Umbilical cord-derived mesenchymal stem (stromal) cells for treatment of severe sepsis: aphase 1 clinical trial

Xiao, He; Ai, Shanmu; Guo, Wei; Yang, Yi; Wang, Zhengguo; Jiang, Dongpo; Xu, Xiang

doi:10.1016/j.trsl.2018.04.006

Cited by 59 publications

(62 citation statements)

References 33 publications

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“…A variety of studies on hUC-MSC clinical trials performed a dose-escalation of hUC-MSCs of 0.5-5 million cells/kg in adults through intravenous infusions; the largest dose of a few trials reached 10 million cells/kg [27,28,36,37]. However, few trial reports explored the effect of different doses of hUC-MSCs in children's diseases, especially in those with severe BPD.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic human umbilical cord-derived mesenchymal stem cells for severe bronchopulmonary dysplasia in children: study protocol for a randomized controlled trial (MSC-BPD trial)

Xia

et al. 2020

Trials

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Background: Bronchopulmonary dysplasia (BPD) is a complex lung pathological lesion secondary to multiple factors and one of the most common chronic lung diseases. It has a poor prognosis, especially in preterm infants. However, effective therapies for this disease are lacking. Stem-cell therapy is a promising way to improve lung injury and abnormal alveolarization, and the human umbilical cord (hUC) is a good source of mesenchymal stem cells (MSCs), which have demonstrated efficacy in other diseases. We hypothesized that intravenously administered allogeneic hUC-MSCs are safe and effective for severe BPD. Methods: The MSC-BPD trial is a randomized, single-center, open-label, dose-escalation, phase-II trial designed to investigate the safety and efficacy of hUC-MSCs in children with severe BPD. In this study, 72 patients will be enrolled and randomly divided into two intervention groups and one control group. Patients in the intervention groups will receive a low dose of hUC-MSCs (n = 24; 2.5 million cells/kg) or a high dose of hUC-MSCs (n = 24; 5 million cells/kg) in combination with traditional supportive treatments for BPD. The patients in the control group (n = 24) will be treated with traditional supportive treatments alone without hUC-MSCs. The primary outcome measures will be cumulative duration of oxygen therapy. Follow-up assessments will be performed at 1, 3, 6, 12, and 24 months post intervention, and the key outcome during follow-up will be changes on chest radiography. Statistical analyses will evaluate the efficacy of the hUC-MSC treatment. Discussion: This will be the first randomized controlled trial to evaluate the safety and efficacy of intravenously administered hUC-MSCs in children with severe BPD. Its results should provide a new evidence-based therapy for severe BPD.

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Section: Discussionmentioning

confidence: 99%

Allogeneic human umbilical cord-derived mesenchymal stem cells for severe bronchopulmonary dysplasia in children: study protocol for a randomized controlled trial (MSC-BPD trial)

Xia

et al. 2020

Trials

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“…The updated meta-analysis presented here includes another seven high-quality studies [27,36,37,[39][40][41][42] that were mainly published in the last three years, and confirms the potential therapeutic efficacy of MSCs for reducing the mortality rate of sepsis in animal models, thus, providing possibilities for MSC therapy in preclinical studies of sepsis. To our knowledge, two small clinical phase 1 trials [43,44] have been performed to evaluate the safety and feasibility of MSC therapy in sepsis and septic shock patients.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, it is hard to comment on the clinical safety of MSC treatment. While immunogenicity is unrelated to MSC therapy [43,44], other significant risks still exist. Previous metaanalyses have shown no direct relationship between MSC administration and acute poisoning, systemic failure, malignancy, or death [50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of mesenchymal stem cell therapy for sepsis: A meta-analysis of preclinical studies

