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hUC-MSC transplantation therapy effects on lupus-prone MRL/lpr mice at early disease stages

BACKGROUND: The efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) transplantation in treating systemic lupus erythematosus (SLE) has been confirmed by small-scale clinical trials. However, these trials focused on severe or refractory SLE, while few studies focused on mild SLE. Therefo...

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Autores principales: Guo, Fengbiao, Pan, Quanren, Chen, Ting, Liao, Shuzhen, Li, Shangmei, Li, Aifen, Chen, Shuxian, Chen, Jiaxuan, Xiao, Zengzhi, Su, Hongyong, Yang, Lawei, Yang, Chen, Liu, Hua-feng, Pan, Qingjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10441722/
https://www.ncbi.nlm.nih.gov/pubmed/37605271
http://dx.doi.org/10.1186/s13287-023-03432-2
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author Guo, Fengbiao
Pan, Quanren
Chen, Ting
Liao, Shuzhen
Li, Shangmei
Li, Aifen
Chen, Shuxian
Chen, Jiaxuan
Xiao, Zengzhi
Su, Hongyong
Yang, Lawei
Yang, Chen
Liu, Hua-feng
Pan, Qingjun
author_facet Guo, Fengbiao
Pan, Quanren
Chen, Ting
Liao, Shuzhen
Li, Shangmei
Li, Aifen
Chen, Shuxian
Chen, Jiaxuan
Xiao, Zengzhi
Su, Hongyong
Yang, Lawei
Yang, Chen
Liu, Hua-feng
Pan, Qingjun
author_sort Guo, Fengbiao
collection PubMed
description BACKGROUND: The efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) transplantation in treating systemic lupus erythematosus (SLE) has been confirmed by small-scale clinical trials. However, these trials focused on severe or refractory SLE, while few studies focused on mild SLE. Therefore, this study focused on the therapeutic effects of hUC-MSC transplantation in early-stage or mild MRL/lpr lupus model mice. METHODS: Commercially available hUC-MSCs were transplanted into 8-week-old MRL/lpr mice by tail vein injection. Flow cytometry was used to analyze B cells and their subsets in the peripheral blood. Further, plasma inflammatory factors, autoantibodies, and plasma biochemical indices were detected using protein chip technology and ELISA kits. In addition, pathological staining and immunofluorescence were performed to detect kidney injury in mice. RESULTS: hUC-MSC transplantation did not affect the mice’s body weight, and both middle and high dose hUC-MSC transplantation (MD and HD group) actually reduced spleen weight. hUC-MSC transplantation significantly decreased the proportion of plasmablasts (PB), IgG1(−) PB, IgG1(+) PB, IgG1(+) memory B (MB) cells, IgG1(+) DN MB, and IgG1(+) SP MB cells. The hUC-MSC transplantation had significantly reduced plasma levels of inflammatory factors, such as TNF-α, IFN-γ, IL-6, and IL-13. Pathological staining showed that the infiltration of glomerular inflammatory cells was significantly reduced and that the level of glomerular fibrosis was significantly alleviated in hUC-MSC-transplanted mice. Immunofluorescence assays showed that the deposition of IgG and IgM antibodies in the kidneys of hUC-MSC-transplanted mice was significantly lower than in the control. CONCLUSION: hUC-MSC transplantation could inhibit the proliferation and differentiation of peripheral blood B cells in the early-stage of MRL/lpr mice, thereby alleviating the plasma inflammatory environment in mice, leading to kidney injury remission. The study provides a new and feasible strategy for SLE treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-023-03432-2.
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spelling pubmed-104417222023-08-22 hUC-MSC transplantation therapy effects on lupus-prone MRL/lpr mice at early disease stages Guo, Fengbiao Pan, Quanren Chen, Ting Liao, Shuzhen Li, Shangmei Li, Aifen Chen, Shuxian Chen, Jiaxuan Xiao, Zengzhi Su, Hongyong Yang, Lawei Yang, Chen Liu, Hua-feng Pan, Qingjun Stem Cell Res Ther Research BACKGROUND: The efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) transplantation in treating systemic lupus erythematosus (SLE) has been confirmed by small-scale clinical trials. However, these trials focused on severe or refractory SLE, while few studies focused on mild SLE. Therefore, this study focused on the therapeutic effects of hUC-MSC transplantation in early-stage or mild MRL/lpr lupus model mice. METHODS: Commercially available hUC-MSCs were transplanted into 8-week-old MRL/lpr mice by tail vein injection. Flow cytometry was used to analyze B cells and their subsets in the peripheral blood. Further, plasma inflammatory factors, autoantibodies, and plasma biochemical indices were detected using protein chip technology and ELISA kits. In addition, pathological staining and immunofluorescence were performed to detect kidney injury in mice. RESULTS: hUC-MSC transplantation did not affect the mice’s body weight, and both middle and high dose hUC-MSC transplantation (MD and HD group) actually reduced spleen weight. hUC-MSC transplantation significantly decreased the proportion of plasmablasts (PB), IgG1(−) PB, IgG1(+) PB, IgG1(+) memory B (MB) cells, IgG1(+) DN MB, and IgG1(+) SP MB cells. The hUC-MSC transplantation had significantly reduced plasma levels of inflammatory factors, such as TNF-α, IFN-γ, IL-6, and IL-13. Pathological staining showed that the infiltration of glomerular inflammatory cells was significantly reduced and that the level of glomerular fibrosis was significantly alleviated in hUC-MSC-transplanted mice. Immunofluorescence assays showed that the deposition of IgG and IgM antibodies in the kidneys of hUC-MSC-transplanted mice was significantly lower than in the control. CONCLUSION: hUC-MSC transplantation could inhibit the proliferation and differentiation of peripheral blood B cells in the early-stage of MRL/lpr mice, thereby alleviating the plasma inflammatory environment in mice, leading to kidney injury remission. The study provides a new and feasible strategy for SLE treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-023-03432-2. BioMed Central 2023-08-21 /pmc/articles/PMC10441722/ /pubmed/37605271 http://dx.doi.org/10.1186/s13287-023-03432-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Guo, Fengbiao
Pan, Quanren
Chen, Ting
Liao, Shuzhen
Li, Shangmei
Li, Aifen
Chen, Shuxian
Chen, Jiaxuan
Xiao, Zengzhi
Su, Hongyong
Yang, Lawei
Yang, Chen
Liu, Hua-feng
Pan, Qingjun
hUC-MSC transplantation therapy effects on lupus-prone MRL/lpr mice at early disease stages
title hUC-MSC transplantation therapy effects on lupus-prone MRL/lpr mice at early disease stages
title_full hUC-MSC transplantation therapy effects on lupus-prone MRL/lpr mice at early disease stages
title_fullStr hUC-MSC transplantation therapy effects on lupus-prone MRL/lpr mice at early disease stages
title_full_unstemmed hUC-MSC transplantation therapy effects on lupus-prone MRL/lpr mice at early disease stages
title_short hUC-MSC transplantation therapy effects on lupus-prone MRL/lpr mice at early disease stages
title_sort huc-msc transplantation therapy effects on lupus-prone mrl/lpr mice at early disease stages
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10441722/
https://www.ncbi.nlm.nih.gov/pubmed/37605271
http://dx.doi.org/10.1186/s13287-023-03432-2
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