SDF-1α Facilitates Mesenchymal Stem Cells to Induce Regulatory B Cell Differentiation from Patients with Immune Thrombocytopenia

B cells play a central role in the pathogenesis of immune thrombocytopenia (ITP) by participating in humoral immunity. Meanwhile, regulatory B cells (Bregs), one subset of B cells, express negative regulatory effect on ITP. Mesenchymal stem cells (MSCs) have been demonstrated in the ability to induc...

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Main Authors: Zhe Chen, Shufen Zhou, Jianyun Li, Hui Li, Can Huang, Qin Guo, Tiantian Zhang, Bingya Yang, Chuanqing Tu, Chengshan Guo
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2021/3254488
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author Zhe Chen
Shufen Zhou
Jianyun Li
Hui Li
Can Huang
Qin Guo
Tiantian Zhang
Bingya Yang
Chuanqing Tu
Chengshan Guo
author_facet Zhe Chen
Shufen Zhou
Jianyun Li
Hui Li
Can Huang
Qin Guo
Tiantian Zhang
Bingya Yang
Chuanqing Tu
Chengshan Guo
author_sort Zhe Chen
collection DOAJ
description B cells play a central role in the pathogenesis of immune thrombocytopenia (ITP) by participating in humoral immunity. Meanwhile, regulatory B cells (Bregs), one subset of B cells, express negative regulatory effect on ITP. Mesenchymal stem cells (MSCs) have been demonstrated in the ability to induce immunosuppression, and stromal cell-derived factor-1α (SDF-1α) plays an important role in the migration and survival of MSCs. To investigate the mechanism of SDF-1α in controlling umbilical cord-derived MSCs (UC-MSCs) in inducing regulatory B cell differentiation of patients with ITP, we reconfirmed that SDF-1α promotes the proliferation of MSCs at the low doses of 0.05 μg/mL and 0.1 μg/mL but inhibits the proliferation and promotes the apoptosis of UC-MSCs at the high doses 0.5 μg/mL and 1 μg/mL; when UC-MSCs are cocultured with SDF-1α at 0.1 μg/mL, the decreased proportion of CD19+/CD24hi/CD38hi cells and IL-10-producing B cells (B 10 cell), considered as the Breg subset from ITP significantly enhanced, and the content of IL-10 in the supernatant is also obviously increased. The proportion of Bregs and the IL-10 secretion could be further promoted by the UC-MSCs treated with 0.1 μg/mL SDF-1α, which could also promote the miRNA-133 expression of UC-MSCs in an exosome-dependent manner; moreover, while the UC-MSCs were transfected with the miR-133 inhibitor, the proportion of induced Bregs decreased obviously when cocultured with peripheral blood mononuclear cells (PBMCs) of ITP. We conclude that UC-MSCs could effectively enhance the decreased proportion of Bregs from ITP; at appropriate concentrations, SDF-1α may promote the proliferating and survival ability of UC-MSCs and improve the production of Bregs induced by UC-MSCs through controlling miRNA-133 expression in the exosomes.
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spelling doaj-art-2ad7dab7ede940b69ac3739e49db3f732025-02-03T06:46:09ZengWileyStem Cells International1687-96782021-01-01202110.1155/2021/3254488SDF-1α Facilitates Mesenchymal Stem Cells to Induce Regulatory B Cell Differentiation from Patients with Immune ThrombocytopeniaZhe Chen0Shufen Zhou1Jianyun Li2Hui Li3Can Huang4Qin Guo5Tiantian Zhang6Bingya Yang7Chuanqing Tu8Chengshan Guo9Department of Rheumatology and ImmunologyDepartment of Rheumatology and ImmunologyDepartment of HematologyDepartment of Rheumatology and ImmunologyDepartment of HematologyDepartment of Rheumatology and ImmunologyDepartment of Rheumatology and ImmunologySpunolin Biotechnology Co.Department of HematologyDepartment of Rheumatology and ImmunologyB cells play a central role in the pathogenesis of immune thrombocytopenia (ITP) by participating in humoral immunity. Meanwhile, regulatory B cells (Bregs), one subset of B cells, express negative regulatory effect on ITP. Mesenchymal stem cells (MSCs) have been demonstrated in the ability to induce immunosuppression, and stromal cell-derived factor-1α (SDF-1α) plays an important role in the migration and survival of MSCs. To investigate the mechanism of SDF-1α in controlling umbilical cord-derived MSCs (UC-MSCs) in inducing regulatory B cell differentiation of patients with ITP, we reconfirmed that SDF-1α promotes the proliferation of MSCs at the low doses of 0.05 μg/mL and 0.1 μg/mL but inhibits the proliferation and promotes the apoptosis of UC-MSCs at the high doses 0.5 μg/mL and 1 μg/mL; when UC-MSCs are cocultured with SDF-1α at 0.1 μg/mL, the decreased proportion of CD19+/CD24hi/CD38hi cells and IL-10-producing B cells (B 10 cell), considered as the Breg subset from ITP significantly enhanced, and the content of IL-10 in the supernatant is also obviously increased. The proportion of Bregs and the IL-10 secretion could be further promoted by the UC-MSCs treated with 0.1 μg/mL SDF-1α, which could also promote the miRNA-133 expression of UC-MSCs in an exosome-dependent manner; moreover, while the UC-MSCs were transfected with the miR-133 inhibitor, the proportion of induced Bregs decreased obviously when cocultured with peripheral blood mononuclear cells (PBMCs) of ITP. We conclude that UC-MSCs could effectively enhance the decreased proportion of Bregs from ITP; at appropriate concentrations, SDF-1α may promote the proliferating and survival ability of UC-MSCs and improve the production of Bregs induced by UC-MSCs through controlling miRNA-133 expression in the exosomes.http://dx.doi.org/10.1155/2021/3254488
spellingShingle Zhe Chen
Shufen Zhou
Jianyun Li
Hui Li
Can Huang
Qin Guo
Tiantian Zhang
Bingya Yang
Chuanqing Tu
Chengshan Guo
SDF-1α Facilitates Mesenchymal Stem Cells to Induce Regulatory B Cell Differentiation from Patients with Immune Thrombocytopenia
Stem Cells International
title SDF-1α Facilitates Mesenchymal Stem Cells to Induce Regulatory B Cell Differentiation from Patients with Immune Thrombocytopenia
title_full SDF-1α Facilitates Mesenchymal Stem Cells to Induce Regulatory B Cell Differentiation from Patients with Immune Thrombocytopenia
title_fullStr SDF-1α Facilitates Mesenchymal Stem Cells to Induce Regulatory B Cell Differentiation from Patients with Immune Thrombocytopenia
title_full_unstemmed SDF-1α Facilitates Mesenchymal Stem Cells to Induce Regulatory B Cell Differentiation from Patients with Immune Thrombocytopenia
title_short SDF-1α Facilitates Mesenchymal Stem Cells to Induce Regulatory B Cell Differentiation from Patients with Immune Thrombocytopenia
title_sort sdf 1α facilitates mesenchymal stem cells to induce regulatory b cell differentiation from patients with immune thrombocytopenia
url http://dx.doi.org/10.1155/2021/3254488
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