Safety Of Mesenchymal Stem Cells Research Articles

Meta-analysis shows that mesenchymal stem cell therapy can be a possible treatment for diabetes.

This meta-analysis includes the systematic literature review and meta-analysis involving clinical trials to assess the efficacy and safety of mesenchymal stem cell (MSC) transplantation for treating T1DM and T2DM. We searched PubMed, ScienceDirect, Web of Science, clinicaltrials.gov, and Cochrane Library for "published" research from their inception until November 2023. Two researchers independently reviewed the studies' inclusion and exclusion criteria. Our meta-analysis included 13 studies on MSC treatment for diabetes. The MSC-treated group had a significantly lower HbA1c at the last follow-up compared to the baseline (MD: 0.95, 95% CI: 0.33 to 1.57, P-value: 0.003< 0.05), their insulin requirement was significantly lower (MD: 0.19, 95% CI: 0.07 to 0.31, P-value: 0.002< 0.05), the level of FBG with MSC transplantation significantly dropped compared to baseline (MD: 1.78, 95% CI: -1.02 to 4.58, P-value: 0.212), the FPG level of the MSC-treated group was significantly lower (MD: -0.77, 95% CI: -2.36 to 0.81, P-value: 0.339 > 0.05), and the fasting C-peptide level of the MSC-treated group was slightly high (MD: -0.02, 95% CI: -0.07 to 0.02, P-value: 0.231 > 0.05). The transplantation of MSCs has been found to positively impact both types of diabetes mellitus without signs of apparent adverse effects.

Efficacy and safety of mesenchymal stem cell therapy for ovarian ageing in a mouse model

BackgroundOvarian ageing is one of the major issues that impacts female fertility. Mesenchymal stem cell (MSC)-based therapy has made impressive progress in recent years. However, the efficacy and safety of MSCs, as nonautologous components, remain to be further verified.MethodsTwo common sources of MSCs, umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (AD-MSCs), were orthotopically transplanted into a mouse model of ovarian ageing to evaluate their therapeutic effects. The safety of the treatment was further evaluated, and RNA sequencing was performed to explore the underlying mechanisms involved.ResultsAfter orthotopic transplantation of MSCs into the ovary, the oestrous cycle, ovarian weight, number and proportion of primary follicles, granulosa cell proliferation, and angiogenesis were improved. The effects of AD-MSCs were superior to those of UC-MSCs in several indices, such as post-transplant granulosa cell proliferation, ovarian weight and angiogenesis. Moreover, the tumorigenesis, acute toxicity, immunogenicity and biodistribution of MSCs were evaluated, and both AD-MSCs and UC-MSCs were found to possess high safety profiles. Through RNA sequencing analysis, enhancement of the MAPK cascade was observed, and long-term effects were mainly linked to the activation of immune function.ConclusionsOrthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice.

Efficacy and safety of mesenchymal stem cells in patients with acute ischemic stroke: a meta-analysis

ObjectiveThis meta-analysis and systematic review were conducted to comprehensively evaluate the efficacy and safety of mesenchymal stem cells in patients with acute ischemic stroke.MethodWe conducted a manual search of electronic databases, including PubMed, Embase, the Cochrane Library, and Web of Science, with a search deadline set for February 1, 2023. Data analysis was performed using Stata version 15.0.ResultA total of 9 randomized controlled studies were included, involving a total of 316 people, including 159 mesenchymal stem cells and 147 control groups. Results of meta-analysis: Compared to a placebo group, the administration of mesenchymal stem cells resulted in a significant reduction in the National Institutes of Health Stroke Scale (NIHSS) scores among patients diagnosed with acute ischemic stroke [SMD=-0.99,95% CI (-1.93, -0.05)]. Compared to placebo, barthel index [SMD = 0.48,95% CI (-0.55,1.51)], modified rankin score [SMD = 0.45, 95% CI (1.11, 0.21)], adverse events (RR = 0.68, 95% CI (0.40, 1.17)] the difference was not statistically significant.ConclusionBased on current studies, mesenchymal stem cell transplantation can ameliorate neurological deficits in patients with ischemic stroke to a certain extent without increasing adverse reactions. However, there was no significant effect on Barthel index and Modified Rankin score.

