scholarly journals Treatment of Severe COVID-19 with human Umbilical Cord Mesenchymal Stem Cells

2020 ◽  
Author(s):  
Lei Shu ◽  
Changming Niu ◽  
Ruyou Li ◽  
Tingrong Huang ◽  
Yan Wang ◽  
...  

Abstract Background COVID-19 is a highly infectious respiratory disease. No effective therapeutics have yet been proved for treating of severe COVID-19. Objectives To determine whether human Umbilical Cord Mesenchymal Stem Cells infusion may be effectiveness and safety in the treatment of severe COVID-19. Methods The severe COVID-19 randomly divided into 2 groups, standard treatment group and standard treatment plus hUC-MSCs infusion group. The incidence of severe patients aggravated to critically illness, 28-day mortality, clinical symptoms improvement, time to clinical symptoms improvement, hematologic indicators including C-reaction protein, lymphocyte number, interleukin 6 and imaging changes were observed and compared between two groups. Measurements and Main Results The incidence of severe patients aggravated to critically illness and 28-day mortality were 0 in hUC-MSCs treatment group, while 4 patients in control group were deteriorated to critical illness and been used invasive ventilation, 3 of them died, and 28-day mortality was 10.34%. In hUC-MSCs treatment group, the time to clinical improvement was shorter, clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation had improved obviously began the third day of stem cells infusion, and reached the significant difference on the day 7, CRP and IL-6 were significantly decreased from day 3 of infusion, the time for lymphocyte count returned to normal range was significant faster, and lung inflammation absorption was significantly shorter from CT imaging. Conclusions Intravenous transplantation of hUC-MSCs is a safe and effective way that can be considered as salvage and priority choice in the treatment of severe COVID-19.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yan Mi

Abstract Background and Aims Acute kidney injury( AKI) is one of the most common complications of decompensated cirrhosis, and it primarily presents as a sharp decrease in glomerular filtration rate, rapid increase in serum creatinine( SCr) and urea nitrogen. And the search for specific and safe treatment has been a research hot spot in recent years. In this article, the effect of human umbilical cord mesenchymal stem cells on carbon tetrachloride (CCl4)-induced liver fibrosis (HF) in rats with acute kidney injury and the possible mechanism are investigated. Method Human umbilical cord blood mesenchymal stem cells were sub-cultured by adherent method, and the cells were identified by morphological observation, cell phenotypic analysis and multi-directional differentiation potential analysis methods. WASTA rats were randomly divided into control group, cirrhosis model group and treatment group, with 10 rats in each group. Model group and treatment group were injected with CCl4-olive oil (1:1) solution 3 mL·kg -1, and the control group was given the same amount of olive oil for intervention, twice a week for 8 weeks. Rats in treatment group were administrated wth Human umbilical cord mesenchymal stem cells (2 × 109 /L) via the tail vein at the 5th week after injection of CCl4-olive oil solution, but the other rats were injected with 0.9% normal saline, once a week for 6 weeks. After the intervention, Serum, kidneys and 24 hours urine of rats in each group were collected, which were applied for a detection of serum creatinine and urea nitrogen, malondialdehyde (MDA), NO content and superoxide dismutase (SOD), as well as renal pathological examination. Results 1.In vitro, umbilical cord blood mesenchymal stem cells was passaged to the third generation, and the morphology was uniform and spiraled. Phenotypic analysis showed that the positive rates of stem cell markers CD29, CD44 and CD105 were all greater than 95%, the positive rate of HLA-DR (graft-versus-host disease-associated factor) less than 10%, and the positive rate of CD34 and CD45 lower than 20% (Figure 1). 2. Compared with the cirrhotic model group, MDA content of serum and kidney in model group significantly decreased under the effect of mesenchymal stem cell (p <0.01) (Table 1). 3. The normal group had normal liver tissue structure, ordered liver cells, no hepatic edema, and no lesions. In the model group, large-area lesions, including edema of liver cells, rupture of cell membranes, and infiltration of inflammatory cells, had appeared. Compared with the model group, Hepatocellular necrosis, edema, and inflammatory cell infiltration were significantly improved after transplanting Human umbilical cord mesenchymal stem cells (Figure 2). 4.In the model group, the rat renal tubules disappeared and the lumen was disordered. After injection of Human umbilical cord mesenchymal stem cells, renal tubular and renal interstitial damage is improved and the thickening of glomerular basement membrane is reduced (Figure 3). Conclusion In CCl4-induced liver cirrhosis model rats, human umbilical cord mesenchymal stem cells can protect the kidney by reducing free radicals and cellular lipid peroxidation in vivo.


