Induction therapy with mesenchymal stromal cells in kidney transplantation: a meta-analysis
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Abstract Objective The aim of this meta-analysis was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) versus traditional regimens for induction therapy in kidney transplantation (KT), especially the safety of MSC infusion, practicability of MSCs as induction therapy agents, and posttransplant complications. Methods PubMed, Embase, EBSCO, Ovid, and the Cochrane Library were searched for prospective clinical trials that compared MSCs with traditional regimens for induction therapy in KT. Results Four trials were included, including a total of 197 patients. The pooled results revealed that MSC therapy had a lower 1-year infection rate than did the traditional therapies (RR = 0.65, 95% CI: 0.46–0.9, P = 0.01). There were no significant differences between the two protocols regarding the 1-year acute rejection (AR) rate (RR = 0.77, 95% CI: 0.41–1.45, P = 0.42), 1-year graft survival rate (RR = 0.99, 95% CI: 0.95–1.03, P = 0.74), delayed graft function (DGF) rate (RR = 0.54, 95% CI: 0.21–1.38, P = 0.2) and renal graft function at 1 month (MD = −1.56, 95% CI: − 14.2–11.08, p = 0.81), 3 months (MD = 0.15, 95% CI: − 5.63–5.93, p = 0.96), 6 months (MD = − 1.95, 95% CI: − 9.87–5.97, p = 0.63), and 12 months (MD = − 1.13, 95% CI: − 7.16–4.89, p = 0.71) postsurgery. Subgroup analysis demonstrated that the 1-year AR rate, 1-year graft survival rate, DGF rate, and renal graft function at 12 months postsurgery did not significantly differ between the low-dose calcineurin inhibitor (CNI) group and the standard-dose CNI group, indicating the potential benefits of successful CNI sparing in combination with MSC treatment. Moreover, when MSCs were applied as an alternative therapy rather than an additional therapy or allogeneic MSCs were utilized instead of autologous MSCs, all of the outcomes mentioned above were comparable. Conclusion Induction therapy with MSCs is safe and has similar immune response modulation effects to those of traditional regimens in the short term in KT recipients. However, regarding the long-term effects, as suggested by the 1-year infection rate and the potential of CNI sparing, MSC therapy has significant advantages. However, these advantages should be further verified in more well-designed, multicenter randomized controlled trials (RCTs) with large sample sizes and long follow-up periods.Keywords:
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Objective: The primary purpose of our study is to systemically evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) on recovery of dysphagia after stroke. Search Methods: We searched randomized controlled trials (RCTs) and non-RCTs published by PubMed, the Cochrane Library, ScienceDirect, MEDLINE, and Web of Science from inception until April 24, 2021. Language is limited to English. After screening and extracting the data, and evaluating the quality of the selected literature, we carried out the meta-analysis with software RevMan 5.3 and summarized available evidence from non-RCTs. Results: Among 205 potentially relevant articles, 189 participants (from 10 RCTs) were recruited in the meta-analysis, and six non-RCTs were qualitatively described. The random-effects model analysis revealed a pooled effect size of SMD = 0.65 (95% CI = 0.04-1.26, p = 0.04), which indicated that rTMS therapy has a better effect than conventional therapy. However, the subgroup analysis showed that there was no significant difference between low-frequency and high-frequency groups. Even more surprisingly, there were no statistically significant differences between the two groups and the conventional training group in the subgroup analysis, but the combined effect was positive. Conclusion: Our study suggests that rTMS might be effective in treating patients with dysphagia after stroke.
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Mesenchymal stromal cells derived from amnion (AM-MSCs) can be easily obtained in large quantity by less invasive method in comparison to bone marrow-derived MSCs (BM-MSCs). However, the biological and immunosuppressive properties of AM-MSCs are still poorly characterized. Previous studies demonstrated that BM-MSCs expressed indoleamine 2,3-dioxygenase (IDO) to suppress T-cell responses. This study was designed to address whether IDO contributes to the immunosuppressive function of AM-MSCs. MSCs isolated from amnion were cultured in complete medium similar to BM-MSCs. After culture, AM-MSCs exhibited spindle shape morphology and expressed MSC markers similar to that of BM-MSCs. In addition, AM-MSCs were able to differentiate into adipocytes and osteoblasts. Fascinatingly, AM-MSCs and BM-MSCs exhibited comparable degree of immunosuppressive effect when they were co-cultured with activated T-cells. In addition, IDO secreted by AM-MSCs was responsible for induction of immunosuppressive activities in the same manner as BM-MSCs. Taken together; the results of the present study demonstrate that while AM-MSCs and BM-MSCs show similar immunosuppressive effect, AM-MSCs may have additional advantage over the BM-MSCs in terms of availability. Therefore, AM-MSCs might be considered a potential source for therapeutic applications especially for treatment of immune related diseases.
