scholarly journals Induction Therapy With Mesenchymal Stem Cells in Kidney Transplantation: A Meta-Analysis

2020 ◽  
Author(s):  
Lingfei Zhao ◽  
Chenxia Hu ◽  
Fei Han ◽  
Dajin Chen ◽  
Jun Cheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Kidney Transplantation ◽  
Opportunistic Infection ◽  
Infection Rate ◽  
Induction Therapy ◽  
Meta Analysis ◽  
Graft Function ◽  
Renal Graft ◽  
Post Surgery

Abstract Objective The aim of this meta-analysis was to evaluate the therapeutic effects of mesenchymal stem cells (MSCs) versus other regimens as induction therapy in kidney transplantation patients.Methods PubMed, Embase, EBSCO, Ovid and the Cochrane Library were searched to identify prospective clinical trials which compared MSCs with other regimens as induction therapy in renal allograft.Results Four studies with five cohorts were contained, including a total of 301 patients. The pooled results revealed that the MSCs therapy had a lower 1-year infection rate (RR=0.73, 95% CI: 0.58–0.93, P=0.01), espeicially for 1-year opportunistic infection rate (RR=0.59, 95% CI: 0.37–0.93, P=0.02). There were no significant differences between the two protocols regarding 1-year acute rejection (AR) rate (RR=0.69, 95% CI: 0.42–1.14, P=0.15), 1-year graft survival rate (RR=0.99, 95% CI: 0.95–1.03, P=0.74), delayed graft function (DGF) rate (RR=0.72, 95% CI: 0.34–1.50, P=0.38) and renal graft function at 1 month (MD=2.4, 95% CI: -7.41– 12.22, p=0.63), 3 months (MD=0.91, 95% CI: -4.17– 5.98, p=0.73), 6 months (MD=-1.41, 95% CI: -5.69– 2.87, p=0.52), 12 months (MD=1.25, 95% CI: -3.89– 6.4, p=0.63) post surgery. Subgroup analysis demonstrated 1-year AR rate, DGF rate and renal graft function at 12 month post surgery did not reach to a significant difference between low-dose calcineurin inhibitors (CNIs) group with standard-dose CNIs group, indicating successful CNIs withdrawal in combination with MSCs treatment. Meanwhile, when applied MSCs as an alternative standard induction therapy regimen, all of those outcomes mentioned above were also comparable with those in MSCs plus standard induction therapy group.Conclusion Induction therapy of MSCs has similar inducing immune tolerance effects on the recipients in kidney transplantation compared with that of other regimens. However, regarding the long term effect, as represented by 1-year infection rate, 1-year opportunistic infection rate and CNIs withdrawl, MSCs therapy has a significant advantage.

scholarly journals Induction therapy with mesenchymal stromal cells in kidney transplantation: A meta-analysis

2020 ◽  
Author(s):  
Lingfei Zhao ◽  
Chenxia Hu ◽  
Fei Han ◽  
Dajin Chen ◽  
Jun Cheng ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Survival Rate ◽  
Graft Survival ◽  
Infection Rate ◽  
Mesenchymal Stromal Cells ◽  
Induction Therapy ◽  
Stromal Cells ◽  
Meta Analysis ◽  
Graft Function ◽  
Renal Graft

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 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 RCTs with large sample sizes and long follow-up periods.

scholarly journals Induction therapy with mesenchymal stromal cells in kidney transplantation: a meta-analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lingfei Zhao ◽  
Chenxia Hu ◽  
Fei Han ◽  
Dajin Chen ◽  
Jun Cheng ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Survival Rate ◽  
Graft Survival ◽  
Infection Rate ◽  
Mesenchymal Stromal Cells ◽  
Induction Therapy ◽  
Stromal Cells ◽  
Meta Analysis ◽  
Graft Function ◽  
Renal Graft

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.

scholarly journals Induction therapy with mesenchymal stromal cells in kidney transplantation: A meta-analysis

2020 ◽  
Author(s):  
Lingfei Zhao ◽  
Chenxia Hu ◽  
Fei Han ◽  
Dajin Chen ◽  
Jun Cheng ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Survival Rate ◽  
Graft Survival ◽  
Infection Rate ◽  
Mesenchymal Stromal Cells ◽  
Induction Therapy ◽  
Stromal Cells ◽  
Meta Analysis ◽  
Graft Function ◽  
Renal Graft

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 RCTs with large sample sizes and long follow-up periods.

scholarly journals Induction therapy with mesenchymal stromal cells in kidney transplantation: A meta-analysis

2021 ◽  
Author(s):  
Lingfei Zhao ◽  
Chenxia Hu ◽  
Fei Han ◽  
Dajin Chen ◽  
Jun Cheng ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Survival Rate ◽  
Graft Survival ◽  
Infection Rate ◽  
Mesenchymal Stromal Cells ◽  
Induction Therapy ◽  
Stromal Cells ◽  
Meta Analysis ◽  
Graft Function ◽  
Renal Graft

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 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 RCTs with large sample sizes and long follow-up periods.