Ding

Liang

Zhang

et al. 2020

Preprint

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Background: Multiple studies have reported that mesenchymal stem cell (MSC) therapy has beneficial effects in experimental models of sepsis. However, this finding remains inconclusive. This study was performed to systematically determine the connection between MSC therapy and mortality in sepsis animal models by pooling and analyzing data from newly published studies.Methods: A detailed search of related studies from 2009 to 2019 was conducted in four databases, including MEDLINE, EMBASE, Cochrane Library, and Web of Science. After browsing and filtering out articles that met the inclusion criteria for statistical analysis, the inverse variance method of the fixed effects model was used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs).Results: Twenty-nine animal studies, including 1,266 animals, were identified. None of the studies were judged to have a low risk of bias. The meta-analysis demonstrated that MSC therapy was related to a significantly lower mortality rate (OR 0.29, 95% CI 0.22–0.38, P<0.001). Subgroup analyses performed based on the MSC injection dose (<1.0 × 106 cells, OR=0.33, 95% CI 0.20–0.56, P<0.001; 1.0 × 106 cells, OR=0.24, 95% CI 0.16–0.35, P<0.001) and injection time (<1 hour, OR=0.24, 95% CI 0.13–0.45, P<0.001; 1 hour, OR=0.28, 95% CI 0.17–0.46, P<0.001) demonstrated that treatment with MSCs significantly reduced the mortality rate of animals with sepsis.Conclusion: This up-to-date meta-analysis showed a connection between MSC therapy and lower mortality in sepsis animal models, supporting the potential therapeutic effect of MSC treatment in future clinical trials. The results in this study contradict a previous meta-analysis with regards to the ideal dose of MSC therapy. Thus, further research is required to support these findings.

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“…To date, a variety of studies on hUC-MSCs clinical trials have performed a dose-escalation of hUC-MSCs range from 0.5 million cells/kg to 5 million cells/kg in adult through intravenous infusion, and the largest dose of a few trials had reached 10 million cells/kg [28,29,36,37]. However, there are still few trial reports exploring the effect of different doses of hUC-MSCs in children's diseases, especially in severe BPD patients.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic human umbilical cord-derived mesenchymal stem cells for severe bronchopulmonary dysplasia in children: study protocol for a randomized controlled trial(the MSC-BPD Trial)

Xia

et al. 2019

Preprint

View full text Add to dashboard Cite

Background : Bronchopulmonary dysplasia (BPD) is a complex lung pathological lesion secondary to multiple factors, and one of the most common chronic lung diseases with poor prognosis, especially in preterm infants with severe BPD. However, there is lack of effective therapies for this disease. Stem cell therapy has been shown a promising way for improving lung injury and abnormal alveolarization, and human umbilical cord (hUC) is a good resource for mesenchymal stem cells (MSCs), which have demonstrated in some other diseases. We hypothesis that intravenous allogeneic hUC-MSCs is safe and effective for severe BPD. Methods/design: The MSC-BPD trial is a randomized single-center open-label and dose-escalation phase II trial designed to investigate the safety and efficacy of hUC-MSCs in children with severe BPD. In this study, 48 patients will be enrolled and randomly divided into two intervention groups and one control group. Patients in the intervention groups will be receive a low dose of hUC-MSCs (n=16, 2.5 million cells/kg) or a high dose of hUC-MSCs (n=16, 5 million cells/kg) in combination with traditional supportive treatments for BPD. The patients in the control group (n=16) will be treated with traditional supportive treatments alone without receiving hUC-MSCs treatment. The primary outcome measures will be the cumulative duration of oxygen therapy. Follow-up assessments will be performed at 1, 3, 6, 12, 24 months after interventions, and the key outcome during follow-up will be the chest radiography changes. Statistical analyses will evaluate the efficacy of the hUC-MScs treatment. Discussion: This study will be the first randomized controlled trial to evaluate the safety and efficacy of intravenous hUC-MSCs in children with severe BPD. Results of the trial will provide a new evidence-based therapy for severe BPD. Trial registration: ClinicalTrials.gov, NCT03601416. Registered on 26th July 2018. Key words: bronchopulmonary dysplasia, human umbilical cord-derived mesenchymal stem cells, clinical trial, protocol.

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Umbilical cord-derived mesenchymal stem (stromal) cells for treatment of severe sepsis: aphase 1 clinical trial

Cited by 59 publications

References 33 publications

Allogeneic human umbilical cord-derived mesenchymal stem cells for severe bronchopulmonary dysplasia in children: study protocol for a randomized controlled trial (MSC-BPD trial)

Allogeneic human umbilical cord-derived mesenchymal stem cells for severe bronchopulmonary dysplasia in children: study protocol for a randomized controlled trial (MSC-BPD trial)

Efficacy of mesenchymal stem cell therapy for sepsis: A meta-analysis of preclinical studies

Allogeneic human umbilical cord-derived mesenchymal stem cells for severe bronchopulmonary dysplasia in children: study protocol for a randomized controlled trial(the MSC-BPD Trial)

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