scholarly journals Exosomes derived from three-dimensional cultured human umbilical cord mesenchymal stem cells ameliorate pulmonary fibrosis in a mouse silicosis model

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Chunjie Xu ◽  
Jing Zhao ◽  
Qiuyue Li ◽  
Lin Hou ◽  
Yan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pulmonary Fibrosis ◽  
Umbilical Cord ◽  
Three Dimensional ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Promising Alternative ◽  
Cell Based Therapy

Abstract Background Silicosis is an occupational respiratory disease caused by long-term excessive silica inhalation, which is most commonly encountered in industrial settings. Unfortunately, there is no effective therapy to delay and cure the progress of silicosis. In the recent years, stem cell therapy has emerged as an attractive tool against pulmonary fibrosis (PF) owing to its unique biological characteristics. However, the direct use of stem cells remains limitation by many risk factors for therapeutic purposes. The exclusive utility of exosomes secreted from stem cells, rather than cells, has been considered a promising alternative to overcome the limitations of cell-based therapy while maintaining its advantages. Methods and results In this study, we first employed a three-dimensional (3D) dynamic system to culture human umbilical cord mesenchymal stem cell (hucMSC) spheroids in a microcarrier suspension to yield exosomes from serum-free media. Experimental silicosis was induced in C57BL/6J mice by intratracheal instillation of a silica suspension, with/without exosomes derived from hucMSC (hucMSC-Exos), injection via the tail vein afterwards. The results showed that the gene expression of collagen I (COL1A1) and fibronectin (FN) was upregulated in the silica group as compared to that in the control group; however, this change decreased with hucMSC-Exo treatment. The value of FEV0.1 decreased in the silica group as compared to that in the control group, and this change diminished with hucMSC-Exo treatment. These findings suggested that hucMSC-Exos could inhibit silica-induced PF and regulate pulmonary function. We also performed in vitro experiments to confirm these findings; the results revealed that hucMSC-Exos decreased collagen deposition in NIH-3T3 cells exposed to silica. Conclusions Taken together, these studies support a potential role for hucMSC-Exos in ameliorating pulmonary fibrosis and provide new evidence for improving clinical treatment induced by silica.

Systematic Intracellular Biocompatibility Assessments of Superparamagnetic Iron Oxide Nanoparticles in Human Umbilical Cord Mesenchyme Stem Cells in Testifying Its Reusability for Inner Cell Tracking by MRI

2019 ◽  
Vol 15 (11) ◽  
pp. 2179-2192
Author(s):  
Yuanyuan Xie ◽  
Wei Liu ◽  
Bing Zhang ◽  
Bin Wang ◽  
Liudi Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Umbilical Cord ◽  
Cell Tracking ◽  
Superparamagnetic Iron Oxide ◽  
Human Umbilical Cord ◽  
Cell Based Therapy

Until now, there is no effective method for tracking transplanted stem cells in human. Ruicun (RC) is a new ultra-small SPIONs agent that has been approved by China Food and Drug Administration for iron supplementation but not as a stem cell tracer in clinic. In this study, we demonstrated magnetic resonance imaging-based tracking of RC-labeled human umbilical cord derived mesenchymal stem cells (MSCs) transplanted to locally injured site of rat spinal cords. We then comprehensively evaluated the safety and quality of the RC-labeled MSCs under good manufacturing practicecompliant conditions, to investigate the feasibility of SPIONs for inner tracking in stem cell-based therapy (SCT). Our results showed that RC labeling at appropriate dose (200 μg/mL) did not have evident impacts on characteristics of MSCs in vitro, demonstrating safety, non-carcinogenesis, and non-tissue inflammation in vivo. The systematic assessments of intracellular biocompatibility indicated that the RC labeled MSCs met with mandatory requirements and standards for law-regulation systems regarding SCT, facilitating translation of cell-tracking technologies to clinical trials.

scholarly journals Chronic Toxicity Test in Cynomolgus Monkeys For 98 Days with Repeated Intravenous Infusion of Cynomolgus Umbilical Cord Mesenchymal Stem Cells

