Dataset Information

Efficacy of umbilical cord mesenchymal stem cell transfusion for the treatment of severe AKI: a protocol for a randomised controlled trial.

ABSTRACT:

Introduction

Acute kidney injury (AKI) is a common and severe clinical problem that is associated with high mortality, a long hospital stays and high healthcare resource consumption. Approximately a quarter of AKI survivors will develop chronic kidney disease. Mesenchymal stem cells (MSCs) are multipotent stem cells with antiapoptotic, immunomodulatory, antioxidative and proangiogenic properties. Therefore, MSCs have been considered as a potential new therapy for the treatment of AKI. Several clinical trials have been performed, but the results have been inconsistent. This trial investigated whether MSCs can improve renal recovery and mortality in patients with severe AKI.

Methods and analysis

One hundred subjects suffering from severe AKI will participate in this patient-blinded, randomised, placebo-controlled, parallel design clinical trial. Participants will be randomly assigned to receive two doses of MSCs or placebo (saline) on days 0 and 7. Urinary biomarkers of renal injury and repair will be measured using commercially available ELISA kits. The main outcome measures are changes in renal function levels within the first 28 days following MSC infusion.

Ethics and dissemination

The study was approved by the Ethics Committee of the Chinese PLA General Hospital. The findings of the study will be disseminated through public and scientific channels.

Trial registration number

NCT04194671.

SUBMITTER: Yang Y

PROVIDER: S-EPMC8862499 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Efficacy of umbilical cord mesenchymal stem cell transfusion for the treatment of severe AKI: a protocol for a randomised controlled trial.

Yang Yuanjun Y Gao Jianjun J Wang Siyang S Wang Wenjuan W Zhu Fang-Lei FL Wang Xiaolong X Liang Shuang S Feng Zhe Z Lin Shupeng S Zhang Li L Chen Xiangmei X Cai Guangyan G

BMJ open 20220221 2

<h4>Introduction</h4>Acute kidney injury (AKI) is a common and severe clinical problem that is associated with high mortality, a long hospital stays and high healthcare resource consumption. Approximately a quarter of AKI survivors will develop chronic kidney disease. Mesenchymal stem cells (MSCs) are multipotent stem cells with antiapoptotic, immunomodulatory, antioxidative and proangiogenic properties. Therefore, MSCs have been considered as a potential new therapy for the treatment of AKI. Se ...[more]

PMID: 35190406

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Project description:BackgroundMesenchymal stem cells (MSCs) possess powerful immunomodulatory ability. This study aimed to assess the efficacy and safety of human umbilical cord-derived mesenchymal stem cells (UMSCs) in patients with ulcerative colitis (UC) and to explore the potential mechanisms.MethodsThis prospective, self-controlled clinical study was conducted at Henan Provincial People's Hospital. Patients with moderate-to-severe active UC, unresponsive to traditional drugs were continuously enrolled from September 2018 to March 2023. UMSCs were administered intravenously monthly for two months at a cell dosage of 1 × 106 per kg. The primary outcome was a clinical response at 2 months. The levels of cytokines and progerin in the plasma of the patients were analyzed using enzyme-linked immunosorbent assay kits, and longitudinal data was analyzed using generalized estimation equation.ResultsForty-one patients were enrolled and received UMSC therapy. At 2 months, 73.2% (30/41) of patients achieved a clinical response, and 41.5% (17/41) achieved a clinical remission. At 6 months, 2 patients were lost to follow-up; the corresponding figures were 70.0% (25/41) and 34.2% (14/41), respectively. After UMSC therapy, the Mayo score, Mayo endoscopy score, mean and maximum values of Ulcerative Colitis Endoscopic Index of Severity and Nancy index were significantly reduced compared with baseline values. Additionally, the levels of progerin and inflammatory markers, such as interleukin (IL)-1β, IL-6, IL-8, IL-12, and IL-17 A decreased, while hemoglobin, albumin, and IL-10/IL-17 A ratio increased, particularly in the response group. Multiple stepwise logistic regression analysis showed age was an independent risk factor affecting efficacy (odds ratio, 0.875 (95% confidence interval (0.787, 0.972)); the area under the receiver operating characteristic curve for age was 0.79. No serious adverse events were observed during or after UMSC therapy.ConclusionUMSCs are safe and effective for patients with UC, with age being an independent risk factor affecting efficacy. Mechanistically, UMSC treatment may ameliorate cell senescence and suppress the secretion of pro-inflammatory cytokines.Trial registrationThe study was retrospectively registered at www.chictr.org.cn/ (ChiCTR1900026035) on September 18, 2019.

Project description:ObjectiveThis study explored the underlying therapeutic mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) for ischemic stroke (IS), and determined the optimal administration time windows and dose-effect relationship.MethodsThe levels of SDF-1α, IL-10, IL-6, TNF-α, BDNF, IL-1β, and VEGF-A factors in serum and brain tissue lysate were measured by ELISA. The pathological status of brain tissues was evaluated by Hematoxylin-Eosin (HE) staining, and apoptosis of nerve cells was detected by tunel. The protein expression of CXCR-4, NeuN, and Nestin in the brain tissues was assessed through immunofluorescence. The balance beam, forelimb muscle strength, and limb placement were tested on MCAO rats at different time points and doses. The infarct area of the rat brain tissues was measured at the end of the experiment.ResultsThe hUCMSC treatment during the acute phase of MCAO significantly reduced the secretion of IL-6, TNF-α, IL-1β but increased IL-10 in serum, and the levels of SDF-α and BDNF in serum and brain tissues lysate were also increased. The pathological results showed that there were more neurons in the treatment group compared to the model group. Immunofluorescence assays showed that the expression of CXCR4、Nestin、NeuN was relatively higher than that in the model group. The d4 and d7 treatment significantly improves the motor function, promotes the recovery of forelimb muscle strength, increases the forelimb placement rate and reduces the scope of cerebral infarction, but the d14 treatment group has less therapeutic effect compared to the d4 and d7 treatment. The 2×107/kg treatment showed the best therapeutic effect, followed by the 1×107/kg treatment, and the worst is 0.5×107/kg treatment from the test of balance beam, forelimb muscle strength, limb placement and the infarct area of the rat brain tissues.ConclusionThe hUCMSCs can inhibit the infiltration of inflammatory cells in the brain tissue, and promote the repair of brain tissue structure and function. Early intervention by injecting high-dose of hUCMSCs can significantly improve the recovery of neurological/motor function and reduce the size of cerebral infarction in rats.

