-dependent mechanism. Upon IFNγ prelicensing, both MSC populations inhibit T-cell effector functions. Neither a single-nucleotide polymorphism (SNP) rs7820268 in the IDO gene, nor a widely reported CD predisposing SNP ATG16L1rs2241880 modulated the suppressive function of MSCs carrying these haplotypes. IFNγ stimulation or coculture with activated T cells upregulated the expression of autophagy genes and/or vacuoles on MSCs. Pharmacological blockade of autophagy pathway did not reverse the immunosuppressive properties and IFNγ responsiveness of MSCs confirming the absence of a functional link between these two cell biochemical properties. We conclude that autophagy, but not IDO and IFNγ responsiveness, is dispensable for MSC's immunosuppressive properties. MSCs from CD subjects are functionally analogous to those of healthy individuals.

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“…The thalidomide modulated MSCs from ITP patients induced mature DCs to become tolerogenic DCs. And the induction of tolerogenicity in DCs by MSCs was dependent on the expression of TIEG1in DCs[130]. Furthermore, recent experiments clearly documented the inhibitory effect irradiation on proliferation of MSCs, but does not impair the immunosuppressive capacity of BM-MSCs in vitro and thus might increase the safety of MSC-based cell products in clinical applications[131].…”

mentioning

confidence: 98%

Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases

Zhao¹,

Ren

Han

2016

Journal of Cellular Immunotherapy

257

200

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Mesenchymal stem cells (MSCs) represent a heterogenous population of adult,fibroblast-like multi-potent cells. MSCs have drawn much attention during the last decade in the field of regenerative medicine, mainly due to their capacity to differentiate into specific cell types, abundant production of soluble growth factors and cytokines, and hematopoiesis supporting properties. In addition, MSCs can migrate to the sites of inflammation and hold potent of immunomodulatory and anti-inflammatory effects through cell and cell interactions between MSCs and lymphocytes or production of soluble factors. Therefore, the application of MSCs in many disease situations is full of possibilities for future clinical treatment. Phase III clinical trials have been run using

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Thalidomide corrects impaired mesenchymal stem cell function in inducing tolerogenic DCs in patients with immune thrombocytopenia

Abstract: Key Points The impaired function of MSCs in proliferation ability and in inducing tolerogenic DCs may play a role in the pathogenesis of ITP. The effect of THD in correcting dysfunctions of MSCs may suggests a therapeutic potential of THD in ITP patients.

Cited by 22 publications

References 50 publications

Differential Expression of MiR-106b-5p and MiR-200c-3p in Newly Diagnosed Versus Chronic Primary Immune Thrombocytopenia Patients Based on Systematic Analysis

Differential Expression of MiR-106b-5p and MiR-200c-3p in Newly Diagnosed Versus Chronic Primary Immune Thrombocytopenia Patients Based on Systematic Analysis

Mesenchymal Stromal Cells Derived From Crohn's Patients Deploy Indoleamine 2,3-dioxygenase-mediated Immune Suppression, Independent of Autophagy

Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases

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