The Immunomodulatory Potential of Wharton’s Jelly Mesenchymal Stem/Stromal Cells

Paladino, Fernanda Vieira; Rodrigues, Juliana de Moraes; Silva, Aline da; Goldberg, Anna Carla

doi:10.1155/2019/3548917

Cited by 37 publications

(30 citation statements)

References 79 publications

(83 reference statements)

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“…LG polypeptides stimulated UC -MSCs to reduce the release of a pro-inflammatory factor instability of the internal environment, and increase UC-MSCs immune regulation and regenerative biology, which conformed to the principle of the main pathogenesis of TCM. [ 23 , 30 ] This study showed that the improvement of HAQ, DAS28, ESR, CRP, RF, and Anti-CCP in the LG + UC -MSC group was significantly better than that in the UC -MSC group at 1 year after treatment (P < 0.05), and all patients conformed the ACR20 standard. This indicated that TCM intervention played an important role in anti-inflammation, regulating immunity and improving microcirculation in the treatment of UC-MSCs, which was beneficial to the migration of UC-MSCs and repair of damaged tissue.…”

Section: Discussionmentioning

confidence: 77%

“…Through the latter, MSC can regulate the immune response mediated by T cells, inhibit the production and function of various innate immune cells and play an anti-inflammatory role, regulate immunity and resist tissue injury. [ 23 ] Our previous study [ 18 ] has shown that UC- MSCs therapy for RA can reduce and alleviate the clinical symptoms of RA, and there is no significant change in human blood routine indicators, which showed good safety.…”

Section: Discussionmentioning

confidence: 99%

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Cervus and cucumis peptides combined umbilical cord mesenchymal stem cells therapy for rheumatoid arthritis

Qi¹,

Gao²,

Dang³

et al. 2020

Medicine

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Cervus and cucumis peptides (Lugua polypeptides, LG) are traditional Chinese medicine, which are active components of polypeptide extracted from Sika deer bone and melon seed, and they contain bone induced polypeptide biological factors. Umbilical cord mesenchymal stem cell, (UC-MSC) have tissue repair multiple effects, anti-inflammatory, and immune regulation function, which become a very promising start in rheumatoid arthritis (RA) treatment. Hence, LG combined UC-MSC can significantly enhance the UC-MSC treatment of rheumatoid arthritis (RA). To explore the clinical curative effect and therapeutic mechanism of LG combined UC-MSC for treating RA. 119 patients were divided into control and treatment groups, and both groups were treated with methotrexate tablets, leflunomide, and UC-MSC. But, LG were added to the treatment group. In vitro, the effects of LG on UC-MSC cell secretion of anti-inflammatory factors were also performed. The Health Assessment Questionnaire; the 28 joint disease activity score; C reactive protein; the erythrocyte sedimentation rate; rheumatoid factor; and anti-cyclic citrullinated peptide antibody were significantly reduced in treatment group 1 year after treatment ( P < .05). In vitro, compared with the control group, the number of hepatocyte growth factor (HGF), the secretion of prostaglandin E2 (PGE2) and tumor necrosis factor-inducible gene 6 protein (TSG6) increased significantly ( P < .05). LG combined UC-MSCs can significantly improve the curative effect of RA patients, while LG may reduce inflammatory cytokines, regulate immunity, improve microcirculation, and are conducive to UC-MSCs migration and the repair of damaged tissue.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Cervus and cucumis peptides combined umbilical cord mesenchymal stem cells therapy for rheumatoid arthritis

Qi¹,

Gao²,

Dang³

et al. 2020

Medicine

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“…Depending on the signals sensed by MSCs, they can migrate and home within a specific tissue. Indeed, MSCs are sensitive to shifts in the local milieu as they harbor a panel of receptors activating various signaling pathways (Paladino et al, 2019). We have previously shown that MSCs express several relevant receptors, such as the receptor for advanced glycation endproducts (RAGE), C-type lectin receptors (CLRs, including DECTIN-1, DECTIN-2 and MINCLE), leukotriene B4 (LTB4) receptors (BLT1 and BLT2) and cysteinyl leukotriene (CysLTs) receptors (CYSLTR1 and CYSLTR2) (Najar et al, 2018).…”

Section: Mscs Are Environmentally Responsivementioning

confidence: 99%

Mesenchymal Stromal Cell Immunology for Efficient and Safe Treatment of Osteoarthritis

Najar

Martel‐Pelletier

Pelletier

et al. 2020

Front. Cell Dev. Biol.

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Mesenchymal stem cell (MSC) therapy represents a promising approach for the treatment of osteoarthritis (OA). MSCs can be readily isolated from multiple sources and expanded ex vivo for possible clinical application. They possess a unique immunological profile and regulatory machinery that underline their therapeutic effects. They also have the capacity to sense the changes within the tissue environment to display the adequate response. Indeed, there is a close interaction between MSCs and the host cells. Accordingly, MSCs demonstrate encouraging results for a variety of diseases including OA. However, their effectiveness needs to be improved. In this review, we selected to discuss the importance of the immunological features of MSCs, including the type of transplantation and the immune and blood compatibility. It is important to consider MSC immune evasive rather than immune privileged. We also highlighted some of the actions/mechanisms that are displayed during tissue healing including the response of MSCs to injury signals, their interaction with the immune system, and the impact of their lifespan. Finally, we briefly summarized the results of clinical studies reporting on the application of MSCs for the treatment of OA. The research field of MSCs is inspiring and innovative but requires more knowledge about the immunobiological properties of these cells. A better understanding of these features will be key for developing a safe and efficient medicinal product for clinical use in OA.