Analysis of efficacy and safety of mesenchymal stem cell and hematopoietic stem cell transplantation in rheumatoid arthritis: a systematic review and meta analysis of trials

Analysis of efficacy and safety of mesenchymal stem cell and hematopoietic stem cell transplantation in rheumatoid arthritis: a systematic review and meta analysis of trials

Efficacy and safety of mesenchymal and haematopoietic stem cells in secondary progressive multiple sclerosis: a systematic review and meta-analysis

Abstract Introduction Multiple sclerosis (MS) is a devastating, immune-mediated disease of the central nervous system (CNS)1. Despite extensive research, there is still no known definitive cure for MS1. Disease modifying therapies (DMTs) currently available are primarily approved for relapsing remitting multiple sclerosis (RRMS) and show limited evidence of efficacy in secondary progressive multiple sclerosis (SPMS). Moreover, DMTs do not halt disease progression or promote CNS repair2. In contrast, mesenchymal stem cells (MSCs) and haematopoietic stem cells (HSCs) have emerged as potential therapeutic approaches and have exhibited promising outcomes in MS clinical trials3. Aim The aim of this systematic review and meta-analysis was to assess the effectiveness and safety of MSCs and HSCs in the treatment of the SPMS sub-type. Methods A systematic search of PubMed, Web of Science, and Cochrane Library databases was conducted to identify eligible studies published from 1971 to 2022. Included studies focused specifically on SPMS and investigated MSC or HSC therapies. The systematic search identified 854 studies, following screening, fifteen studies (systematic review n = 15, meta-analysis n = 14) met the inclusion criteria, comprising 8 MSC studies and 7 HSC studies. The primary outcome measure was the expanded disability status scale (EDSS). Ethics approval was not deemed necessary for this research, as it falls within the scope of systematic reviews and meta-analyses. Results The study revealed a significant difference between baseline and final follow-up disability scores (EDSS) in the included studies [random-effects, MD = -0.17, 95%CI (-0.28, -0.06), P = 0.002, I2 = 29%]. The experimental groups showed a significant improvement in EDSS scores compared to the control group [random-effects, MD = -0.38, 95%CI (-0.66, -0.09), P = 0.01, I2 = 59%]. No statistically significant difference in efficacy was observed between MSCs and HSCs (unequal variance t-test, P = 0.73). Moderate adverse events were predominantly associated with MSC studies, while HSC studies reported more hospitalizations and three deaths. Discussion/Conclusion MSC and HSC transplantation demonstrated efficacy in improving the clinical course of SPMS. MSCs were found to have a moderate safety profile, while HSCs raised concerns due to the higher incidence of hospitalizations and fatalities. Additional investigations are necessary to further consolidate and establish the safety profile of HSCs. Despite the positive outcomes observed in the clinical trials, larger and more rigorous randomized controlled trials (RCTs) are needed to draw definitive conclusions regarding the therapeutic efficacy of these therapies. The limited number of RCTs represents a significant limitation of this study.

Umbilical Cord-Derived Mesenchymal Stem Cells Attenuate S100-Induced Autoimmune Hepatitis via Modulating Th1 and Th17 Cell Responses in Mice.