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Objective To compare the efficacy of intracavernosal injection of autologous and allogeneic mesenchymal stem cells as potential treatment of erectile dysfunction in an experimental rat model. Methods Mesenchymal stem cells were isolated from rat paratesticular fat tissue. Bilateral cavernous nerve injury was carried out followed by immediate intracavernosal injection of either autologous or allogeneic mesenchymal stem cells or mesenchymal stem cell lysates. One month after injection, erectile function was evaluated by means of intracavernosal pressure measurement. All rats were eventually killed, and penile tissues were taken for immunhistochemical and molecular investigation. Results A total of 36 S prague– D awley rats were used. The mean maximum intracavernosal pressure in the sham‐operated, autologous and allogeneic mesenchymal stem cell injection groups were significantly better compared with the vehicle injection group (80.5 [3.56], 71.1 [2.9] and 69.2 [3.2] vs 40.33 [4.4], respectively). Mean maximum intracavernosal pressure to mean arterial pressure ratios in the autologous and allogeneic mesenchymal stem cell and mesenchymal stem cell lysate injection groups were not significantly different. Conclusions Intracavernosal injection of both autologous or allogeneic mesenchymal stem cells improve erectile functions in a rat model of cavernous nerve injury. Allogeneic mesenchymal stem cells might provide clinicians with ready to use, standardized and, in certain cases, more effective products. More studies focusing on long‐term immunological aspects of allogeneic mesenchymal stem cells are required.
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The results of recent clinical trials using mesenchymal stem cells (MSCs) have been unsatisfactory, indicating that current MSC-based therapies need to be improved. We and others have previously demonstrated that MSCs activate complement by unknown mechanisms after infusion, leading to damaged MSCs. In the study reported here, we found that incorporation of N-glycolylneuraminic acid onto MSCs during in vitro culture was a factor in the activation of complement by MSCs. In addition, we developed a way to "paint" heparin onto MSCs. This novel method improved the viability of MSCs and enhanced their function after infusion by directly inhibiting complement and by recruiting factor H, another potent complement inhibitor in serum, onto the surface of the MSCs. These data suggest that cell-surface engineering of MSCs with heparin to locally inhibit complement activation on MSCs might be a straightforward and effective method for improving the outcome of current MSC-based therapies.
Complement
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Objective
To systematically assess the efficacy and safety of Kanglaite combined with chemotherapy on advanced non-small cell lung cancer compared with chemotherapy alone.
Methods
We searched systematically literatures from Medline, Embase, Cochrane Library, Web of Science, CBM, CNKI, VIP, and WanFang.Papers were screened according to the inclusion and exclusion criteria, and then the data were extracted.Meta analysis was conducted using Stata 12.0 software.
Results
A total of 17 randomized controlled trials and a total of 1 151 patients were included in this study.Meta analysis showed that the short-term effect of experimental group was generally higher than that of control group (RR=1.51, 95%CI: 1.30-1.76, P<0.001). Subgroup analysis showed that Kanglaite combined with GP or PVM could significantly improve the short-time effect (P=0.026, 0.027 respectively). The improvement of KPS grade of experimental group was generally higher than that of control group (RR=1.51, 95%CI: 1.37-1.66, P<0.001). Subgroup analysis showed that Kanglaite combined with NP or CAP could significantly improve KPS grade (all P=0.000). The morbidity of nausea and vomiting of experimental group was generally lower than that of control group (RR=0.53, 95%CI: 0.44-0.64, P<0.001). Subgroup analysis showed that Kanglaite combined with GP or NP could significantly decrease the morbidity of nausea and vomiting (P=0.010, 0.004 respectively).
Conclusions
For patients with advanced non-small cell lung cancer, Kanglaite combined with chemotherapy can improve the short-time effect, the quality of life, and decrease the occurrence of adverse reaction.
Key words:
Non-small cell lung cancer; Kanglaite combined with chemotherapy; Chemotherapy; Meta analysis
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