scholarly journals Mesenchymal Stem Cells Enhance Therapeutic Effect and Prevent Adverse Gastrointestinal Reaction of Methotrexate Treatment in Collagen-Induced Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qiming Zhai ◽  
Jiayi Dong ◽  
Xuesi Zhang ◽  
Xiaoning He ◽  
Dongdong Fei ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Side Effects ◽  
Adverse Events ◽  
Therapeutic Effect ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis ◽  
Combined Application ◽  
Raw264.7 Macrophages

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by articular destruction and functional loss. Methotrexate (MTX) is effective in RA treatment. However, MTX induces several adverse events and 20%-30% of patients do not respond to MTX. Thus, it is urgent to enhance the therapeutic effects and reduce the side effects of MTX. Recent studies showed that mesenchymal stem cells (MSCs) were participants in anti-inflammation, immunoregulation, and tissue regeneration. However, whether the combined application of MSCs and MTX promotes the therapeutic effects and reduces the side effects of MTX has not been studied. In this study, we used bovine type II collagen to induce rheumatoid arthritis in mice (collagen-induced arthritis, CIA). Then, CIA mice were subjected to MTX or MSC treatment, or both. The therapeutic effect and adverse events of different treatments on RA were evaluated with micro-CT, HE staining, and immunohistochemistry in vivo. Apoptosis and proliferation of MODE-K cells were measured after treated with MTX or/and cocultured with UCs. To test M2 polarization, Raw264.7 macrophages were stimulated by MTX with different concentrations or cocultured with UCs. We found that the combined application of MSCs and MTX increased the therapeutic effects on RA, as evidenced by decreased arthritis score, inflammatory responses, and mortality. Moreover, in this combination remedy, MTX prefers to suppress inflammation by facilitating macrophage polarization to M2 type while UCs prefer to eliminate gastrointestinal side effects of MTX via mitigating the apoptosis of intestinal epithelial cells. Thus, a combination of MTX and UCs is a promising strategy for RA treatment.

scholarly journals Comparison of therapeutic effects of different mesenchymal stem cells on rheumatoid arthritis in mice

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7023 ◽  
Author(s):  
Qing Zhang ◽  
Qihong Li ◽  
Jun Zhu ◽  
Hao Guo ◽  
Qiming Zhai ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Effect ◽  
Joint Destruction ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Therapeutic Effects ◽  
Micro Ct ◽  
Tnf Α

Background Rheumatoid arthritis (RA) is a chronic and nonspecific autoimmune disease, which leads to joint destruction and deformity. To investigate the potential of human mesenchymal stem cells (MSCs) as a new therapeutic strategy for patients with RA, we compared the therapeutic effects of bone marrow derived MSCs (BMSCs), umbilical cord derived MSCs (UCs), and stem cells derived from human exfoliated deciduous teeth (SHED) on collagen-induced arthritis (CIA) in mice. Methods A total of 24 DBA/1 mice were infused with type II collagen to induce RA in the experimental model. MSC-treated mice were infused with UCs, BMSCs, and SHED, respectively. Bone erosion and joint destruction were measured by micro-computed tomographic (micro-CT) analysis and hematoxylin and eosin staining. The levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were measured by immunohistochemistry and Enzyme-Linked Immunosorbent Assay (ELISA). Results Systemic delivery of MSCs significantly improved the severity of the symptoms related to CIA to greater extent compared with the untreated control group. Micro-CT revealed reduced bone erosions in the metatarsophalangeal joints upon treatment with MSCs. Additionally, according to histologic evaluation, reduced synovitis and articular destruction were observed in MSC-treated groups. The levels of TNF-α and IL-1β in the serum and joints decreased with treatment by MSCs. Conclusion Our findings suggest that systemic infusion of UCs, BMSCs, and SHED may significantly alleviate the effects of RA. The therapeutic effect of BMSCs was greater than that of SHED, while the UCs were shown to have the best therapeutic effect on CIA mice. In conclusion, compared with BMSCs and SHED, UCs may be a more suitable source of MSCs for the treatment of patients with RA.

scholarly journals IL-10 Gene-Modified Human Amniotic Mesenchymal Stem Cells Augment Regenerative Wound Healing by Multiple Synergistic Effects

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Shune Xiao ◽  
Guangtao Huang ◽  
Zairong Wei ◽  
Kaiyu Nie ◽  
Zhiyuan Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Effect ◽  
Synergistic Effects ◽  
Biological Effects ◽  
Therapeutic Effects ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Amniotic Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) possess a capacity to enhance cutaneous wound healing that is well characterized. However, the therapeutic effect of MSCs appears to be limited. Modifying MSC target genes to increase necessary biological effects is a promising strategy for wound therapy. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has a therapeutic effect on wound healing. In this study, we modified human amniotic mesenchymal stem cells (hAMSCs) using recombinant lentiviral vectors for expressing IL-10 and evaluated the therapeutic effects of hAMSCs-IL-10 in wound healing. We elucidated the mechanisms underlying the effects. We found that promoting wound healing was maintained by synergistic effects of hAMSCs and IL-10. hAMSCs-IL-10 showed stronger biological effects in accelerating wound closure, enhancing angiogenesis, modulating inflammation, and regulating extracellular matrix remodeling than hAMSCs. hAMSCs-IL-10 would be better at promoting wound healing and improving healing quality. These data may provide a theoretical foundation for clinical administration of hAMSCs-IL-10 in cutaneous wound healing and skin regeneration.