Currently, the first-line treatment for autoimmune hepatitis (AIH) is still the combination of glucocorticoids or immunosuppressants. However, hormone and immunosuppressive therapy can cause serious side effects, such as Cushing syndrome and bone marrow suppression. Previous studies reported on the applicability and safety of mesenchymal stem cells (MSCs) to ameliorate liver inflammation and fibrosis. However, the characteristics of MSCs sources directly contribute to the different conclusions on the mechanisms underlying MSC-mediated immunoregulation. Bone marrow-derived MSCs can exert an immunosuppression effect to ameliorate the S100-induced AIH model by inhibiting several proinflammatory cytokines and upregulating of PD-L1 in liver tissue. It is not clear whether human umbilical cord-derived MSCs (hUC-MSCs) could directly inhibit liver inflammation and ultimately alleviate the dysfunction of hepatocytes in the AIH model. First, hUC-MSCs were extracted from umbilical cord tissue, and the basic biological properties and multilineage differentiation potential were examined. Second, 1 × 106 hUC-MSCs were administered intravenously to AIH mice. At the peak of the disease, serum levels of alanine aminotransferase and aspartate aminotransferase and pathologic damage to liver tissue were measured to evaluate liver function and degree of inflammation. We also observed that the infiltration of CD4+ T cells in the liver was significantly reduced. Furthermore, the frequency of the splenic IFNγ- and IL-17A- producing CD4+ T cells were also significantly decreased, while we only observed an increasing trend in Treg cells in liver tissue. Third, an RNA sequencing analysis of liver tissue was performed, which showed that in the UC-MSC-treated group, the transcriptional profiles of inflammation-related signaling pathways were significantly negatively regulated compared to those of phosphate-buffered saline-treated mice. Collectively, these findings indicated the potential of hUC-MSC to suppress immune responses in immune anomaly mediated liver disease, thus offering a potential clinical option to improve AIH.

Mesenchymal Stem Cells in the Treatment of COVID-19.

Since the emergence of the coronavirus disease 2019 (COVID-19) pandemic, many lives have been tragically lost to severe infections. The COVID-19 impact extends beyond the respiratory system, affecting various organs and functions. In severe cases, it can progress to acute respiratory distress syndrome (ARDS) and multi-organ failure, often fueled by an excessive immune response known as a cytokine storm. Mesenchymal stem cells (MSCs) have considerable potential because they can mitigate inflammation, modulate immune responses, and promote tissue regeneration. Accumulating evidence underscores the efficacy and safety of MSCs in treating severe COVID-19 and ARDS. Nonetheless, critical aspects, such as optimal routes of MSC administration, appropriate dosage, treatment intervals, management of extrapulmonary complications, and potential pediatric applications, warrant further exploration. These research avenues hold promise for enriching our understanding and refining the application of MSCs in confronting the multifaceted challenges posed by COVID-19.

Effect and safety of mesenchymal stem cells for patients with COVID-19: Systematic review and meta-analysis with trial sequential analysis.

The objective of this study was to assess whether mesenchymal stem cells (MSCs) therapy could offer survival advantages for patients with novel coronavirus disease 2019 (COVID-19). An electronic search of PubMed, Embase, Cochrane Library, Web of Science, WanFang, and CNKI was performed from December 1, 2019 to December 25, 2022. The primary outcome was all-cause mortality. Trial sequential analysis (TSA) was conducted in this meta analysis. Besides, subgroup analysis and meta-regression was performed using a random-effects model to find the potential sources of heterogeneity. Seventeen randomized controlled trials (RCTs) involving a total of 1073 patients with COVID-19 were included in this study. Compared with the control group, patients in the MSCs groups were associated with significantly reduced all-cause mortality (MSCs 18.4% vs. control 25.5%; risk ratio [RR] 0.73; 95% confidence interval [CI] 0.59-0.90; p = 0.004; I² = 0%). For all secondary outcomes, there wasn't significant improvement in the experimental group versus the control group regarding symptom remission rate (53.2%, 201/378 vs. 46.5%, 164/353; RR 1.15; 95% CI 1.00-1.32; p = 0.05; I² = 43%), but the pooled analysis revealed significant differences between the groups in length of hospital stay(MD: -3.82, 95% CI: -5.87 to -1.77; p = 0.0003, I2 = 0%), requirement of invasive mechanical ventilation(RR 0.52; 95% CI 0.33-0.82; p = 0.005; I2 = 0%) and post-CRP level (MD: -31.61; 95% CI -46.74 to -16.49; p < 0.0001). Moreover, regarding the incidence of adverse events (AEs) (RR 0.73; 95% CI 0.35-1.52; p = 0.39; I² = 44%) and serious adverse events (sAEs) (RR 0.87; 95% CI 0.40-1.92; p = 0.73; I² = 39%), no significant differences were observed between MSCs and control groups. The TSA analysis showed that the result of all-cause mortality might be false-positive result. Based on the pooled results in this study, compared with standard treatment, MSCs therapy may reduce all-cause mortality of patients with COVID-19 with no increase risk of AEs and sAEs, but may not improve symptom remission rate. Further more high-quality and large-sample RCTs should be performed to confirm these findings.

