scholarly journals Cell-to-Cell Culture Inhibits Dedifferentiation of Chondrocytes and Induces Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Xingfu Li ◽  
Yujie Liang ◽  
Xiao Xu ◽  
Jianyi Xiong ◽  
Kan Ouyang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Cartilage Damage ◽  
Great Promise ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Contact ◽  
Human Umbilical Cord ◽  
Low Density ◽  
Cell Based Therapy

Background. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) possess great promise as a therapeutic to repair damaged cartilage. Direct intra-articular injection of mesenchymal stem cells has been shown to reduce cartilage damage and is advantageous as surgical implantation and associated side effects can be avoided using this approach. However, the efficacy of stem cell-based therapy for cartilage repair depends highly on the direct interactions of these stem cells with chondrocytes in the joint. In this study, we have carried out an in vitro cell-to-cell contact coculture study with human articular chondrocytes (hACs) and hUC-MSCs, with the goal of this study being to evaluate interactions between hACs and hUC-MSCs. Methods. Low-density monolayer cultures of hUC-MSCs and hACs were mixed at a ratio of 1 : 1 in direct cell-to-cell contact groups. Results were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. Results. A mixed coculture of hUC-MSCs and hACs was found to exhibit synergistic interactions with enhanced differentiation of hUC-MSCs and reduced dedifferentiation of chondrocytes. Mixed cultures after 21 days were found to exhibit sufficient chondrogenic induction. Conclusions. The results from this study suggest the presence of mutual effects between hUC-MSCs and hACs even culture at low density and provide further support for the use of intra-articular injection strategies for cartilage defect treatment.

Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy

2015 ◽  
Vol 15 (9) ◽  
pp. 1293-1306 ◽  
Author(s):  
Tan Li ◽  
Mingxu Xia ◽  
Yuanyuan Gao ◽  
Yanting Chen ◽  
Yun Xu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Human Umbilical Cord ◽  
Cell Based Therapy

scholarly journals Human Umbilical Cord Mesenchymal Stem Cells Inhibit the Function of Allogeneic Activated Vγ9Vδ2 T Lymphocytes In Vitro

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaohuan Liu ◽  
Ting Feng ◽  
Tianxiang Gong ◽  
Chongyang Shen ◽  
Tingting Zhu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Umbilical Cord ◽  
Interleukin 2 ◽  
Cell Contact ◽  
Human Umbilical Cord ◽  
Fas L

Background. Human umbilical cord mesenchymal stem cells (UC-MSCs) can regulate the function of immune cells. However, whether and how UC-MSCs can modulate the function of Vγ9Vδ2 T cells has not been fully understood. Methods. The PBMCs or Vγ9Vδ2 T cells were activated and expanded with pamidronate (PAM) and interleukin-2 (IL-2) with or without the presence UC-MSCs. The effects of UC-MSCs on the proliferation, cytokine expression, and cytotoxicity of Vγ9Vδ2 T cells were determined by flow cytometry. The effects of UC-MSCs on Fas-L, TRAIL-expressing Vγ9Vδ2 T cells, and Vγ9Vδ2 T cell apoptosis were determined by flow cytometry. Results. UC-MSCs inhibited Vγ9Vδ2 T cell proliferation in a dose-dependent but cell-contact independent manner. Coculture with UC-MSCs reduced the frequency of IFNγ+ but increased granzyme B+ Vγ9Vδ2 T cells. UC-MSCs inhibited the cytotoxicity of Vγ9Vδ2 T cells against influenza virus H1N1 infected A549 cells and also reduced the frequency of Fas-L+, TRAIL+ Vγ9Vδ2 T cells but failed to modulate the apoptosis of Vγ9Vδ2 T cells. Conclusions. These results indicated that UC-MSCs efficiently suppressed the proliferation and cytotoxicity of Vγ9Vδ2 T cells and modulated their cytokine production. Fas-L and TRAIL were involved in the regulation. Cell contact and apoptosis of Vγ9Vδ2 T cells were not necessary for the inhibition.