2021 ◽  
Vol 11 (9) ◽  
pp. 1838-1843
Author(s):  
Xiaohong Zhou ◽  
Xuzhong Hao ◽  
Feifei He

To investigate whether exosomes (exo) derived from human umbilical cord mesenchymal stem cells (huMSCs) and microRNA (miRNA)-342 have a protective effect on severe acute pancreatitis (SAP). Human umbilical cord blood was collected to extract huMSC-exo. With sham-operated mice as control group (n = 10), the other mice were induced to SAP model (n = 20), while 10 of the SAP mice received treatment with huMSC-exo. ELISA was performed to determine amylase and TAP level as well as inflammatory factors and HE staining to evaluate pathological changes of pancreatic tissue. The expression of miR-342 and Shh, Ptchl, and Smo in the Hh signal pathway was detected using RT-qPCR. The expression of miR-342 and the mRNA expression of Shh, Ptchl, and Smo was higher than that in model group (p < 0.05). The level of serum amylase, trypsinogen, and IFN-γ,Fasl, and IL-6 was upregulated in pancreas tissues of SAP mice relative to healthy mice, but their levels were decreased upon treatment with huMSC-exo and slightly higher than those of the control group, just not significantly. Collectively, the huMSC-exo may activate the Hh signaling pathway by regulating the expression of miR-342 increasing the expression of Shh, Ptchl, and Smo, and thereby healing of damaged pancreatic tissues in SAP.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247662
Author(s):  
Jingjing He ◽  
Desheng Kong ◽  
Zhifen Yang ◽  
Ruiyun Guo ◽  
Asiamah Ernest Amponsah ◽  
...  

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.


2020 ◽  
pp. 897-906
Author(s):  
H CHI ◽  
H SON ◽  
D CHUNG ◽  
L HUAN ◽  
T DIEM ◽  
...  

The cytoskeleton plays a key role in cellular proliferation, cell-shape maintenance and internal cellular organization. Cells are highly sensitive to changes in microgravity, which can induce alterations in the distribution of the cytoskeletal and cell proliferation. This study aimed to assess the effects of simulated microgravity (SMG) on the proliferation and expression of major cell cycle-related regulators and cytoskeletal proteins in human umbilical cord mesenchymal stem cells (hucMSCs). A WST-1 assay showed that the proliferation of SMG-exposed hucMSCs was lower than a control group. Furthermore, flow cytometry analysis demonstrated that the percentage of SMG-exposed hucMSCs in the G0/G1 phase was higher than the control group. A western blot analysis revealed there was a downregulation of cyclin A1 and A2 expression in SMG-exposed hucMSCs as well. The expression of cyclin-dependent kinase 4 (cdk4) and 6 (cdk6) were also observed to be reduced in the SMG-exposed hucMSCs. The total nuclear intensity of SMG-exposed hucMSCs was also lower than the control group. However, there were no differences in the nuclear area or nuclear-shape value of hucMSCs from the SMG and control groups. A western blot and quantitative RT-PCR analysis showed that SMG-exposed hucMSCs experienced a downregulation of β-actin and α-tubulin compared to the control group. SMG generated the reorganization of microtubules and microfilaments in hucMSCs. Our study supports the idea that the downregulation of major cell cycle-related proteins and cytoskeletal proteins results in the remodeling of the cytoskeleton and the proliferation of hucMSCs.


