scholarly journals Simulated Microgravity Reduces Proliferation and Reorganizes the Cytoskeleton of Human Umbilical Cord Mesenchymal Stem Cells

2020 ◽  
pp. 897-906
Author(s):  
H CHI ◽  
H SON ◽  
D CHUNG ◽  
L HUAN ◽  
T DIEM ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Western Blot ◽  
Umbilical Cord ◽  
Simulated Microgravity ◽  
Cellular Proliferation ◽  
Cytoskeletal Proteins ◽  
Control Group ◽  
Human Umbilical Cord

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.

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells (huMSCs) Carrying MicroRNA-342 Relieve Protect Severe Acute Pancreatitis Injury (SAP)

2021 ◽  
Vol 11 (9) ◽  
pp. 1838-1843
Author(s):  
Xiaohong Zhou ◽  
Xuzhong Hao ◽  
Feifei He
Keyword(s):  
Stem Cells ◽  
Acute Pancreatitis ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Severe Acute Pancreatitis ◽  
Pancreatic Tissue ◽  
Inflammatory Factors ◽  
Control Group ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord

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.

scholarly journals Bone collagen particles combined with hUC-MSCs to repair alveolar cleft in rabbits

2020 ◽  
Author(s):  
Xue-Cheng Sun ◽  
Hu Wang ◽  
Jian-Hui Li ◽  
Dan Zhang ◽  
Xu Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Computerized Tomography ◽  
Umbilical Cord ◽  
Normal Group ◽  
Bone Collagen ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Micro Ct ◽  
Alveolar Cleft

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)

P0520EFFECT OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS ON SECONDARY ACUTE KIDNEY INJURY IN RATS WITH LIVER CIRRHOSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yan Mi
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Olive Oil ◽  
Umbilical Cord ◽  
Kidney Injury ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Model Group

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 &lt;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.

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

2019 ◽  
Author(s):  
Xian Wu ◽  
Yunqiu Xia ◽  
Ou Zhou ◽  
Yan Song ◽  
Xianhong Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Randomized Controlled Trial ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Controlled Trial ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Safety And Efficacy ◽  
Randomized Controlled

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.

scholarly journals Dodging COVID-19 infection: low expression and localization of ACE2 and TMPRSS2 in multiple donor-derived lines of human umbilical cord-derived mesenchymal stem cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jonathan J. Hernandez ◽  
Doyle E. Beaty ◽  
Logan L. Fruhwirth ◽  
Ana P. Lopes Chaves ◽  
Neil H. Riordan
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Mesenchymal Stem Cells ◽  
Western Blot ◽  
Viral Infection ◽  
Umbilical Cord ◽  
Quantitative Polymerase Chain Reaction ◽  
Human Umbilical Cord ◽  
Human Lung Tissue ◽  
Low Expression

Abstract Background Mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have immunomodulatory properties that are of interest to treat novel coronavirus disease 2019 (COVID-19). Leng et al. recently reported that hUC-MSCs derived from one donor negatively expressed Angiotensin-Converting Enzyme 2 (ACE2), a key protein for viral infection along with Transmembrane Serine Protease 2 (TMPRSS2). The purpose of this study was to quantify the expression of ACE2 and TMPRSS2 in hUC-MSCs lots derived from multiple donors using molecular-based techniques in order to demonstrate their inability to be a host to SARS-CoV-2. Methods Expression of ACE2 and TMPRSS2 was analyzed in 24 lots of hUC-MSCs derived from Wharton's jelly via quantitative polymerase chain reaction (qPCR), Western Blot, immunofluorescence and flow cytometry using 24 different donors. Results hUC-MSCs had significantly lower ACE2 (p = 0.002) and TMPRSS2 (p = 0.008) expression compared with human lung tissue homogenates in Western blot analyses. Little to no expression of ACE2 was observed in hUC-MSC by qPCR, and they were not observable with immunofluorescence in hUC-MSCs cell membranes. A negative ACE2 and TMPRSS2 population percentage of 95.3% ± 15.55 was obtained for hUC-MSCs via flow cytometry, with only 4.6% ACE2 and 29.5% TMPRSS2 observable positive populations. Conclusions We have demonstrated negative expression of ACE2 and low expression of TMPRSS2 in 24 lots of hUC-MSCs. This has crucial implications for the design of future therapeutic options for COVID-19, since hUC-MSCs would have the ability to “dodge” viral infection to exert their immunomodulatory effects.