Mesenchymal Stem Cells Versus Placebo for Perianal Fistulizing Crohn's Disease: A Systemic Review and Meta-Analysis.

Mesenchymal stem cells (MSCs)-based therapy for perianal fistulizing Crohn's disease (pfCD) has been extensively studies in the past decade. Its efficacy and safety had been preliminarily confirmed in some phase 2 or phase 3 clinical trials. This meta-analysis is performed to evaluate the efficacy and safety of MSCs-based therapy for pfCD. Electronic databases (Pubmed, Cochrane Library, Embase) were searched for studies that reported the efficacy and safety of MSCs. And RevMan were used to assess the efficacy and safety. After screening, 5 randomized controlled trials (RCTs) were included in this meta-analysis. RevMan 5.4 for meta-analysis showed that: [Efficacy] Patients had definite remission after MSCs treatment, with an odds ratio (OR) of 2.06 (P < .0001, 95%CI 1.46, 2.89) vs controls. [Safety] The incidence of the most frequently reported TEAEs (treatment-emergent adverse events, TEAEs), perianal abscess and proctalgia, did not significantly increase due to the use of MSCs, with an OR of 1.07 in perianal abscess (P = .87, 95%CI 0.67, 1.72) vs controls, and an OR of 1.10 in proctalgia (P = .47, 95%CI 0.63, 1.92) vs controls. MSCs seem to be an effective and safe therapy for pfCD. MSCs based therapy has the potential to be used in combination with traditional therapies.

Efficacy and Safety of Mesenchymal Stem Cells for COVID-19 Infection: A Meta-Analysis and Systematic Review.

COVID-19 (coronavirus disease 2019) is a pandemic around the world, and its treatment options often fail to achieve ideal results. There is a lot of controversy in the treatment of COVID-19 with mesenchymal stem cells (MSCs). The study aims to assess the safety and efficacy of mesenchymal treatment of new coronary pneumonia. We manually searched electronic databases including PubMed, Embase, Cochrane Library, and Web of Science until 25th July 2022, and Stata 15.0 (StataCorpLLC: College Station, TX, USA) was used to analyze the data. A total of 8 randomized controlled trials were included, involving a total of 345 people, of which 180 were in the MSCs group and 165 were in the placebo group. The analysis results showed that MSCs can reduce mortality in COVID-19 patients compared to placebo [RR (Risk Ratio) = 0.56, 95% CI (Confidence Interval) (0.36, 0.89); p = 0.003]. There was no significant difference between the mesenchymal stem cell group and the placebo group in the incidence of adverse reactions [RR = 0.64, 95% CI (0.34, 1.18); p = 0.281]; In the SpO2/FiO2 (Oxygen Saturation/Fraction of Inspiration O2) [WMD (Weighted Mean Difference) = 9.07, 95% CI (-38.01, 56.15); p = 0.080]; In ICU (Intensive Care Unit) stay [WMD = -1.66, 95% CI (-7.23, 3.91); p = 0.131]. Mesenchymal stem cells can reduce the mortality of COVID-19 patients.

Efficacy and safety of mesenchymal stem cells in the treatment of perianal fistulas in Crohn's disease: a meta-analysis of randomized controlled trials.