2020 ◽  
Author(s):  
Xue-Cheng Sun ◽  
Hu Wang ◽  
Jian-Hui Li ◽  
Dan Zhang ◽  
Xu Ma ◽  
...  

Abstract Background: Alveolar cleft is a kind of cleft lip and palate, which seriously affects the physical and mental health of patients. In this study, a similar model of human alveolar cleft phenotype was established in rabbits to evaluate the effect of bone collagen particles combined with human umbilical cord mesenchymal stem cells (hUC-MSCs) on the repair of alveolar cleft. Materials &Methods : In this study, 24 adult Japanese white rabbits (JWRs) were selected and randomly divided into 4 groups. Including normal group, control group, materials group and MSCs group. The model of alveolar cleft was established by removing the incisors on the left side of the upper jaw. The normal group did not receive any treatment. In the control group, the incisors were removed and sutured directly. In the material group, the incisor were removed, then filled with bone collagen particles, and finally sutured. In the MSCs group, the incisors were first removed, then filled with bone collagen granules incubated by hUC-MSCs, and then stitched. Blood biochemical analysis was performed 3 months after the operation. Skull tissues were collected for gross observation, and micro-focus computerized tomography (micro-CT) analysis. Paraffin sections were prepared for histological and immunohistochemical staining. Results: The bone collagen particles and hUC-MSCs are not biotoxic and can promote alvenlus regeneration. Bone collagen particles combined with hUC-MSCs were much better than those used alone in inducing bone repair and regeneration. Conclusions: HUC-MSCs can be used as a bone generation inducer combined with bone materials for bone regeneration and repair. Keywords: alveolar cleft,Bone collagen particle, hUC-MSCs (human umbilical cord mesenchymal stem cells),micro-focus computerized tomography (micro-CT)


2015 ◽  
Vol 1 (1) ◽  
pp. 70
Author(s):  
Taghreed A. Aldosary ◽  
Hasan Uludag ◽  
Michael R. Doschak ◽  
Tarek El-Bialy

Background: Tissue engineering involves using different types of stem cells. One of the roadblocks in tissue engineering is the scant supply of stem cells. The potential use of human umbilical cord peri-vascular Cells (HUCPVCs) has recently been considered as an important cell source for tissue engineering applications. The objective of this study was to explore the effect of low intensity pulsed ultrasound (LIPUS) on HUCPVCs. Materials and methods: HUCPVCs were divided into two groups: treatment group which received 30 mW/cm2 LIPUS for 10 minutes (1, 7, and 14 days) and control group which received sham treatment. The study groups were evaluated for cell count, alkaline phosphatase (ALP) activity, DNA-content, gene expression, and immunophenotype. Results: There was no significant differences in cell count, ALP, DNA-content, and CD-90 between LIPUS and control groups. A significantly higher expression of OSP and PCNA was observed on day 14 in LIPUS treatment group. Conclusion: LIPUS application for 10 minutes per day for 14 days enhanced OSP and PCNA expression without significant increase in cell count of HUCPVCs. Future research may aim at exploring different LIPUS applications (different time and frequency) to optimize HUCPVCs proliferation.


2020 ◽  
Author(s):  
Lei Shu ◽  
Changming Niu ◽  
Ruyou Li ◽  
Tingrong Huang ◽  
Yan Wang ◽  
...  

Abstract Background: COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19. Objectives: To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19. Methods: Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups. Measurements and Main Results: The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34% . In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group. Conclusions: Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19.


2019 ◽  
Author(s):  
Xian Wu ◽  
Yunqiu Xia ◽  
Ou Zhou ◽  
Yan Song ◽  
Xianhong Zhang ◽  
...  

Abstract Background: Bronchopulmonary dysplasia (BPD) is a complex lung pathological lesion secondary to multiple factors and one of the most common chronic lung diseases with 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 intravenous 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 intravenous hUC-MSCs in children with severe BPD. Its results will provide a new evidence-based therapy for severe BPD.