Therapeutic Effect of Mesenchymal Stem Cells on Sjögren's Syndrome: Systematic Review and a Preclinical Meta-Analysis

2021 ◽  
Author(s):  
Yan Liu ◽  
Yi Xiong Chen ◽  
Nancy Olsen ◽  
Wael Jarjour ◽  
Yan Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Meta Analysis ◽  
Treatment Strategies ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Therapeutic Effects ◽  
Sjögren‘S Syndrome

Abstract BackgroundEvidence to support Mesenchymal stem cells (MSCs) treatment in Sjögren's syndrome (SS) has been verified. This study aims to evaluate the effectiveness of heterogeneous MSCs therapies, identify optimal experimental parameters and explore possible underlying mechanisms in animal models of SS.MethodsLiterature searches were performed in PubMed, Web of Science and EMBASE. Effect sizes of SS treatments with MSCs were extracted and analyzed by two authors independently.ResultsA total of 13 studies and 20 treatment arms met the inclusion criteria. When compared with the controls, MSCs treatment resulted in lower level of histological score (SMD= -2.208; 95%CI= -3.129, -1.286; P<0.001) accompanied by an improved trend of salivary flow rate (SFR) (SMD = 1.726; 95%CI= 1.340, 2.113; P <0.001) and Schirmer's test results (SMD= 3.379; 95% CI= 2.141, 4.618; P<0.001). In MSCs groups, levels of autoantibodies decreased to varying degrees. Treg cells were increased and Th17 cells were decreased in both lymph nodes and spleens. Additionally, IL-6 reduction and IL-10 elevation were found in local lesional tissues. Furthermore, TNF-α level dropped either in sera or glands. Notably, the cell injection frequency and routes may be two important factors affecting the effect of MSCs therapy.ConclusionTo the best of our knowledge, this is the first meta-analysis to quantitatively evaluate MSCs therapeutic effects on SS. Our research emphasizes optimizing MSC treatment strategies to achieve better outcomes, thereby providing a valuable reference for clinical application.

Mesenchymal stem cells immortalization's and state-of-art: a systematic review and meta-analysis

2021 ◽  
Vol 31 (Supplement_2) ◽  
Author(s):  
P E F Stricker ◽  
A C Irioda ◽  
B F Mogharbel ◽  
E Abdelwaid ◽  
L R Cavalli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Transfection ◽  
Meta Analysis ◽  
Total N ◽  
Htert Gene ◽  
Cell Immortalization ◽  
Immortalized Cell ◽  
Experimental Strategies ◽  
Established Technique

Abstract Background The immortalization of mesenchymal stem cells (MSCs) allows them to avoid senescence and be cultured through limitless cell passages. Thus, several experimental strategies, such as retrovirus-mediated gene transfer or viral oncogenesis, have been applied for the immortalization of MSCs. The aim was to identifier the most commonly used methodologies and their particularities for the immortalization of human and animal MSCs. Methods The search was conducted in June 2019 and developed in SCOPUS, PUBMED, and SCIENCE DIRECT. Statistical analysis was performed, obtaining the values of total n, mean and standard deviation, confidence interval (CI), and percentage (frequency) for all the predictors. Results The most used immortalization methodology was viral transfection, being the most common immortalized cell type was the bone marrow-derived MSC, and the most used gene for immortalizing both human and animal MSCs was hTERT (39.3%) and SV40T (54.5%). Among the articles analyzed in this review, only 39.3% and 36.4% of human and animal MSCs immortalization protocols, respectively, underwent the tumorigenicity test. Conclusions The virus-mediated gene transfection was observed as the most used and established technique. The insertion of the hTERT gene is still the most used gene for cell immortalization, suggesting that the maintenance of telomerase is efficient for maintaining cell proliferation and bypassing cell senescence. The review concluded that the tumorigenicity tests should become mandatory in order to safely use the immortalized MSCs for translation.

scholarly journals Clinical efficacy on glycemic control and safety of mesenchymal stem cells in patients with diabetes mellitus: Systematic review and meta-analysis of RCT data

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247662
Author(s):  
Jingjing He ◽  
Desheng Kong ◽  
Zhifen Yang ◽  
Ruiyun Guo ◽  
Asiamah Ernest Amponsah ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Random Effects ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
Significant Difference

