Genetic contribution to mesenchymal stem cell dysfunction in systemic lupus erythematosus

Zhu, Yantong; Feng, Xuebing

doi:10.1186/s13287-018-0898-x

Cited by 31 publications

(25 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unfortunately, we failed to notice any significant changes in CD90 expression after three days exposure of HD/ASCs and RD/ASCs to TI stimulation (data not shown). Although this observation does not rule out the likelihood of CD90 loss due to the action of other factors contributing to chronic inflammation, alternative explanations, e.g., intrinsic defects, also exist [12].…”

Section: Discussionmentioning

confidence: 86%

“…However, depending on local conditions, tissue-resident MSCs can exhibit either anti-or pro-inflammatory capabilities, and thus may exert either protective effects or contribute to disease development [9]. In SLE and SSc, a growing body of data indicates numerous abnormalities of bone marrow derived MSCs (BM-MSCs), suggesting their possible contribution to disease pathology and raising questions about their autologous therapeutic application [10][11][12][13]. The knowledge about BM-MSC biology in AS is much less; limited data show aberrant function of these cells, and therefore several ongoing clinical trials apply allogenic MSCs [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Phenotype and Secretory Activity of Adipose-Derived Mesenchymal Stem Cells (ASCs) of Patients with Rheumatic Diseases

Kuca-Warnawin

Skalska

Janicka

et al. 2019

Cells

View full text Add to dashboard Cite

Mesenchymal stem/stromal cells (MSCs) have immunosuppressive and regenerative properties. Adipose tissue is an alternative source of MSCs, named adipose-derived mesenchymal stem cells (ASCs). Because the biology of ASCs in rheumatic diseases (RD) is poorly understood, we performed a basic characterization of RD/ASCs. The phenotype and expression of adhesion molecules (intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1) on commercially available healthy donors (HD), ASC lines (n = 5) and on ASCs isolated from patients with systemic lupus erythematosus (SLE, n = 16), systemic sclerosis (SSc, n = 17) and ankylosing spondylitis (AS, n = 16) were analyzed by flow cytometry. The secretion of immunomodulatory factors by untreated and cytokine-treated ASCs was measured by ELISA. RD/ASCs have reduced basal levels of CD90 and ICAM-1 expression, correlated with interleukin (IL)-6 and transforming growth factor (TGF)-β1 release, respectively. Compared with HD/ASCs, untreated and tumour necrosis factor (TNF) + interferon (IFN)-γ (TI)-treated RD/ASCs produced similar amounts of prostaglandin E2 (PGE2), IL-6, leukemia inhibiting factor (LIF), and TGF-β1, more IL-1Ra, soluble human leukocyte antigen G (sHLA-G) and tumor necrosis factor-inducible gene (TSG)-6, but less kynurenines and galectin-3. Basal secretion of galectin-3 was inversely correlated with the patient’s erythrocyte sedimentation rate (ESR) value. IFN-α and IL-23 slightly raised galectin-3 release from SLE/ASCs and AS/ASCs, respectively. TGF-β1 up-regulated PGE2 secretion by SSc/ASCs. In conclusion, RD/ASCs are characterized by low basal levels of CD90 and ICAM-1 expression, upregulated secretion of IL-1Ra, TSG-6 and sHLA-G, but impaired release of kynurenines and galectin-3. These abnormalities may modify biological activities of RD/ASCs.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

The Phenotype and Secretory Activity of Adipose-Derived Mesenchymal Stem Cells (ASCs) of Patients with Rheumatic Diseases

Kuca-Warnawin

Skalska

Janicka

et al. 2019

Cells

View full text Add to dashboard Cite

show abstract

“…Because of the differentiation and immunoregulatory capacity of MSCs, their dysfunction has been proposed as the mediating mechanism in a wide variety of disease states. Shifts in the fate choice of MSCs, reduction in their overall proliferative capacity or in their differentiation to a particular cell type, as well as their role in mediating the activity of other cell populations have been demonstrated to play varying roles in disease progression [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Impact of Type 2 Diabetes Mellitus on Human Bone Marrow Stromal Cell Number and Phenotypic Characteristics