scholarly journals Therapeutic Effect of Exogenous Regulatory T Cells on Collagen-induced Arthritis and Rheumatoid Arthritis

2020 ◽  
Vol 29 ◽  
pp. 096368972095413
Author(s):  
Shutong Li ◽  
Hongxing Wang ◽  
Hui Wu ◽  
Xiaotian Chang
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
Cell Transplantation ◽  
Treg Cell ◽  
Therapeutic Effect ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Treg Cells ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis

Regulatory T (Treg) cells have anti-inflammatory functions and heighten immune tolerance. The proportion and functions of Treg cells are perturbed in rheumatoid arthritis (RA), contributing to the excessive immune activation associated with this disease. We therefore hypothesized that supplementation with foreign Treg cells could be used to treat RA. To investigate the therapeutic effects of exogenous Treg cells on RA and its mechanism, we used human Treg cells to treat collagen-induced arthritis (CIA) in a rat model to observe whether exogenous Treg cells can treat the disease across species. Successful treatment would indicate that Treg cell transplantation in humans is more likely to affect RA. In the present study, human Treg cells were collected from healthy human peripheral blood and culture-expanded in vitro. Induced human Treg cells were injected into CIA rats via the tail vein. The rats’ lymphocyte subtypes, cytokines, and Th1/Th2 ratios were measured using flow cytometry. In the rats, following injection of the human Treg cells, the severity of CIA was significantly reduced ( P < 0.01), the proportion of endogenous Treg cells increased in the peripheral blood and spleen ( P = 0.007 and P < 0.01, respectively), and the proportion of B cells decreased ( P = 0.031). The IL-5 level, IL-6 level, and Th1/Th2 ratio in the peripheral blood were decreased ( P = 0.013, 0.009, and 0.012, respectively). The culture-expanded human Treg cells were also cultured with synovial fibroblast cells from RA patients (RASFs). After coculture with Treg cells, RASFs showed reduced proliferation ( P < 0.01) and increased apoptosis ( P = 0.037). These results suggest that exogenous and induced Treg cells can produce a therapeutic effect in RA and CIA by increasing endogenous Treg cells and RASF apoptosis and reducing B cells, the Th1/Th2 ratio, and secretion levels of IL-5 and IL-6. Treg cell transplantation could serve as a therapy for RA that does not cause immune rejection.

scholarly journals Preclinical Evaluation of a Single Intravenous Infusion of hUC-MSC (BX-U001) in Rheumatoid Arthritis

2020 ◽  
Vol 29 ◽  
pp. 096368972096589
Author(s):  
Linan Liu ◽  
Henry P. Farhoodi ◽  
Menglu Han ◽  
Guangyang Liu ◽  
Jingxia Yu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intravenous Infusion ◽  
Rate Of Change ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Therapeutic Benefits ◽  
Significant Difference ◽  
Single Intravenous Infusion

Rheumatoid arthritis (RA) is an inflammatory disease of the joints, which causes severe pain and excessive systemic circulation of harmful inflammatory cytokines. Current treatments are limited, with some patients not responding well, and some experiencing severe and detrimental side effects. Mesenchymal stem cells (MSC) are cell-based therapeutics being evaluated as potent immunomodulators in RA and may provide relief to patients not responding well to drug-based treatments. We evaluated the safety and efficacy of BX-U001 human umbilical cord tissue–derived mesenchymal stem cells (hUC-MSC) to treat RA, in support of a successful investigational new drug application. A collagen-induced arthritis (CIA) mouse model of RA was established in DBA/1 J mice. Mice from the treatment assessment group were given a tail vein infusion of hUC-MSC 24 days after primary RA induction, while control assessment (CA) group mice were given cell-free carrier solution. All animals were evaluated daily for RA symptoms via clinical scoring, blood was taken periodically for cytokine analysis, and mice were dissected at end point for histological analysis. A linear mixed model was used to compare the rate of change among groups. The clinical scores of TA group were significantly reduced compared with CA group ( P < 0.01), indicating therapeutic effects. The histological scores of the joints in TA group were significantly lower than those in the CA group ( P < 0.05), but had no significant difference compared with Healthy groups ( P > 0.05). The concentration of (interleukin) IL-6 in TA group was significantly reduced by 80.0% ( P < 0.0001) 2 days after treatment and by 93.4% at the experimental endpoint compared with levels prior to hUC-MSC injection. A single intravenous infusion of hUC-MSC (2 × 106 cells/mouse), to CIA-induced DBA/1 J mice, resulted in significant alleviation of RA symptoms and may provide significant therapeutic benefits in humans.

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