2017 ◽  
Vol 43 (3) ◽  
pp. 891-904 ◽  
Author(s):  
Jie He ◽  
Guang-ping Ruan ◽  
Xiang Yao ◽  
Ju-fen Liu ◽  
Xiang-qing Zhu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Umbilical Cord ◽  
Intravenous Infusion ◽  
Dose Group ◽  
High Dose ◽  
Human Umbilical Cord ◽  
Cynomolgus Monkeys ◽  
Cell Based Therapy

Background/Aims: Stem cell-based therapy is attractive in many clinical studies, but current data on the safety of stem cell applications remains inadequate. This study observed the safety, immunological effect of cynomolgus monkey umbilical cord mesenchymal stem cells (mUC-MSCs) injected into cynomolgus monkeys, in order to evaluate the safety of human umbilical cord mesenchymal stem cells (hUC-MSCs) prepared for human clinical application. Methods: Eighteen cynomolgus monkeys were divided into three groups. Group 1 is control group, Group 2 is low-dose group, Group 3 is high-dose group. After repeated administrations of mUC-MSCs, cynomolgus monkeys were observed for possible toxic reactions. Results: During the experiment, no animal died. There were no toxicological abnormalities in body weight, body temperature, electrocardiogram, coagulation and pathology. In the groups 2 and 3, AST and CK transiently increased, and serum inorganic P slightly decreased. All animals were able to recover at 28 days after the infusion was stopped. In the groups 2 and 3, CD3+ and IL-6 levels significantly increased, and recovery was after 28 days of infusion. There were no obvious pathological changes associated with the infusion of cells in the general and microscopic examinations. Conclusions: The safe dosage of repeated intravenous infusion of mUC-MSCs in cynomolgus monkeys is 1.0 × 107/kg, which is 10 times of that in clinical human use.

scholarly journals Dual Effects of Hypoxia-Inducible Factors-1 Alpha in Bleomycin-Induced Pulmonary Fibrosis Treated by Human Umbilical Cord Mesenchymal Stem Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Hongpeng Zhang ◽  
Hao Wang ◽  
Yong Xia ◽  
Nianmin Qi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Pulmonary Fibrosis ◽  
Umbilical Cord ◽  
Smooth Muscle Actin ◽  
A549 Cells ◽  
Human Umbilical Cord ◽  
Therapeutic Administration

Pulmonary fibrosis (PF) is a kind of lung disease characterized by scar formation and inflammation damage. Mesenchymal stem cells (MSCs) are considered a promising therapy because of multidirectional differentiation and immune regulation. Our research was designed for identifying the preventative defensive ability and therapeutic effect of human umbilical cord mesenchymal stem cells (HUCMSCs). HUCMSCs were administered before or after bleomycin injection in different groups of C57BL/6 mice. We calculated the survival time of mice, the lung coefficients, contents of hydroxyproline, and pathological scores. The expression levels of HIF-1α (hypoxia-inducible factor-1α), α-SMA (α-smooth muscle actin), γH2AFX (γH2A histone family, member X), ZO-1 (zonula occludens-1), ROS (reactive oxygen species) content, and proliferation ability of A549 cells were detected after treatment with bleomycin and HUCMSCs conditioned medium (HUCMSCs-CM), respectively, or together in vitro. In addition, we examined the secretome of HUCMSCs in regular and inflammatory stimulation conditions. Our results demonstrated that prophylactic HUCMSC administration before bleomycin-induced modeling process could significantly meliorate damage to pulmonary fibrosis. After the deletion of HIF-1α, damage markers in A549 cells were significantly reduced in therapeutic administration condition. However, it was the opposite in prophylactic administration condition. The results confirmed that HUCMSCs had available preventive effect on bleomycin-induced pulmonary fibrosis in vivo and in vitro. However, it may have a negative effect in therapeutic administration condition because of the dual effect of HIF-1α.