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 Immortalization of Human Fetal Cells: The Life Span of Umbilical Cord Blood-derived Cells Can Be Prolonged without Manipulating p16INK4a/RB Braking Pathway

2005 ◽  
Vol 16 (3) ◽  
pp. 1491-1499 ◽  
Author(s):  
Masanori Terai ◽  
Taro Uyama ◽  
Tadashi Sugiki ◽  
Xiao-Kang Li ◽  
Akihiro Umezawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Life Span ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Future Application ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Cell Based Therapy

Human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) are expected to serve as an excellent alternative to bone marrow-derived human mesenchymal stem cells. However, it is difficult to study them because of their limited life span. To overcome this problem, we attempted to produce a strain of UCBMSCs with a long life span and to investigate whether the strain could maintain phenotypes in vitro. UCBMSCs were infected with retrovirus carrying the human telomerase reverse transcriptase (hTERT) to prolong their life span. The UCBMSCs underwent 30 population doublings (PDs) and stopped dividing at PD 37. The UCBMSCs newly established with hTERT (UCBTERTs) proliferated for >120 PDs. The p16INK4a/RB braking pathway leading to senescence can be inhibited by introduction of Bmi-1, a polycomb-group gene, and human papillomavirus type 16 E7, but the extension of the life span of the UCBMSCs with hTERT did not require inhibition of the p16INK4a/RB pathway. The characteristics of the UCBTERTs remained unchanged during the prolongation of life span. UCBTERTs provide a powerful model for further study of cellular senescence and for future application to cell-based therapy by using umbilical cord blood cells.

scholarly journals Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Contribute to Chondrogenesis in Coculture with Chondrocytes

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Xingfu Li ◽  
Li Duan ◽  
Yujie Liang ◽  
Weimin Zhu ◽  
Jianyi Xiong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Protein Expression ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Type I ◽  
Low Density

Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have been shown as the most potential stem cell source for articular cartilage repair. In this study, we aimed to develop a method for long-term coculture of human articular chondrocytes (hACs) and hUCB-MSCs at low density in vitro to determine if the low density of hACs could enhance the hUCB-MSC chondrogenic differentiation as well as to determine the optimal ratio of the two cell types. Also, we compared the difference between direct coculture and indirect coculture at low density. Monolayer cultures of hUCB-MSCs and hACs were investigated at different ratios, at direct cell-cell contact groups for 21 days. Compared to direct coculture, hUCB-MSCs and hACs indirect contact culture significantly increased type II collagen (COL2) and decreased type I collagen (COL1) protein expression levels. SRY-box 9 (SOX9) mRNA levels and protein expression were highest in indirect coculture. Overall, these results indicate that low density direct coculture induces fibrocartilage. However, indirect coculture in conditioned chondrocyte cell culture medium can increase expression of chondrogenic markers and induce hUCB-MSCs differentiation into mature chondrocytes. This work demonstrates that it is possible to promote chondrogenesis of hUCB-MSCs in combination with hACs, further supporting the concept of novel coculture strategies for tissue engineering.

Effects of human umbilical cord mesenchymal stem cells on inflammatory factors and miR-181a in T lymphocytes from patients with systemic lupus erythematosus

Lupus ◽  
2019 ◽  
Vol 29 (2) ◽  
pp. 126-135
Author(s):  
B Zheng ◽  
P Zhang ◽  
L Yuan ◽  
R K Chhetri ◽  
Y Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Lymphocytes ◽  
Umbilical Cord ◽  
Lupus Erythematosus ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Umbilical Cord ◽  
Expression Levels ◽  
Gene And Protein Expression

Objectives The present study aimed to explore the effect of umbilical cord mesenchymal stem cells (UC-MSCs) on the modulation of T lymphocytes from system lupus erythematosus (SLE) patients and the possible mechanism. Methods A total of 24 hospitalized SLE patients and 28 healthy individuals were enrolled. T lymphocytes were sorted using Miltenyi magnetic beads. After the addition of recombinant human interleukin (IL)-2 and CD3CD28 T-cell activator, cells were loaded onto six-well plates pre-inoculated or not with UC-MSCs for 1 week of culture. The supernatants were collected for testing inflammatory factors by enzyme-linked immunosorbent assay. Meanwhile, T lymphocytes were collected to assess the expression levels of genes, proteins in relation to SLE and miR-181a by polymerase chain reaction and Western blot. Results Compared with T lymphocytes cultured alone, interferon-γ, IL-4, IL-6 and IL-10 levels were significantly decreased in T lymphocytes from SLE patients co-cultured with UC-MSCs. In addition, the gene and protein expression levels of TNF alpha, osteopontin and nuclear factor-kappa B in T lymphocytes were significantly decreased, while miR-181a expression was markedly elevated ( p < 0.05 or 0.008). Conclusion UC-MSCs have showed certain immunomodulatory and inhibitory effects in vitro on T lymphocytes from SLE patients, which could potentially be a beneficial treatment of the disease. UC-MSCs may up-regulate miR-181a and down-regulate inflammation-related gene expression.