Local mesenchymal stem cell (MSC) therapy for perianal fistulas in Crohn's disease (CD) has yielded promising results, but it still remains controversial. In this study, we aimed to conduct a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of MSC therapy for perianal CD (pCD). RCTs reporting MSC therapy for perianal fistulas in CD were searched and included. The effectiveness and safety data were analyzed using RevMan 5.3. A total of 7 RCTs were included in this meta-analysis. The analysis showed that patients receiving MSC therapy presented a higher healing rate (HR) of pCD than those in the control group (odds ratio (OR)=1.42; 95% confidence interval (CI) 1.18, 1.71; P=0.0002). Compared with placebo (saline solution), MSC therapy improved the HR of pCD (OR=1.85; 95% CI 1.32, 2.60; P=0.0004). MSC therapy showed significant long-term efficacy (OR=1.36; P=0.009; 95% CI 1.08, 1.71). When MRI was used to evaluate fistula healing, a pooled analysis showed that the MSC group achieved a higher HR than the control group (OR=1.95; 95% CI 1.33, 2.87; P=0.0007). Allogeneic MSC therapy was superior to the control treatment in improving HR (OR = 1.97; 95% CI 1.40, 2.75; P<0.001). Furthermore, no significant differences were observed between MSC therapy and placebo in terms of adverse events (AEs) (OR = 1.16; 95% CI 0.76, 1.76; P = 0.48). None of the AEs were judged to be related to MSC treatment. This meta-analysis of RCTs provided evidence that local MSC injection is safe and efficacious for perianal fistulas in CD. In addition, this treatment has favorable long-term efficacy and safety profiles.

BDNF-overexpressing MSCs delivered by hydrogel in acute ischemic stroke treatment.

Ischemic stroke treatment is a challenge worldwide. The efficacy and safety of mesenchymal stem cells (MSCs) for stroke have been confirmed. However, poor survival of MSCs in the ischemic environment limits the therapy efficacy. Changes in MSC status in the ischemic environment after transplantation is difficult to monitor. This study aimed to deliver brain-derived neurotrophic factor (BDNF)-overexpressing MSCs by hydrogel (H-B-MSCs) to promote recovery after ischemic stroke. MSCs were transfected with lentivirus carrying luc2 and BDNF cassette. The properties of hydrogel were tested after synthesis with thiolated gelatin (Gel-SH), thiolated hyaluronic acid (HA-SH), and polyethylene glycol diacrylate (PEGDA). Oxygen-glucose deprivation (OGD) test was carried out to confirm the protective effects of hydrogel in the ischemic environment. Three days after stroke induction, H-B-MSCs, hydrogel carrying MSCs (H-MSCs), or phosphate-buffered saline (PBS) was injected into the brains of mice, respectively. Bioluminescence imaging (BLI) was performed at 3, 7, 14, and 21 days post-cell-transplantation to monitor the dynamic status of MSCs. In the meantime, histology, quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbentassay (ELISA), western blot, and behavior tests were carried out at different time points. Hydrogel with good biocompatibility was synthesized. Lentivirus transfection significantly increased the expression of BDNF. BDNF-MSCs could be tracked by BLI in vitro. In vitro OGD/reperfusion (OGD/R) test results suggested that MSCs carried by hydrogel could survive longer in an environment with low oxygen and glucose. H-B-MSCs significantly improved functional recovery after ischemic stroke. Furthermore, H-B-MSCs treatment promoted neurogenesis, white matter recovery, and angiogenesis after ischemic stroke. MSC dynamics could be monitored in vivo with BLI. We effectively established a robust MSC delivery system with hydrogel. Prolonged survival of transplanted BDNF-MSCs with a hydrogel delivery system could promote the recovery of ischemic stroke via the continuous release of BDNF.

Equine umbilical cord mesenchymal stem cells demonstrate safety and efficacy in the treatment of canine osteoarthritis: a randomized placebo-controlled trial.