Background Diabetes mellitus as a chronic metabolic disease is threatening human health seriously. Although numerous clinical trials have been registered for the treatment of diabetes with stem cells, no articles have been published to summarize the efficacy and safety of mesenchymal stem cells (MSCs) in randomized controlled trials (RCTs). Methods and findings The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to provide a reliable numerical summary and the most comprehensive assessment of therapeutic efficacy and safety with MSCs in diabetes. PubMed, Web of Science, Ovid, the Cochrane Library and CNKI were searched. The retrieval time was from establishment of these databases to January 4, 2020. Seven RCTs were eligible for analysis, including 413 participants. Meta-analysis results showed that there were no significant differences in the reduction of fasting plasma glucose (FPG) compared to the baseline [mean difference (MD) = -1.05, 95% confidence interval (CI) (-2.26,0.16), P<0.01, I2 = 94%] and the control group [MD = -0.62, 95%CI (-1.46,0.23), P<0.01, I2 = 87%]. The MSCs treatment group showed a significant decrease in hemoglobin (Hb) A1c [random-effects, MD = -1.32, 95%CI (-2.06, -0.57), P<0.01, I2 = 90%] after treatment. Additionally, HbA1c reduced more significantly in MSC treatment group than in control group [random-effects, MD = -0.87, 95%CI (-1.53, -0.22), P<0.01, I2 = 82%] at the end of follow-up. However, as for fasting C-peptide levels, the estimated pooled MD showed that there was no significant increase [MD = -0.07, 95%CI (-0.30, 0.16), P<0.01, I2 = 94%] in MSCs treatment group compared with that in control group. Notably, there was no significant difference in the incidence of adverse events between MSCs treatment group and control group [relative risk (RR) = 0.98, 95%CI (0.72, 1.32), P = 0.02, I2 = 70%]. The most commonly observed adverse reaction in the MSC treatment group was hypoglycemia (29.95%). Conclusions This meta-analysis revealed MSCs therapy may be an effective and safe intervention in subjects with diabetes. However, due to the limited studies, a number of high-quality as well as large-scale RCTs should be performed to confirm these conclusions.

scholarly journals Attenuation of Trauma-induced Osteoarthritis by Repetitive Intra-articular Administration of Peripheral Blood Derived Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Weiping Lin ◽  
Zhengmeng Yang ◽  
Liu Shi ◽  
Haixing Wang ◽  
Qi Pan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Subchondral Bone ◽  
Peripheral Blood ◽  
Cartilage Degradation ◽  
Cartilage Tissue ◽  
Synovial Joint ◽  
Post Surgery ◽  
Sham Surgery

Abstract Background: Osteoarthritis (OA) is a chronic joint disease, characterized by articular cartilage degradation, subchondral bone hardening, and inflammation of the whole synovial joint. There is no pharmacological treatment in slowing down OA progression, leading to costly surgical interventions eventually. Cell therapy using chondrocytes or progenitor cells from different sources has been reported in clinical trials for OA management with some success, but outcomes are varied. Peripheral blood derived mesenchymal stem cells (PB-MSCs) are promising cells owing to their easy collection, superior migration, and differentiation potentials. In the current study, we evaluated the effect of intra-articular administration of PB-MSCs on the progression of OA in mice.Methods: C57BL/6J mice (8-10 weeks old male) were subjected to destabilization of the medial meniscus surgeries (DMM) on their right joints following protocols as previously reported. The mice after DMM were randomly treated with saline (vehicle control), PB-MSCs, or adipose tissue derived MSCs (AD-MSCs) (n = 7 per group). The mice treated with sham surgery were regarded as sham controls (n = 7). PB-MSCs and AD-MSCs were harvested and cultured according to previous published protocols, and pre-labeled with BrdU for 48 h before use. PB-MSCs or AD-MSCs (5 × 105 cells/mouse; passage 3~5) were injected into the right knee joints thrice post-surgery (except sham surgery group). The mice were euthanized at 8 weeks post-surgery and knee joint samples were collected for micro-CT and histological examinations.Results: PB-MSCs administration significantly reduced hardening of subchondral bone comparing to vehicle controls. Safranin O staining showed that PB-MSCs treatment ameliorated degeneration of articular cartilage, which is comparable to AD-MSCs treatment. The expression of catabolic marker MMP13 was significantly reduced in articular cartilage of PB-MSCs-treated groups comparing to vehicle controls. Co-expression of BrdU and Sox9 were detected, indicating injected PB-MSCs differentiated towards chondrocytes in situ. Reduced level of IL-6 in the peripheral sera of PB-MSCs- and AD-MSCs-treated mice was also determined. Conclusions: Repetitive administration of PB-MSCs or AD-MSCs halted OA progression through inhibiting cartilage degradation and inflammation. PB-MSCs may become a promising cell source for cartilage tissue repair and alleviation of OA progression.

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