2019 ◽  
Vol 52 (1) ◽  
pp. 36
Author(s):  
Nike Hendrijantini

Background: Mesenchymal stem cells (MSCs) and scaffold combination constitute a promising approach currently adopted for tissue engineering. Umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are easily obtained and non-invasive. Gelatine and alginate constitute a biocompatible natural polymer scaffold. At present, a cytotoxicity comparison of gelatine and alginate to hUC-MSCs is not widely conducted Purpose: This study aimed to compare the cytotoxicity of gelatine and alginate in hUC-MSCs in vitro. Methods: Isolation and culture were performed on hUC-MSCs derived from healthy full-term neonates. Flow Cytometry CD90, CD105 and CD73 phenotype characterization was performed in passage 4. 3-(4,5-dimethythiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay was performed to measure the cytotoxicity. The three sample groups were: (T1) hUC-MSCs with α-MEM (alpha-minimum essential medium) solution as control; (T2) hUC-MSCs with gelatine; (T3) hUC-MSCs with alginate Results: Flow cytometry of hUC-MSCs displayed positive CD90, CD105 and CD73 surface markers. Gelatine and alginate had no effect on the viability of hUC-MSCs and no statistically significant difference (p>0.05) of cytotoxicity between gelatine and alginate to hUC-MSCs. Conclusion: Gelatine and alginate proved to be non-toxic to hUC-MSCs in vitro.


2019 ◽  
Author(s):  
Xiaoli Lu ◽  
Guangzhi Liu ◽  
Lenan Cheng ◽  
Licong Ge ◽  
ZiYi Zhao ◽  
...  

Abstract Objective:To investigate the effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on apoptosis and proliferation of human ovarian cancer SKOV3 cells and to explore mechanism.Methods:hUC-MSCs were isolated and cultured by tissue block adherent culture method. The hUC-MSCs phenotype were identified by flow cytometry. The hUC-MSCs lysate and conditioned medium,directly combine were used to treat SKOV3 cells.The effects on the proliferation,apoptosis,mechanism of SKOV3 cells were examined by cell counting kit-8(CCK-8),Annexin V-FITC/PI,quantitative real time polymerase chain reaction(RT-qPCR) and spheroid formation assays.Establish ovarian cancer xenograft models,1X 106 hUC-MSCs and 2 X 106 hUC-MSCs were administrated into the mice t rear back tumor tissue. After three injections of hUC-MSCs, the nude mice were sacrificed after 1 week of observation.Remove tumor tissue. Observed tumor volume changes every 3 days after the start of the experiment. The expression of CD34 and VEGF were detected by immunohistochemistry.Results:Human umbilical cord mesenchymal stem cells were cultured and isolated from tissue block. Flow cytometry results revealed that the hUC-MSCs marks CD44 and CD29, but not CD45 and CD34 were expressed on obtained cells. The apoptosis of SKOV3 cells was induced by hUC-MSCs lysate, conditioned medium and Transwell co-culture method in SKOV3 cells, and the apoptosis rate was higher with increasing concentration. hUC-MSCs conditioned medium and Transwell co-culture method can inhibit cell proliferation. After adding experimental factors, the conditioned medium and Transwell co-culture method can down-regulate the transcription of PI3KCA, AKT and BCL-2 genes in SKOV3 cells, and up-regulate the Caspase-3 gene.The tumor volume of the experimental group was smaller than that of the control group during the observation period. The expression levels of CD34 and VEGF in the experimental group were significantly lower than those in the control group(P<0.05).Conclusion: The conditioned medium of hUC-MSCs and the co-culture method of hUC-MSCs and SKOV3 can significantly inhibit the proliferation of SKOV3 cells, which is mainly achieved by inhibiting PI3K/AKT signaling pathway. hUC-MSCs can inhibit the growth of subcutaneous subcutaneous transplantation and the expression of CD34 and VEGF in ovarian cancer. It provides a new idea for the treatment of ovarian cancer.


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