To demonstrate the efficacy and safety of mesenchymal stem cells (MSCs) for xenogeneic use with intra-articular administration in dogs with osteoarthritis. 80 client-owned dogs with naturally occurring osteoarthritis in elbow or hip. A multicentric, double-blinded, parallel, randomized and placebo-controlled clinical trial was performed. After intra-articular injection of equine umbilical cord MSCs, dogs were reexamined at weeks 4, 8, and 12 using a force platform (gait analysis), orthopedic assessment, and validated owner questionnaire. Eighteen months after treatment, a long-term follow-up was done. Best results were obtained 8 weeks after treatment, where 63% of the patients showed an improvement in the gait analysis. Also 8 weeks after treatment, 77% of the dogs improved in the orthopedic examination; 65% of the owners considered that the treatment improved their pet's quality of life 8 weeks after treatment. The long-term follow-up revealed that 59% of the owners observed a duration of effect longer than 6 months after a single intra-articular injection of equine umbilical cord MSCs. No systemic or permanent adverse events were detected at any time point. Results of this study demonstrated the safety and efficacy of intra-articular administration of xenogeneic MSCs for the treatment of canine osteoarthritis.

Combination of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) in the treatment of knee osteoarthritis: a meta-analysis of randomised controlled trials

ObjectivesThe purpose of this meta-analysis was to investigate the efficacy and safety of mesenchymal stem cells (MSCs) combined with platelet-rich plasma (PRP) in the treatment of knee osteoarthritis (KOA).DesignSystematic review...

The Effectiveness and Safety of Mesenchymal Stem Cells in the Treatment of Osteoarthritis: A Systematic Review and Meta-analysis of 28 Randomized Controlled Trials.

Objective To evaluate the effectiveness and safety of mesenchymal stem cells (MSCs) in the treatment of osteoarthritis (OA). Methods Chinese databases (such as CNKI and SinoMed) and English databases (such as PubMed and Embase) were searched to collect randomized controlled trials (RCTs) of MSCs in the treatment of OA. The retrieval time is from inception to October 10, 2021. The literature was strictly selected according to the inclusion and exclusion criteria, data was extracted, and the quality was evaluated. RevMan 5.3 software was used for meta-analysis. STATA was used to evaluate publication bias. The registration number of this systematic review and meta-analysis is CRD42021277145. Results A total of 28 RCTs involving 1494 participants were included. The primary outcomes showed that MSCs may reduce WOMAC pain and VAS at the 3rd-month follow-up [WOMAC pain: -3.81 (-6.95, -0.68), P = 0.02. VAS: -1.11 (-1.53, -0.68), P < 0.00001], and the effect lasts for at least 12 months [WOMAC pain: -4.29 (-7.12, -1.47), P = 0.003. VAS: -1.77 (-2.43, -1.12), P < 0.00001]. MSCs may also reduce WOMAC stiffness and physical function at the 6th-month follow-up [WOMAC stiffness: -1.12 (-2.09, -0.14), P = 0.03. WOMAC physical function: -4.40 (-6.84, -1.96), P = 0.0004], and the effect lasts for at least 12 months [WOMAC stiffness: -0.99 (-1.95, -0.03), P = 0.04. WOMAC physical function: -3.26 (-5.91, -0.61), P = 0.02]. The improvement of WOMAC pain, VAS, WOMAC stiffness, and WOMAC physical function may be clinically significant. Meanwhile, after the MSC injection, Lequesne had been reduced compared with the control group [-4.49 (-8.21, -0.77), P = 0.002]. For adverse events, there is no significant difference in the safety of MSC injection and the control group [1.20 (0.97, 1.48), P = 0.09]. The quality of WOMAC physical function and adverse events were moderate. Conclusion Based on current evidence, MSCs may be a safety therapy that have a good curative effect in the treatment of OA, the onset time is no later than 3 months, and the time to maintain the curative effect is no less than 12 months. However, these results should be generalized with caution due to the generally low quality of evidence and RCTs.

Is mesenchymal stem cell effective for allergic rhinitis? A protocol for a systematic review and meta-analysis

IntroductionAllergic rhinitis (AR) is a kind of widespread but unrecognised inflammatory disorder of nasal mucosa, characterised by itching, sneezing, runny nose and nasal congestion. The efficacy of mesenchymal stem cells...