Project description:ObjectiveUmbilical cord mesenchymal stem cells (UCMSCs) have significant regenerative, tissue repair, and immunomodulatory properties that can help reduce inflammatory responses in patients with ankylosing spondylitis (AS). In this study, we used a combination of bovine proteoglycan and dimethyldioctadecylammonium (DDA) to establish a mouse model of proteoglycan-induced spondylitis (PGISp). To evaluate the therapeutic effects of UCMSCs, we treated PGISp mice with different doses of hUCMSCs via tail vein injection.MethodsAt week 13, the PGISp mice exhibited thickened, erythematous paws, erythema in the extremities, and lameness. CT scans revealed necrotic lysis of chondrocytes, formation of fissures, visible hemorrhage, connective tissue hyperplasia, and focal infiltration of lymphocytes in the intervertebral discs. At week 14, the PGISp mice were randomly divided into three groups and administered different doses of hUCMSCs (0.25, 0.5, and 1.0×107 cells/kg, iv, QOW×2, n=10). To assess the therapeutic effects of hUCMSCs, we evaluated Th cell subsets in the spleen, spleen and thymus coefficients, peripheral blood inflammatory factors, and pathological and imaging observations of the spines and lumbar spines in the PGISp mice.ResultsThe results demonstrated that injection of hUCMSCs shifted the balance axis between Th1 and Th2 cells in the spleen towards Th2 cells. Moreover, the spleen coefficient and levels of inflammatory cytokines (TNF-α and CCL-2) in the serum decreased after hUCMSC injection. CT imaging and pathological analysis indicated that hUCMSC treatment inhibited ectopic osteogenesis and maintained clear small joint gaps, which slowed down the progression of structural lesions in the disc, nucleus pulposus, fibrous ring, and cartilage in PGISp mice.ConclusionAdministering hUCMSCs at the 14th week after modeling proved to be an effective treatment for PGISp mice. This experiment offers a valuable reference for the pre-clinical use of hUCMSCs in the treatment of AS.

Project description:IntroductionSepsis is a life-threatening organ disorder caused by a dysregulated inflammatory response to infection with no effective treatment options exist thus far. Therefore, novel therapeutic methods are urgently advocated for decreasing the high mortality rate. Recently, preclinical studies supported the efficacy of mesenchymal stem cells (MSCs) in the treatment of sepsis. In this study, we aim to test the safety, tolerability and efficacy of human umbilical cord MSCs (HUC-MSCs) for the treatment of pneumonia induced sepsis.Methods and analysisThis study is a single-centre, randomised single-blind parallel group, placebo-controlled trial. Forty eligible participants with pneumonia-induced sepsis will be randomly assigned to the observational cohort and the interventional cohort in a 1:1 ratio. In addition to the standard treatments recommended by the Sepsis 3.0 guidelines, HUC-MSCs will be administered intravenously as adjunctive therapy on day 0 at a dose of 1×106 cells/kg with a total volume of 100 mL diluted with normal saline through 120 mL/hour intravenous central line infusion in the interventional cohort. Placebo (normal saline) will also be administered through 120 mL/hour intravenous central line infusion at the same quantity (total volume of 100 mL) in the observational cohort. The study is approved by Research Ethics Board of East Hospital/Tongji University, which has been registered on Chinese clinical trial registry (chictr.org.cn) and initiated from October 2021. All the participants will be followed at regular intervals for 1 year. Funding is from the 'National Natural Science Foundation, China and top-level clinical discipline project of Shanghai Pudong'. This study is the first trial to assess the safety and efficacy of HUC-MSCs for the treatment of sepsis induced by pneumonia. The results will advance our understanding of the mode of action of HUC-MSCs and will also be critical for the design of future investigation in larger randomised controlled trials in multicentre. These data will offer insight into defining endpoints, key biomarkers and sample size determination.Ethics and disseminationThis study has been approved by the Research Ethics Board of East Hospital, Tongji University (Shanghai, China), which has accepted responsibility for supervising all aspects of the study (DFSC-2021(CR-04). The results of this study will be presented at both national and international conferences and be considered for publication in a peer-reviewed scientific journal. All the results presented in this study will be of group data, therefore, individual participants will not be identifiable.Trial registration numberChiCTR2100050544, the trial is now at the stage of pre-results.

Dataset Information

Efficacy of umbilical cord mesenchymal stem cell transfusion for the treatment of severe AKI: a protocol for a randomised controlled trial.

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Publications

Efficacy of umbilical cord mesenchymal stem cell transfusion for the treatment of severe AKI: a protocol for a randomised controlled trial.

Similar Datasets

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