scholarly journals ID: 1032 Differentiation Potential and Characteristics of Mesenchymal Stem Cells Isolated from Human Umbilical Cord membrane to Hepatocyte-like Cells

2017 ◽  
Vol 4 (S) ◽  
pp. 107
Author(s):  
Trung Kien Do ◽  
Van Hanh Nguyen ◽  
Huu Duc Nguyen ◽  
Chu Hoang Ha
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Umbilical Cord ◽  
Gene Transfection ◽  
Human Umbilical Cord ◽  
Specific Marker ◽  
Differentiation Potential

Recent studies indicated that Mesenchymal stem cell has become a potential objective for therapy. In this study, umbilical cord cells were isolated and analyzed the expression of mesenchymal stem cells specific markers then they were differentiated into hepatocyte-like cells by DMSO and Gene transfection. Umbilical cord mesenchymal stem cell (MSC) was isolated by explant culture in media DMEM/F12, complementing with growth factors EGF, FGF and IST. After that, they were exposured to DMSO with three concentrations: 0.01%, 0.1%, 1% and another group was transfection with HNF4α by Lipofectamin LX plus. The cells were analyzed at 1, 2, 3, and 4 weeks after treatment. The cells isolation was shown the positive with markers CD73, CD34, CD86, CD90, CD105, eras, Oct 1, GATA, and negative with markers HNF4α, Alb and G6P. In group 0,1% DMSO treatment, after 3 weeks the cells were positive with markers HNF4α but it was also negative with markers Alb and G6P. In the transfection group, the cell expresses HNF4α at three weeks after treatment. Although our results exposure that the umbilical cord mesenchymal stem cells expressed hepatic specific marker after DMSO induced and DNA treatment. So it will be necessary to optimize research conditional and investigate the hepatic functions of these cells in a longer in vitro culture.

scholarly journals Microenvironment Influences on Human Umbilical Cord Mesenchymal Stem Cell-Based Bone Regeneration

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Lingling E ◽  
Rongjian Lu ◽  
Jianwei Sun ◽  
Hongbo Li ◽  
Wen Xu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Umbilical Cord ◽  
Three Dimensional ◽  
Human Umbilical Cord ◽  
Mineralized Matrix ◽  
Three Dimensional Culture

The microenvironment, or niche, regulates stem cell fate and improves differentiation efficiency. Human umbilical cord mesenchymal stem cells (hUC-MSCs) are ideal cell source for bone tissue engineering. However, the role of the microenvironments in hUC-MSC-based bone regeneration is not yet fully understood. This study is aimed at investigating the effects of the in vitro culture microenvironment (hUC-MSCs, nano-hydroxyapatite/collagen/poly (L-lactide) (nHAC/PLA), osteogenic media (OMD), and recombinant human bone morphogenetic protein-7 (rhBMP-7)) and the in vivo transplanted microenvironment (ectopic and orthotopic) on bone regeneration ability of hUC-MSCs. The isolated hUC-MSCs showed self-renewal potential and MSCs’ characteristics. In the in vitro two-dimensional culture microenvironment, OMD or OMD with rhBMP-7 significantly enhanced hUC-MSCs’ osteocalcin immunofluorescence staining, alkaline phosphatase, and Alizarin red staining; OMD with rhBMP-7 exhibited the highest ALP secretion and mineralized matrix formation. In the in vitro three-dimensional culture microenvironment, nHAC/PLA supported hUC-MSCs’ adhesion, proliferation, and differentiation; the microenvironment containing OMD or OMD and rhBMP-7 shortened cell proliferation progression and made osteogenic differentiation progression advance; rhBMP-7 significantly attenuated the inhibiting effect of OMD on hUC-MSCs’ proliferation and significantly enhanced the promoting effect of OMD on gene expression and protein secretion of osteogenic differentiation markers, calcium and phosphorous concentration, and mineralized matrix formation. The in vitro three-dimensional culture microenvironment containing OMD and rhBMP-7 induced hUC-MSCs to form the most new bones in ectopic or orthotopic microenvironment as proved by microcomputed tomography and hematoxylin and eosin staining, but bone formation in orthotopic microenvironment was significantly higher than that in ectopic microenvironment. The results indicated that the combination of in vitro hUC-MSCs+nHAC/PLA+OMD+rhBMP-7 microenvironment and in vivo orthotopic microenvironment provided a more optimized niche for bone regeneration of hUC-MSCs. This study elucidates that hUC-MSCs and their local microenvironment, or niche, play an important role in hUC-MSC-based bone regeneration. The endogenously produced BMP may serve an important regulatory role in the process.