Cassidy

Shortiss

Murphy

et al. 2020

IJMS

View full text Add to dashboard Cite

Human bone marrow-derived mesenchymal stromal cells (MSCs) have been investigated in numerous disease settings involving impaired regeneration because of the crucial role they play in tissue maintenance and repair. Considering the number of comorbidities associated with type 2 diabetes mellitus (T2DM), the hypothesis that MSCs mediate these comorbidities via a reduction in their native maintenance and repair activities is an intriguing line of inquiry. Here, it is demonstrated that the number of bone marrow-derived MSCs in people with T2DM was reduced compared to that of age-matched control (AMC) donors and that this was due to a specific decrease in the number of MSCs with osteogenic capacity. There were no differences in MSC cell surface phenotype or in MSC expansion, differentiation, or angiogenic or migratory capacity from donors living with T2DM as compared to AMCs. These findings elucidate the basic biology of MSCs and their potential as mediators of diabetic comorbidities, especially osteopathies, and provide insight into donor choice for MSC-based clinical trials. This study suggests that any role of bone marrow MSCs as a mediator of T2DM comorbidity is likely due to a reduction in the osteoprogenitor population size and not due to a permanent alteration to the MSCs’ capacity to maintain tissue homeostasis through expansion and differentiation.

show abstract

“…A previous study has reported that a decrease in circulating T-reg cells may promote the appearance of autoreactive T-and B-cells, the loss of homeostasis, and immune system failure, which is associated with SLE occurrence 5 . Another study reported that the enhancement of T-reg cell functions may have useful effects for human SLE 6 , and an SLE treatment that is currently being developed is the transplantation of mesenchymal stem cells (MSCs) 7 . MSCs are nonhematopoietic, plastic-adherent, multipotent, and fibroblastic-like cells that may express several surface markers, such as CD90, CD105, CD44, CD73, and lack the expression others, such as CD79, CD19, CD14, CD11b, CD45, CD34, and human leukocyte antigen (HLA)-DR 8 .…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells Induce Regulatory T-cell Population in Human SLE

Ikhsan

Putra

Munir

et al. 2020

Bangladesh J Med Sci

View full text Add to dashboard Cite

Background: The mechanisms underlying peripheral disorders during systemic lupus erythematosus (SLE) were found to be shared with tolerance disorders and mediated by T-regulator (T-reg) cells. Mesenchymal stem cells (MSCs) may inhibit T-cell subset differentiation and induce the T-reg cell phenotype. However, the capacity of MSCs to promote functional T-reg cells in SLE patients remains unclear. Objectives: This study aimed to analyze the capacity of MSCs to induce the production of functional CD4+ CD25+ Foxp3+ T-reg cells, in vitro, under co-culture conditions with human SLE cells. Methods: This study used a pre- and post-test control group design. Peripheral blood mononuclear cells (PBMCs) were extracted from SLE patients at the Kariadi Hospital, and MSCs were derived from human umbilical cords (hUCs) The PBMC control group was treated with standard medium, and the treatment group was co-cultured with hUC-MSCs. After 24 hours of co-culture incubation, T-reg cells were removed from the PBMC pool, using magnetic-activated cell sorting (MACS), and the population was assessed using the trypan blue exclusion assay. Results: A significant increase in the population of T-reg cells was observed (P < 0.001) after 24 hours of co-culture incubation with hUC-MSCs. Conclusion: This study concluded that MSCs have the capacity to enhance the T-reg population in human SLE PBMCs. Bangladesh Journal of Medical Science Vol.19(4) 2020 p.743-748

show abstract

Genetic contribution to mesenchymal stem cell dysfunction in systemic lupus erythematosus

Cited by 31 publications

References 67 publications

The Phenotype and Secretory Activity of Adipose-Derived Mesenchymal Stem Cells (ASCs) of Patients with Rheumatic Diseases

The Phenotype and Secretory Activity of Adipose-Derived Mesenchymal Stem Cells (ASCs) of Patients with Rheumatic Diseases

Impact of Type 2 Diabetes Mellitus on Human Bone Marrow Stromal Cell Number and Phenotypic Characteristics

Mesenchymal Stem Cells Induce Regulatory T-cell Population in Human SLE

Contact Info

Product

Resources

About