scholarly journals Side-by-Side Comparison of the Biological Characteristics of Human Umbilical Cord and Adipose Tissue-Derived Mesenchymal Stem Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Li Hu ◽  
Jingqiong Hu ◽  
Jiajia Zhao ◽  
Jiarong Liu ◽  
Weixiang Ouyang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Umbilical Cord ◽  
Human Adipose Tissue ◽  
Cell Types ◽  
Human Umbilical Cord ◽  
Cell Based Therapy ◽  
Secretion Profile ◽  
Immunological Phenotype

Both human adipose tissue-derived mesenchymal stem cells (ASCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs) have been explored as attractive mesenchymal stem cells (MSCs) sources, but very few parallel comparative studies of these two cell types have been made. We designed a side-by-side comparative study by isolating MSCs from the adipose tissue and umbilical cords from mothers delivering full-term babies and thus compared the various biological aspects of ASCs and UC-MSCs derived from the same individual, in one study. Both types of cells expressed cell surface markers characteristic of MSCs. ASCs and UC-MSCs both could be efficiently induced into adipocytes, osteoblasts, and neuronal phenotypes. While there were no significant differences in their osteogenic differentiation, the adipogenesis of ASCs was more prominent and efficient than UC-MSCs. In the meanwhile, ASCs responded better to neuronal induction methods, exhibiting the higher differentiation rate in a relatively shorter time. In addition, UC-MSCs exhibited a more prominent secretion profile of cytokines than ASCs. These results indicate that although ASCs and UC-MSCs share considerable similarities in their immunological phenotype and pluripotentiality, certain biological differences do exist, which might have different implications for future cell-based therapy.

scholarly journals Human umbilical cord mesenchymal stem cells deliver exogenous miR-26a-5p via exosomes to inhibit nucleus pulposus cell pyroptosis through METTL14/NLRP3

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Xiaoqiu Yuan ◽  
Tiefeng Li ◽  
Lei Shi ◽  
Jinhao Miao ◽  
Yongfei Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Mesenchymal Stem Cells ◽  
Nucleus Pulposus ◽  
Umbilical Cord ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Umbilical Cord ◽  
Dependent Manner ◽  
Western Blots

Abstract Background Intervertebral disc degeneration (IVDD) is the breakdown of the discs supporting the vertebrae. It is one of the most frequent causes of back pain worldwide. Currently, the clinical interventions for IVDD are mainly focused on symptom releases. Thus, new therapeutic options are needed. Methods Nucleus pulposus (NP) samples were obtained from 20 patients experiencing IVDD and 10 healthy volunteers compared for mRNA N6-methyladenosine (m6A) mRNA modification as well as methyltransferase (METT) like METTL3, METTL14, and Wilms’ tumor 1-associated protein mRNA and protein abundance following exosomes exposure from mesenchymal stem cells. In addition, microRNA expressions were also compared. The correlation between the NLR family pyrin domain containing 3 (NLRP3) and METTL14 was measured by luciferase reporter assay. Cytokines were evaluated using an enzyme-linked immunosorbent assay. METTL14, NLRP3, and insulin-like growth factor 2 mRNA-binding protein 2 mRNAs were measured via a quantitative reverse transcription-polymerase chain reaction. Protein was assayed using western blots. Cell death was assessed by propidium iodide staining, lactate dehydrogenase release, gasdermin-N domain abundance, and caspase-1 activation. Results The human umbilical cord mesenchymal stem cell (hucMSC) exosomes were found to effectively improve the viability of NP cells and protect them from pyroptosis through targeting METTL14, with a methyltransferase catalyzing m6A modification. METTL14 was highly present in NP cells from IVDD patients, which stabilize NLRP3 mRNA in an IGFBP2-dependent manner. The elevated NLRP3 levels result in the increase of interleukin 1β (IL-1β) and IL-18 levels and trigger pyroptotic NP cell death. Such pathogenic axis could be blocked by hucMSC exosomes, which directly degrade METTL14 through exosomal miR-26a-5p. Conclusions The results of the current study revealed the beneficial effects of hucMSC exosomes on NP cells and determined a potential mechanism inducing IVDD.

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