scholarly journals Bone Regeneration by Nanohydroxyapatite/Chitosan/Poly(lactide-co-glycolide) Scaffolds Seeded with Human Umbilical Cord Mesenchymal Stem Cells in the Calvarial Defects of the Nude Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Fei Wang ◽  
Xiao-Xia Su ◽  
Yu-Cheng Guo ◽  
Ang Li ◽  
Yin-Cheng Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Umbilical Cord ◽  
Nude Mice ◽  
Fluorescence Labeling ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Calvarial Defects

In the preliminary study, we have found an excellent osteogenic property of nanohydroxyapatite/chitosan/poly(lactide-co-glycolide) (nHA/CS/PLGA) scaffolds seeded with human umbilical cord mesenchymal stem cells (hUCMSCs)in vitroand subcutaneously in the nude mice. The aim of this study was to further evaluate the osteogenic capacity of nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice. Totally 108 nude mice were included and divided into 6 groups: PLGA scaffolds + hUCMSCs; nHA/PLGA scaffolds + hUCMSCs; CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds without seeding; the control group (no scaffolds) (n=18). The scaffolds were implanted into the calvarial defects of nude mice. The amount of new bones was evaluated by fluorescence labeling, H&E staining, and Van Gieson staining at 4 and 8 weeks, respectively. The results demonstrated that the amount of new bones was significantly increased in the group of nHA/CS/PLGA scaffolds seeded with hUCMSCs (p<0.01). On the basis of previous studiesin vitroand in subcutaneous implantation of the nude mice, the results revealed that the nHA and CS also enhanced the bone regeneration by nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice at early stage.

Microbial stresses on human umbilical cord stem cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Didem Kart ◽  
Betül Çelebi-Saltik
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Umbilical Cord ◽  
Bacterial Load ◽  
Early Period ◽  
Stress Factors ◽  
Human Umbilical Cord ◽  
Antibacterial Effects ◽  
Hematopoietic Stem ◽  
Umbilical Cord Stem Cells

: Umbilical cord and cord blood are acceptable as attractive sources of mesenchymal and hematopoietic stem cells, since their collection is non-invasive, painless, and does not evoke the ethical concerns. Microorganism-stem cell interaction plays an important role in stem cell self-renewal, differentiation, secretion profile and death. In the literature, few researchers are examining the relationship between pathogenic and commensal bacteria with umbilical cord-derived Mesenchymal Stem Cells (MSCs). These relationships vary depending on the bacterial load and the presence of the immune cell in the environment. Several bacterial pathogens act in the regenerative capacity of MSCs by changing their phenotype, development and viability due to several stress factors that are created by a microorganism such as hypoxia, oxidative stress, etc. On the other hand, the anti-inflammatory and antibacterial effects of MSCs were shown and these phenomena increased when the number of bacteria was high but decreased in the presence of low amounts of bacteria. The antibacterial effects of MSCs increased in the early period of infection, while their effects were decreased in the late period with high inflammatory response and bacterial load. In this review, we discussed the microbial stresses on human umbilical cord stem cells.

scholarly journals Microvesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Stimulated by Hypoxia Promote Angiogenesis Both In Vitro and In Vivo

2012 ◽  
Vol 21 (18) ◽  
pp. 3289-3297 ◽  
Author(s):  
Hong-Chao Zhang ◽  
Xin-Bin Liu ◽  
Shu Huang ◽  
Xiao-Yun Bi ◽  
Heng-Xiang Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Human Umbilical Cord
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