2 min read

ID: 4655

Discovery Date: 28 September 2021, 00:49:36 UTC

Published Date: 2021-09-24 23:00:00

Source: BioMedCentral

Link: https://stemcellres.biomedcentral.com/articles/10.1186/s13287-021-02586-1

Manual Selection: true

Machine Learning Gaussian Naive Bayes Model: true

Abstract

Background: Considerable experimental and clinical evidences have proved that human umbilical cord mesenchymal stem cells (UC-MSCs) transplantation was powerful in systemic lupus erythematosus (SLE) treatment. MSCs could upregulate regulatory B cells (Bregs) in the mice model of the other immune disease. However, the regulation of MSCs on Bregs in SLE environment remains unclear.MethodsTo assess the abilities of UC-MSCs to treat SLE, MSCs were transferred intravenously to 17- to 18-week-old MRL/lpr mice. Four weeks later, mice were sacrificed. Survival rates, anti-dsDNA antibodies and renal histology were evaluated. CD4+ T helper (Th) cell subgroups and interleukin (IL)-10+ Bregs (B10) in the spleen were quantitated by flow cytometry. The changes of transforming growth factor (TGF)-β1, IL-6 and indoleamine 2,3-dioxyenase (IDO) mRNAs expressed by MSCs after co-cultured with B cells were detected using real-time polymerase chain reaction (RT-PCR). MSCs were infected by lentivirus carrying TGF-β1 shRNAs, then MSCs with low expression of TGF-β1 were conducted for co-culture in vitro and transplantation experiments in vivo.ResultsUC-MSCs transplantation could efficiently downregulate 24 h proteinuria and anti-dsDNA antibodies, correct Treg/Th17/Th1 imbalances and increase the frequency of B10 cells. The expression of TGF-β1 in MSCs was significantly increased after co-culture with B cells. Downregulation of TGF-β1 in MSCs could significantly attenuate the upregulation of B10 by MSCs in vitro and in vivo. Downregulation of TGF-β1 also compromised the immunomodulation effects of MSCs on Th17 and Treg cells and the therapeutic effects of MSC transplantation.ConclusionsUC-MSCs could protect against SLE in mice and upregulate IL-10+ Bregs via TGF-β1.

Noun Phrases in Title

  • Transplantation
  • mesenchymal stem cells
  • systemic lupus erythematosus
  • B10 cells
  • TGF-β1
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