Effect of umbilical cord mesenchymal stem cells in human ovarian cancer SKOV3 cells

2019 ◽  
Author(s):  
Xiaoli Lu ◽  
Guangzhi Liu ◽  
Lenan Cheng ◽  
Licong Ge ◽  
ZiYi Zhao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Umbilical Cord ◽  
Culture Method ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Skov3 Cells ◽  
Experimental Group

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.

scholarly journals Proliferative Effect of Aqueous Extract of Sea Cucumber (Holothuria Parva) Body Wall on Human Umbilical Cord Mesenchymal Stromal/stem Cells

2021 ◽  
Author(s):  
Poorya Rasekh ◽  
Ali Kameli ◽  
Arezoo Khoradmehr ◽  
Neda Baghban ◽  
Gholamhossein Mohebbi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Umbilical Cord ◽  
Aqueous Extract ◽  
Sea Cucumber ◽  
Body Wall ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Stromal Stem Cells

Abstract Background: The sea cucumber potentials for stem cell proliferation induction and their mechanisms of bioactive compounds in its extract have been studied. Human umbilical cord mesenchymal stromal/stem cells (hUC-MSCs) were exposed to aqueous extract of Holothuria parva body wall. Methods: Using GC-MS analysis on aqueous extract of H. parva, proliferative molecules were detected. The extract concentrations of 5, 10, 20, 40, and 80 µg/mL and 10 and 20 ng/mL of human epidermal growth factor (EGF) as positive controls were used. MTT proliferation, cell count, viability, and cell cycle assays were performed. Using Western blot analysis, effects of aqueous extract of H. parva and EGF on cell proliferation markers were detected. Computational modeling done to detect effective proliferative compounds in aqueous extract of H. parva. Results: MTT assay showed that the 10, 20, and 40 µg/mL aqueous extract of H. parva had proliferative effects on hUC-MSCs. Count of the cells treated with the 20 µg/mL of the extract was increased faster and higher than the control group (P<0.05). This concentration of extract did not have significant effects on hUC-MSCs viability. The cell cycle assay of hUC-MSCs showed that percent of cells in the G2 stage of the extract was biologically higher than the control group (P>0.05). Expression of the cyclin D1, cyclin D3, cyclin E, HIF-1α, and TERT were increased comparing with the control group. Moreover, expression of the p21 and PCNA decreased after treating hUC-MSCs with the extract. However, the CDC-2/cdk-1 and ERK1/2 had almost the same expression as the control group. The expression of the cdk-4 and cdk-6 was decreased after treatment with the extract. Between the detected compounds, 1-methyl-4-(1-methylethenyl)-benzene showed better affinity to cdk-4 and p21 than tetradecanoic acid. Conclusions: The H. parva aqueous extract showed proliferative potential on the hUC-MSCs.

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

2019 ◽  
Author(s):  
Xian Wu ◽  
Yunqiu Xia ◽  
Ou Zhou ◽  
Yan Song ◽  
Xianhong Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Randomized Controlled Trial ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Bronchopulmonary Dysplasia ◽  
Controlled Trial ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Safety And Efficacy ◽  
Randomized Controlled

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 poor prognosis, especially in preterm infants with moderate and 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 moderate and 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 moderate and severe BPD. In this study, 57 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=19, 1 million cells/kg) or a high dose of hUC-MSCs (n=19, 5 million cells/kg) in combination with traditional supportive treatments for BPD. The patients in the control group (n=19) will be treated with traditional supportive treatments alone without receiving hUC-MSCs treatment. The primary outcome measures will be the accumulative duration of oxygen therapy. Follow-up assessments will be performed at 1, 3, 6, 12, 24 months after interventions. 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 moderate and severe BPD. Results of the trial will provide a new evidence-based therapy for moderate and severe BPD. Trial Registration ClinicalTrials.gov, NCT03601416. Registered on 26th July 2018.

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 ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Umbilical Cord ◽  
Standard Treatment ◽  
Clinical Symptoms ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Significant Difference ◽  
Critically Illness

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.

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