Mesenchymal stromal/stem cell therapy for radiation-induced salivary gland hypofunction in animal models: a protocol for a systematic review and meta-analysis

BackgroundSalivary gland (SG) hypofunction (objectively reduced saliva flow rate) and xerostomia (subjective sensation of dry mouth) are common and burdensome side effects of radiotherapy to the head and neck region. Currently, only sparse symptomatic treatment is available to ease the discomfort of xerostomia. The objective of this study is to assess the effect of mesenchymal stem cell (MSC) therapy on SG function after radiation-induced injury.MethodsThis systematic review will include animal intervention studies assessing efficacy and safety of MSCs in treating radiation-induced SG hypofunction. The primary outcome is the effect of MSC administration on salivary flow rates (SFR), by comparing treated groups to control groups when available. Secondary outcomes are morphological and immunohistochemical effects as well as safety of MSC treatment. Electronic searches in MEDLINE (PubMed) and Embase databases will be constructed and validated according to the peer review of electronic search strategies (PRESS) and assessed by two independent researchers. Data from eligible studies will be extracted, pooled, and analyzed using random-effects models. Risk of bias will be evaluated with the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool.DiscussionThus far, critical appraisal of MSC therapy as an effective treatment for SG hypofunction caused solely by radiation injury has not been conducted. A summary of the existing literature on preclinical studies concerning this issue can provide valuable information about effectiveness, mode of action, and safety, allowing further optimization of preclinical and clinical trials.Systematic review registrationPROSPERO CRD42021227336

Safety of DW-MSC infusion in patients with low clinical risk COVID-19 infection: a randomized, double-blind, placebo-controlled trial

BackgroundDue to their immunomodulatory properties, mesenchymal stem cells (MSCs) have been proposed to have therapeutic potential to improve clinical outcomes in COVID-19. However, the safety and efficacy profile of MSC infusion therapy in patients with non-severe COVID-19 infection has not been completely established; there is, in particular, a substantial void in the literature on dose-dependent studies of MSC infusion in patients with low clinical risk COVID-19 infection.MethodsThis phase 1 double-blind, placebo-controlled, randomized clinical trial examines the safety, feasibility, and tolerability of 2 doses (high and low) of DW-MSC in patients with low clinical risk COVID-19. A total of 9 patients were enrolled in this study and randomized into low-dose (TL), high-dose (TH), and placebo (C) groups. Subjects in the TL and TH groups received single intravenous infusions of 5.0 × 107 cells and 1.0 × 108 cells, respectively. The main outcome was the occurrence of treatment-emergent adverse events (TEAE) during the 28-day study period. Vital signs and various inflammatory markers were also monitored weekly during the observation period.ResultsThere were no apparent differences in clinical characteristics between study groups (TL, TH, and C) at baseline. All patients did not show the progression of severity during the study period. During the course of the study, 6 episodes of TEAE were observed in 5 subjects; however, none of the TEAEs were severe. During the follow-up period, 8 subjects recovered and were discharged from the hospital without complications. A subject exhibited abnormal liver function biomarkers at the end of the study period. Changes in inflammatory markers throughout the clinical course were not vastly different across study groups.ConclusionsOur clinical trial has provided reliable results regarding the safety of MSCs in low clinical risk COVID-19 subjects treated with MSCs. However, further confirmation of the therapeutic efficacy aspects of MSC will require large-scale randomized controlled trials in subjects with varying severity profiles for COVID-19.Trial registrationClinicalTrials.gov, NCT04535856. Registered 2 September 2020, https://clinicaltrials.gov/ct2/show/NCT04535856

Efficacy and Safety of Mesenchymal Stem Cell Transplantation in the Treatment of Autoimmune Diseases (Rheumatoid Arthritis, Systemic Lupus Erythematosus, Inflammatory Bowel Disease, Multiple Sclerosis, and Ankylosing Spondylitis): A Systematic Review and Meta-Analysis of Randomized Controlled Trial.

