Mesenchymal Stem Cells in Autoimmune Disease

Background:Mesenchymal stem cells (MSCs) have a potential immunomodulatory role in autoimmune disease; however, the qualitative properties and haematopoietic support capacity of MSCs derived from patients with autoimmune disease is unclear.Objectives:To further characterise phenotypically and functionally bone marrow (BM)-derived MSCs from patients with systemic sclerosis (SSc).Methods:Key parameters of BM-derived MSC function and phenotype were assessed in 12 patients with SSc and compared with 13 healthy normal controls. The parameters included the ability to: form colony-forming unit fibroblasts (CFU-F), differentiate along the adipogenic and osteogenic lineages, express cell surface antigens defining the MSCs population, support normal haematopoiesis and suppress in vitro lymphocyte proliferation induced by either anti-CD3∊ plus anti-CD28 monoclonal antibodies or the mixed lymphocyte reaction.Results:SSc MSCs were shown to have a similar characteristic phenotype, capacities to form CFU-F and to differentiate along adipogenic and osteogenic lineages as those of healthy donor MSCs. The ability of SSc MSCs to support long-term haematopoiesis was also identical to that of controls. Both healthy donor and SSc BM MSCs reduced the proliferation of autologous and allogeneic peripheral blood mononuclear cells in a cell number dependent fashion.Conclusions:These results show that BM-derived MSCs from patients with SSc under the described culture conditions exhibit the same phenotypic, proliferative, differentiation potential and immunosuppressive properties as their healthy counterparts and could therefore be considered in an autologous setting. Further studies are needed to ensure the quality and safety of large-scale expansion of patient MSCs prior to their potential use in clinical trials.

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Human Olfactory Mesenchymal Stem Cells Are a Novel Candidate for Neurological Autoimmune Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2021.770884 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chongjun Xiao ◽

Di Lu ◽

Jinshuo Chen ◽

Xiaoyan Chen ◽

Huizhu Lin ◽

...

Keyword(s):

Stem Cells ◽

T Cells ◽

Mesenchymal Stem Cells ◽

Treatment Group ◽

Autoimmune Disease ◽

Functional Recovery ◽

Therapeutic Option ◽

Control Group ◽

Immune Disorder ◽

Ifn Γ

Background: Human olfactory mesenchymal stem cells (OMSC) have become a novel therapeutic option for immune disorder or demyelinating disease due to their immunomodulatory and regenerative potentials. However, the immunomodulatory effects of OMSC still need to be elucidated, and comparisons of the effects of different MSCs are also required in order to select an optimal cell source for further applications.Results: In animal experiments, we found neural functional recovery and delayed EAE attack in the OMSC treatment group. Compared with umbilical cord–derived mesenchymal stem cells (UMSC) treatment group and the control group, the OMSC treatment group had a better neurological improvement, lower serum levels of IFN-γ, and a lower proportion of CD4+IFN-γ+ T splenic lymphocyte. We also observed OMSC effectively suppressed CD4+IFN-γ+ T cell proportion in vitro when co-cultured with human peripheral blood–derived lymphocytes. The OMSC-mediated immunosuppressive effect on human CD4+IFN-γ+ T cells was attenuated by blocking cyclooxygenase activity.Conclusion: Our results suggest that OMSC treatment delayed the onset and promoted the neural functional recovery in the EAE mouse model possibly by suppressing CD4+IFN-γ+ T cells. OMSC transplantation might become an alternative therapeutic option for neurological autoimmune disease.

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Immunomodulation by mesenchymal stem cells in treating human autoimmune disease-associated lung fibrosis

Stem Cell Research & Therapy ◽

10.1186/s13287-016-0319-y ◽

2016 ◽

Vol 7 (1) ◽

Cited By ~ 18

Author(s):

Ming Liu ◽

Xiansheng Zeng ◽

Junli Wang ◽

Zhiping Fu ◽

Jinsong Wang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Autoimmune Disease ◽

Lung Fibrosis ◽

Human Autoimmune Disease

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Metformin enhances the immunomodulatory potential of adipose-derived mesenchymal stem cells through STAT1 in an animal model of lupus

Rheumatology ◽

10.1093/rheumatology/kez631 ◽

2020 ◽

Vol 59 (6) ◽

pp. 1426-1438 ◽

Cited By ~ 4

Author(s):

Se Gwang Jang ◽

Jaeseon Lee ◽

Seung-Min Hong ◽

Seung-Ki Kwok ◽

Mi-La Cho ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Autoimmune Disease ◽

Therapeutic Agent ◽

Therapeutic Agents ◽

Igg Antibody ◽

Inflammatory Phenotype ◽

Significant Disease ◽

Old Mice ◽

Immunomodulatory Potential

Abstract Objectives Mesenchymal stem cells (MSCs) are considered potential therapeutic agents for treating autoimmune disease because of their immunomodulatory capacities and anti-inflammatory effects. However, several studies have shown that there is no consistency in the effectiveness of the MSCs to treat autoimmune disease, including SLE. In this study, we investigated whether metformin could enhance the immunoregulatory function of MSCs, what mechanism is relevant, and whether metformin-treated MSCs could be effective in an animal lupus model. Methods Adipose-derived (Ad)-MSCs were cultured for 72 h in the presence of metformin. Immunoregulatory factors expression was analysed by real-time PCR and ELISA. MRL/lpr mice weekly injected intravenously with 1 × 106 Ad-MSCs or metformin-treated Ad-MSCs for 8 weeks. 16-week-old mice were sacrificed and proteinuria, anti-dsDNA IgG antibody, glomerulonephritis, immune complex, cellular subset were analysed in each group. Results Metformin enhanced the immunomodulatory functions of Ad-MSCs including IDO, IL-10 and TGF-β. Metformin upregulated the expression of p-AMPK, p-STAT1 and inhibited the expression of p-STAT3, p-mTOR in Ad-MSCs. STAT1 inhibition by siRNA strongly diminished IDO, IL-10, TGF-β in metformin-treated Ad-MSCs. As a result, metformin promoted the immunoregulatory effect of Ad-MSCs by enhancing STAT1 expression, which was dependent on the AMPK/mTOR pathway. Administration of metformin-treated Ad-MSCs resulted in significant disease activity improvement including inflammatory phenotype, glomerulonephritis, proteinuria and anti-dsDNA IgG antibody production in MRL/lpr mice. Moreover, metformin-treated Ad-MSCs inhibited CD4-CD8- T-cell expansion and Th17/Treg cell ratio. Conclusion Metformin optimized the immunoregulatory properties of Ad-MSCs and may be a novel therapeutic agent for the treatment of lupus.

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