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

Fengbiao Guo; Quanren Pan; Ting Chen; Shuzhen Liao; Shangmei Li; Aifen Li; Shuxian Chen; Jiaxuan Chen; Zengzhi Xiao; Hongyong Su; Lawei Yang; Chen Yang; Hua-Feng Liu; Qingjun Pan

doi:10.1186/s13287-023-03432-2

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

Stem Cell Res Ther. 2023 Aug 21;14(1):211. doi: 10.1186/s13287-023-03432-2.

Authors

Fengbiao Guo^#¹, Quanren Pan^#¹, Ting Chen^#¹, Shuzhen Liao¹, Shangmei Li¹, Aifen Li¹, Shuxian Chen¹, Jiaxuan Chen¹, Zengzhi Xiao¹, Hongyong Su¹, Lawei Yang¹, Chen Yang¹, Hua-Feng Liu², Qingjun Pan³

Affiliations

¹ Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong, China.
² Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong, China. liuhf@gdmu.edu.cn.
³ Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong, China. pqj@gdmu.edu.cn.

^# Contributed equally.

Abstract

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.

Keywords: B cells; Immunosuppressive; Lupus mice; SLE; hUC-MSCs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Humans
Immunoglobulin G
Immunologic Factors
Kidney
Mesenchymal Stem Cell Transplantation*
Mice
Mice, Inbred MRL lpr

Substances

Immunologic Factors
Immunoglobulin G