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“…MSCs adopt a specific phenotype to suppress or promote immune responses depending on the inflammatory microenvironment in which they reside. Current studies on the immunomodulatory abilities of MSCs have focused on the interaction between MSCs and inflammatory monocytes [6,7]. Our previous studies have proven that a lower deployment of Ly6C high monocytes after AMI could improve the effectiveness of MSC transplantation and selectively ameliorate myocardial remodeling [8].…”

Section: Introductionmentioning

confidence: 99%

“…(b) Survival functions of C57BL/6 CX3CR1-/mice (red solid line) and C57BL/6 wild mice (blue dotted line) following MSC transplantation after AMI. Abbreviations: MSCs: mesenchymal stem cells 6. Stem Cells International…”

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confidence: 99%

MSCs Contribute to the Conversion of Ly6C^high Monocytes into Ly6C^low Subsets under AMI

Sheng

et al. 2020

Stem Cells International

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Background. Ly6Chigh monocytes are inflammatory cells that accumulate in an infarcted myocardium, and Ly6Clow monocytes are believed to be reparative and curb myocardial remodeling. NR4A1 is a novel target for modulating the inflammatory phenotype of monocytes during atherogenesis. Objectives. We aimed to investigate whether MSCs can contribute to the heterogeneity of Ly6Chigh monocytes differentiated into Ly6Clow monocytes and whether this regulation is related to nuclear receptor NR4A1. Methods. Ly6Chigh/low monocytes were first cocultured with MSCs. C57BL/6CX3CR1-/- mice and C57BL/6 wild-type mice were then used to construct AMI models, and survival functions in the two groups were further compared. Ly6Chigh/low monocytes in circulation and in MI tissue of C57BL/6CX3CR1-/- AMI mice with or without MSC transplantation were determined by flow cytometry at day 1 and day 3. NR4A1 expression was further determined by Western blot. Apoptosis of cardiac myocytes in the infarct border zone at day 3 and day 7 was identified by TUNEL kits. Angiogenesis in the AMI heart at day 7 and day 21 was determined through immunohistochemistry by CD31. Results. We first demonstrated that the percentage of Ly6Clow monocytes increased greatly after 3 days of coculture with MSCs (12.8%±3.77% vs. 3.69%±0.74%, p<0.001). The expression of NR4A1 in Ly6Chigh/low monocytes was also significantly elevated at that time (1.81±0.46 vs. 0.43±0.09, p<0.001). Following AMI, the percentage of circulating Ly6Clow monocytes in C57BL/6CX3CR1-/- mice was significantly lower than that in C57BL/6 wild-type mice (4.36%±1.27% vs. 12.17%±3.81%, p<0.001). The survival rate of C57BL/6CX3CR1-/- mice (25%) was significantly lower than that of C57BL/6 wild-type mice (56.3%) after AMI (χ2=4.343, p=0.037). After MSCs were transplanted, we observed a significant increase in Ly6Clow monocytes both in circulation (16.7%±3.67% vs. 3.22%±0.44%, p<0.001) and in the MI heart (3.31%±0.69% vs. 0.42%±0.21%, p<0.001) of C57BL/6CX3CR1-/- mice. Western blot analysis further showed that the expression level of NR4A1 in the MI hearts of C57BL/6CX3CR1-/- mice increased significantly under MSC transplantation (0.39±0.10 vs. 0.11±0.04, p<0.001). We also found significantly decreased TUNEL+ cardiac myocytes (15.45%±4.42% vs. 22.78%±6.40%, p<0.001) in mice with high expression levels of NR4A1 compared to mice with low expression levels. Meanwhile, we further identified increased capillary density in the infarct zones of mice with high expression levels of NR4A1 (0.193±0.036 vs. 0.075±0.019, p<0.001) compared to mice with low expression levels 21 days after AMI. Conclusions. MSCs can control the heterogeneity of Ly6Chigh monocyte differentiation into Ly6Clow monocytes and further reduce inflammation after AMI. The underlying mechanism might be that MSCs contribute to the increased expression of NR4A1 in Ly6Chigh/low monocytes.

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The Immunomodulatory Potential of Wharton’s Jelly Mesenchymal Stem/Stromal Cells

Cited by 37 publications

References 79 publications

Cervus and cucumis peptides combined umbilical cord mesenchymal stem cells therapy for rheumatoid arthritis

Cervus and cucumis peptides combined umbilical cord mesenchymal stem cells therapy for rheumatoid arthritis

Mesenchymal Stromal Cell Immunology for Efficient and Safe Treatment of Osteoarthritis

MSCs Contribute to the Conversion of Ly6C^high Monocytes into Ly6C^low Subsets under AMI

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The Immunomodulatory Potential of Wharton’s Jelly Mesenchymal Stem/Stromal Cells

Cited by 37 publications

References 79 publications

Cervus and cucumis peptides combined umbilical cord mesenchymal stem cells therapy for rheumatoid arthritis

Cervus and cucumis peptides combined umbilical cord mesenchymal stem cells therapy for rheumatoid arthritis

Mesenchymal Stromal Cell Immunology for Efficient and Safe Treatment of Osteoarthritis

MSCs Contribute to the Conversion of Ly6Chigh Monocytes into Ly6Clow Subsets under AMI

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MSCs Contribute to the Conversion of Ly6C^high Monocytes into Ly6C^low Subsets under AMI