scholarly journals Effect of Microenvironment on Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into HepatocytesIn VitroandIn Vivo

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Gai Xue ◽  
Xiaolei Han ◽  
Xin Ma ◽  
Honghai Wu ◽  
Yabin Qin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Liver Tissue ◽  
Human Umbilical Cord ◽  
Hepatic Differentiation ◽  
Differentiation Potential ◽  
Tissue Microenvironment

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are considered to be an ideal cell source for cell therapy of many diseases. The aim of this study was to investigate the contribution of the microenvironment to the hepatic differentiation potential of hUCMSCsin vitroandin vivoand to explore their therapeutic use in acute liver injury in rats. We established a new model to simulate the liver tissue microenvironmentin vivousing liver homogenate supernatant (LHS)in vitro. This induced environment could drive hUCMSCs to differentiate into hepatocyte-like cells within 7 days. The differentiated cells expressed hepatocyte-specific markers and demonstrated hepatocellular functions. We also injected hUCMSCs into rats with CCl4-induced acute hepatic injury. The hUCMSCs were detected in the livers of recipient rats and expressed the human hepatocyte-specific markers, suggesting that hUCMSCs could differentiate into hepatocyte-like cellsin vivoin the liver tissue microenvironment. Levels of biochemistry markers improved significantly after transplantation of hUCMSCs compared with the nontransplantation group (P<0.05). In conclusion, this study demonstrated that the liver tissue microenvironment may contribute to the differentiation of hUCMSCs into hepatocytes bothin vitroandin vivo.

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

Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo

2018 ◽  
Vol 373 (2) ◽  
pp. 379-393 ◽  
Author(s):  
Tao Zhang ◽  
Pan Wang ◽  
Yanxia Liu ◽  
Jiankang Zhou ◽  
Zhenqing Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Human Umbilical Cord ◽  
And Migration

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.

Cell Heterogeneity, Rather Than Cell Solvents Affects the Behavior of Mesenchymal Stem Cells in Vitro and Vivo

2020 ◽  
Author(s):  
Yong-Hong Wang ◽  
Ya-Chao Tao ◽  
Dong-Bo Wu ◽  
Meng-Lan Wang ◽  
Hong Tang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Survival Rates ◽  
Phosphate Buffer Solution ◽  
Human Umbilical Cord ◽  
Cell Heterogeneity ◽  
Hepatic Differentiation ◽  
Buffer Solution ◽  
Differentiation Potential

Abstract Background: Mesenchymal stem cells (MSCs) have been approved to treat various diseases, but they have to be expanded in vitro to gain sufficient cell doses. During the process of expansion, some obstacles remain to be addressed before MSCs translation to clinic. The purpose of this study was to investigate the effects of cell solvents and cell heterogeneity on the behavior of MSCs in vitro and vivo.Methods: Human umbilical cord MSCs (UC-MSCs) were dissolved in three different solvents: phosphate buffer solution (PBS), normal saline (NS) and dulbecco's modified eagle medium (DMEM). Their ultrastructure, viability and safety were explored and compared. MSCs from other two separate donors were grouped based on their mean diameters. The ultrastructure, proliferative and hepatic differentiation potential, senescent cell ratio and safety of the two UC-MSC aggregates were investigated and compared. The reason for mice death after UC-MSCs injection was further investigated.Results: The apoptosis rates, ultrastructure analysis and survival rates of mice among UC-MSCs in DMEM, NS and PBS were similar, and no significant differences were observed. The diameters of UC-MSCs of different sizes were measured. Cells with diameter of 15.58±3.813 μm were renamed as larger UC-MSC aggregates and cells with diameter of 19.14±4.885 μm were smaller aggregates. The mean diameter of larger MSC aggregates was significantly longer than that of smaller aggregates (p<0.01). Smaller MSCs had more potent proliferation potential and higher nucleus/ cytoplasm ratio than large ones. The number of cells positive for senescence-associated β-galactosidase staining was higher in larger UC-MSC aggregates. The survival rates of mice receiving 1×106 or 2×106 smaller MSCs were 100%, both higher than that receiving larger UC-MSCs sharing same amount. Meanwhile, the reason for mice death was explored and it revealed that larger UC-MSC aggregates were accumulated and evident in the pulmonary capillary lumen in dead mice.Conclusion: Solvents showed no significant effects on cell behavior, whereas, heterogeneity is quite prevalent in MSCs populations and may limit cell application, but it is easily overlooked. Hence it is necessary to establish a more precise standardization for culture-expanded MSCs and to improve MSCs manufacturing strategies.

scholarly journals Exposure to blue light stimulates the proangiogenic capability of exosomes derived from human umbilical cord mesenchymal stem cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Kun Yang ◽  
Dong Li ◽  
Meitian Wang ◽  
Zhiliang Xu ◽  
Xiao Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Blue Light ◽  
Umbilical Cord ◽  
Tube Formation ◽  
Human Umbilical Cord ◽  
Light Illumination

Abstract Background The therapeutic potential of mesenchymal stem cells (MSCs) may be attributed partly to the secreted paracrine factors, which comprise exosomes. Exosomes are small, saucer-shaped vesicles containing miRNAs, mRNAs, and proteins. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) have been reported to promote angiogenesis. However, the efficacy of exosome-based therapies is still limited both in vitro and in vivo. The present study aimed to develop a new optical manipulation approach to stimulate the proangiogenic potential of exosomes and characterize its mechanism underlying tissue regeneration. Methods We used blue (455 nm) and red (638 nm) monochromatic light exposure to investigate the processing of stimuli. Exosomes were prepared by QIAGEN exoEasy Maxi kit and confirmed to be present by transmission electron microscopy and immunoblotting analyses. The proangiogenic activity of blue light-treated human umbilical vein endothelial cells (HUVECs), when co-cultured with hUC-MSCs, was assessed by EdU (5-ethynyl-2′-deoxyuridine) incorporation, wound closure, and endothelial tube formation assays. The in vivo angiogenic activity of blue light-treated MSC-derived exosomes (MSC-Exs) was evaluated using both murine matrigel plug and skin wound models. Results We found that 455-nm blue light is effective for promoting proliferation, migration, and tube formation of HUVECs co-cultured with MSCs. Furthermore, MSC-Exs stimulated in vivo angiogenesis and their proangiogenic potential were enhanced significantly upon blue light illumination. Finally, activation of the endothelial cells in response to stimulation by blue light-treated exosomes was demonstrated by upregulation of two miRNAs, miR-135b-5p, and miR-499a-3p. Conclusions Blue (455 nm) light illumination improved the therapeutic effects of hUC-MSC exosomes by enhancing their proangiogenic ability in vitro and in vivo with the upregulation of the following two miRNAs: miR-135b-5p and miR-499a-3p. Graphical abstract

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