Objective To evaluate the efficacy and safety of mesenchymal stem cell (MSC) transplantation in the treatment of autoimmune diseases. Methods The Chinese and English databases were searched for clinical research on the treatment of autoimmune diseases with mesenchymal stem cells. The search time range is from a self-built database to October 1, 2021. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted data, and evaluated the bias of the included studies. RevMan 5.3 analysis software was used for meta-analysis. Results A total of 18 RCTs involving 5 autoimmune diseases were included. The 5 autoimmune disease were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease, ankylosing spondylitis, and multiple sclerosis. For RA, the current randomized controlled trials (RCTs) still believe that stem cell transplantation may reduce disease activity, improve the clinical symptoms (such as DAS28), and the percentage of CD4+CD 25+Foxp3+Tregs in the response group increased and the percentage of CD4+IL-17A+Th17 cells decreased. The total clinical effective rate of RA is 54%. For SLE, the results showed that mesenchymal stem cell transplantation may improve SLEDAI [-2.18 (-3.62, -0.75), P = 0.003], urine protein [-0.93 (-1.04, -0.81), P < 0.00001], and complement C3 [0.31 (0.19, 0.42), P < 0.00001]. For inflammatory bowel disease, the results showed that mesenchymal stem cell transplantation may improve clinical efficacy [2.50 (1.07, 5.84), P = 0.03]. For ankylosing spondylitis, MSC treatment for 6 months may increase the total effective rate; reduce erythrocyte sedimentation rate, intercellular adhesion molecules, and serum TNF-α; and improve pain and activity. For multiple sclerosis, the current research results are still controversial, so more RCTs are needed to amend or confirm the conclusions. No obvious adverse events of mesenchymal stem cell transplantation were found in all RCTs. Conclusion MSCs have a certain effect on different autoimmune diseases, but more RCTs are needed to further modify or confirm the conclusion.

Efficacy and safety of mesenchymal stem cells in the treatment of systemic sclerosis: a systematic review and meta-analysis

BackgroundSystemic sclerosis (SSc) is an autoimmune disease with high morbidity and mortality characterized by fibrosis of the skin and internal organs. Some studies have investigated the use of stem cells to treat SSc. Herein, a systematic review and meta-analysis was conducted to determine the efficacy and safety of mesenchymal stem cells (MSCs) in the treatment of SSc.MethodsPubMed, Embase, Cochrane Library, Web of Science, OVID, China National Knowledge Infrastructure and Wanfang databases were searched up to February 1, 2021. Literature screening, data extraction and quality assessment were conducted independently by two researchers in according to the inclusion and exclusion criteria. The discrepancies were resolved by a third researcher.ResultsA total of 9 studies encompassing 133 SSc patients were included in the study. Compared to the baseline after treatment with MSCs: 1. The modified Rodnan skin score (mRSS) was significantly reduced in patients with SSc (P < 0.00001). 2. MSCs decreased the number of digital ulcer, mouth handicap scale, and visual analog scale of hand pain in SSc patients (P = 0.0007 and P = 0.03, respectively). 3. No statistical differences were detected in Raynaud's condition score and Cochin hand function scale score at 6 months of MSCs therapy (P = 0.5 and P = 0.62). 4. After 12 months of follow-up, MSCs improve carbon monoxide diffusing capacity and forced vital capacity of SSc patients (P < 0.05). 5. Overall, MSCs application was safe; a few cases exhibited swelling at the injection site, diarrhea and arthralgia, which had self-recovery, and no severe adverse events occurred in the included trials.ConclusionsMSC therapy improves the degree of skin thickening, lung function, and mouth opening and relieves finger ulcers and pain in patients with SSc without severe adverse events. Thus, MSCs or MSCs combined with plasma and traditional medicine might be an effective and promising treatment of SSc patients.PROSPERO registration number: CRD42020200350