Modulation of Mesenchymal Stem Cells-Mediated Adaptive Immune Effectors’ Repertoire in the Recovery of Systemic Lupus Erythematosus

Hoseinzadeh, Amin; Rezaieyazdi, Zahra; Afshari, Jalil Tavakol; Mahmoudi, Alireza; Heydari, Sahar; Moradi, Reza; Esmaeili, Seyed‐Alireza; Mahmoudi, Mahmoud

doi:10.1007/s12015-022-10452-7

Cited by 2 publications

(4 citation statements)

References 267 publications

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“…Hence, targeting MSCs and manipulating them may offer significant clinical benefits in the treatment outcome of SLE. Previous studies have shown improvements after allogenic MSC-based therapy in both mouse models of SLE and patients (reviewed in [ 3 , 14 ]). MSCs are the focus of extensive investigation as a natural biotreatment due to their unique features, including lack of immune activity, inherent ability to fight inflammation, and promote immunological tolerance [ 64 , 72 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, there was no significant difference regarding the infiltration of cells between N-MSCs, R-MSCs, and DR-MSCs treatment groups; however, potent reduction in the D-MSCs group, illustrating that immunomodulation by R-MSCs in advance has a much higher beneficial effect in reducing inflammation. Several studies have shown that MSCs can induce tolerance by direct effects and via mobilization of suppressor cell populations (reviewed in [ 14 ]). In explaining the higher population of infiltrating cells in mice treated with rhamnosus-pretreated MSC than D-MSCs, it can be suggested that R-MSCs may promote the mobilization of immune regulatory cells to the kidney, after that, they act in ameliorating tissue damage [ 90 ].…”

Section: Discussionmentioning

confidence: 99%

“…Researchers are learning to use engineered-MSCs as well as MSCs as direct or indirect payload carriers; however, considering undesirable side effects and their limitations, using immunoregulatory probiotics and/or their metabolites could be a new perspective. In this regard, of the unique characteristics of MSCs [ 14 ], we were actively looking for ways to increase the immunoregulatory activity of them. Current studies showed that MSCs express functional pattern recognition receptors and interact dynamically with various bacterial structures and their associated molecules [ 15 – 19 ].…”

Section: Introductionmentioning

confidence: 99%

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A new generation of mesenchymal stromal/stem cells differentially trained by immunoregulatory probiotics in a lupus microenvironment

Hoseinzadeh,

Mahmoudi,

Rafatpanah

et al. 2023

Stem Cell Res Ther

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Background Increasing evidence suggests that multipotent mesenchymal stem/stromal cells (MSCs) are a promising intervention strategy in treating autoimmune inflammatory diseases. It should be stated that systemic immunoregulation is increasingly recognized among the beneficial effects of MSCs and probiotics in treating morbid autoimmune disorders such as lupus. This study aimed to determine if immunoregulatory probiotics L. rhamnosus or L. delbrueckii can change the immunomodulatory effects of MSCs in lupus-like disease. Methods Pristane-induced lupus (PIL) mice model was created via intraperitoneal injection of Pristane and then confirmed. Naïve MSCs (N-MSCs) were coincubated with two Lactobacillus strains, rhamnosus (R-MSCs) or delbrueckii (D-MSCs), and/or a combination of both (DR-MSCs) for 48 h, then administrated intravenously in separate groups. Negative (PBS-treated normal mice) and positive control groups (PBS-treated lupus mice) were also investigated. At the end of the study, flow cytometry and enzyme-linked immunosorbent assay (ELISA) analysis were used to determine the percentage of Th cell subpopulations in splenocytes and the level of their master cytokines in sera, respectively. Moreover, lupus nephritis was investigated and compared. Analysis of variance (ANOVA) was used for multiple comparisons. Results Abnormalities in serum levels of anti-dsDNA antibodies, creatinine, and urine proteinuria were significantly suppressed by MSCs transplantation, whereas engrafted MSCs coincubation with both L. strains did a lesser effect on anti-dsDNA antibodies. L. rhamnosus significantly escalated the ability of MSCs to scale down the inflammatory cytokines (IFN-ɣ, IL-17), while L. delbrueckii significantly elevated the capacity of MSCs to scale down the percentage of Th cell subpopulations. However, incubation with both strains induced MSCs with augmented capacity in introducing inflammatory cytokines (IFN-ɣ, IL-17). Strikingly, R-MSCs directly restored the serum level of TGF-β more effectively and showed more significant improvement in disease parameters than N-MSCs. These results suggest that R-MSCs significantly attenuate lupus disease by further skew the immune phenotype of MSCs toward increased immunoregulation. Conclusions Results demonstrated that Lactobacillus strains showed different capabilities in training/inducing new abilities in MSCs, in such a way that pretreated MSCs with L. rhamnosus might benefit the treatment of lupus-like symptoms, given their desirable properties. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A new generation of mesenchymal stromal/stem cells differentially trained by immunoregulatory probiotics in a lupus microenvironment

Hoseinzadeh,

Mahmoudi,

Rafatpanah

et al. 2023

Stem Cell Res Ther

View full text Add to dashboard Cite

show abstract

“…These promising results suggest the possibility of a safer and more‐convenient combined biologic‐ and cell‐based therapy. Due to their anti‐inflammatory and immunomodulatory capabilities, several studies have reported the use of MSCs as a therapeutic strategy for treating autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, type I diabetes, and systemic lupus erythematosus (Hoseinzadeh et al, 2023; Liu et al, 2020; Xun et al, 2022; Zhang et al, 2022).…”

Section: Experimental Approaches Using Cell‐based Therapies For Sg Hy...mentioning

confidence: 99%

Recent progress in regenerative therapy for damaged salivary glands: From bench to bedside

et al. 2023

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ObjectiveFor functional restoration of salivary glands (SGs) injured by radiation therapy or Sjögren's syndrome (SS), various experimental approaches, such as gene therapy, tissue engineering, and cell‐based therapy, have been proposed. This narrative review summarized recent progresses in research using cell‐based therapies, including promising trials that could lead to bench‐to‐clinic applications.MethodsA literature review based on PubMed publications in the last two decades was performed to summarize progresses in cell‐based therapies for SG dysfunction.ResultsOver 100 experimental studies have shown the therapeutic potential of several types of cells, such as SG stem cells and mesenchymal stem cells, as well as effectively conditioned mononuclear cells, in both radiation injury and SS animal models. These therapies affect to slow fibrosis progression and stimulate tissue regeneration in atrophic glands. However, to date, only a total of seven studies have been developed to the stage of clinical study, showing the safety and preliminary efficacy.ConclusionTo lead the radical effectiveness expected in cell‐based therapy, advances in reverse translational research and in innovative experimental research, based on the findings of recent clinical studies, will be critical in the next decade.

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Modulation of Mesenchymal Stem Cells-Mediated Adaptive Immune Effectors’ Repertoire in the Recovery of Systemic Lupus Erythematosus

Cited by 2 publications

References 267 publications

A new generation of mesenchymal stromal/stem cells differentially trained by immunoregulatory probiotics in a lupus microenvironment

A new generation of mesenchymal stromal/stem cells differentially trained by immunoregulatory probiotics in a lupus microenvironment

Recent progress in regenerative therapy for damaged salivary glands: From bench to bedside

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