A comprehensive cancer-associated microRNA expression profiling and proteomic analysis of human umbilical cord mesenchymal stem cell derived exosomes.

2021 ◽  
Author(s):  
Ganesan Jothimani ◽  
Surajait Pathak ◽  
Suman Dutta ◽  
Asim K. Duttaroy ◽  
Antara Banerjee
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Umbilical Cord ◽  
Expression Patterns ◽  
Functional Enrichment ◽  
Human Umbilical Cord ◽  
Human Mscs ◽  
Anti Cancer

Abstract Background The mesenchymal stem cells (MSCs) have enormous therapeutic potential owing to their multi-lineage differentiation and self-renewal properties. MSCs express growth factors, cytokines, chemokines, and non-coding regulatory RNAs with immunosuppressive, anti-tumor, and migratory properties. MSCs also release several anti-cancer molecules via extracellular vesicles, that act as pro-apoptotic/tumor suppressor factors. This study aimed to identify the stem cell-derived secretome that could exhibit anti-cancer properties through molecular profiling of cargos in MSC-derived exosomes. Methods Human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated from umbilical cord tissues and cultured expanded. After that, exosomes were isolated from the hUCMSC conditioned medium. The miRNA profiling of hUCMSCs and hUCMSC-derived exosomes was performed, followed by functional enrichment analysis. Results The miRNA expression profile and gene ontology (GO) depicts the differential expression patterns of high and less-expressed miRNAs that are delineated to be involved in the regulation of the apoptosis process. The LCMS/MS data and GO analysis indicate that hUCMSC secretomes are involved in several oncogenic and inflammatory signaling cascades. Conclusion Primary human MSCs releases miRNAs and growth factors via exosomes that are increasingly implicated in intercellular communications, and hUCMSC-exosomal miRNAs may have a critical influence in regulating cell death and apoptosis of cancer cells.

scholarly journals A Small-Sized Population of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Shows High Stemness Properties and Therapeutic Benefit

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Miyeon Kim ◽  
Yun Kyung Bae ◽  
Soyoun Um ◽  
Ji Hye Kwon ◽  
Gee-Hye Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Surface Proteins ◽  
Lung Damage ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord

Mesenchymal stem cells (MSCs) represent a promising means to promote tissue regeneration. However, the heterogeneity of MSCs impedes their use for regenerative medicine. Further investigation of this phenotype is required to develop cell therapies with improved clinical efficacy. Here, a small-sized population of human umbilical cord blood-derived MSCs (UCB-MSCs) was isolated using a filter and centrifuge system to analyze its stem cell characteristics. Consequently, this population showed higher cell growth and lower senescence. Additionally, it exhibited diverse stem cell properties including differentiation, stemness, and adhesion, as compared to those of the population before isolation. Using cell surface protein array or sorting analysis, both EGFR and CD49f were identified as markers associated with the small-sized population. Accordingly, suppression of these surface proteins abolished the superior characteristics of this population. Moreover, compared to that with large or nonisolated populations, the small-sized population showed greater therapeutic efficacy by promoting the engraftment potential of infused cells and reducing lung damage in an emphysema mouse model. Therefore, the isolation of this small-sized population of UCB-MSCs could be a simple and effective way to enhance the efficacy of cell therapy.

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.

Human Umbilical Cord Mesenchymal Stem Cells: A New Era for Stem Cell Therapy

2015 ◽  
Vol 24 (3) ◽  
pp. 339-347 ◽  
Author(s):  
Dah-Ching Ding ◽  
Yu-Hsun Chang ◽  
Woei-Cherng Shyu ◽  
Shinn-Zong Lin
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Umbilical Cord ◽  
Stem Cell Therapy ◽  
Human Umbilical Cord ◽  
New Era

scholarly journals Inflammatory Human Umbilical Cord-Derived Mesenchymal Stem Cells Promote Stem Cell-Like Characteristics of Cancer Cells in an IL-1β-Dependent Manner

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Xiaohe Luo ◽  
Shan Huang ◽  
Ningning He ◽  
Chen Liu ◽  
Yanan Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cancer Cells ◽  
Umbilical Cord ◽  
Side Population ◽  
Ovarian Cancer Cells ◽  
Human Umbilical Cord ◽  
Stem Cell Markers ◽  
Dependent Manner

To ensure the safety of clinical applications of MSCs, thorough understanding of their impacts on tumor initiation and progression is essential. Here, to further explore the complex dialog between MSCs and tumor cells, umbilical cord-derived mesenchymal stem cells (UC-MSCs) were employed to be cocultured with either breast or ovarian cancer cells. Though having no obvious influence on proliferation or apoptosis, UC-MSCs exerted intense stem cell-like properties promoting effects on both cancer models. Cocultured cancer cells showed enriched side population, enhanced sphere formation ability, and upregulated pluripotency-associated stem cell markers. Human cytokine array and real-time PCR revealed a panel of MSC-derived prostemness cytokines CCL2, CXCL1, IL-8, and IL-6 which were induced upon coculturing. We further revealed IL-1β, a well-characterized proinflammatory cytokine, to be the inducer of these prostemness cytokines, which was generated from inflammatory UC-MSCs in an autocrine manner. Additionally, with introduction of IL-1RA (an IL-1 receptor antagonist) into the coculturing system, the stem cell-like characteristics promoting effects of inflammatory UC-MSCs were partially blocked. Taken together, these findings suggest that transduced inflammatory MSCs work as a major source of IL-1β in tumor microenvironment and initiate the formation of prostemness niche via regulating their secretome in an IL-1β-dependent manner.

CELLULAR AND MOLECULAR EVALUATION OF IN VITRO QUALITY PARAMETERS OF HUMAN UMBILICAL CORD BLOOD-DERIVED MESENCHYMAL STEM CELLS

2021 ◽  
pp. 52-54
Author(s):  
Sara Jabeen ◽  
Usha Gupta ◽  
Aleem Ahmed Khan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Stem Cell Markers ◽  
Number Of Cells

Introduction: Establishing a reproducible adult stem cell culture system, such as mesenchymal stem cells (MSCs), is critical for elucidating the function of molecular markers associated with these cells' undifferentiated state. In this study, we describe some important parameters to be considered for a successful isolation, culture, and characterization of MSCs from human umbilical cord blood (hUCB). Methods: Five hUCB samples were collected from healthy female subjects who were free from infectious diseases and genetic disorders. Mononuclear cells (MNCs) were counted, and viability was determined using MTT assay. MNCs were cultured in DMEM supplemented with 10% fetal bovine serum and enriched through culture and characterized using morphometric, and molecular analysis. Results: The minimum number of cells was 12.5 million and highest number of cells was 20.6 million from all ve samples. In initial culture of MSCs from hUCB, various morphologic phenotypes were seen, although the cells eventually developed a homogeneous broblast-like shape at day 14 showing >80% conuency. Spindle-shaped clonogenic MSCs expressed a high level of CD90, CD105, and CD73, while negative expression of CD34. Our study provided evidence of expansion of enriched MSCs in culture from day 1 to day 21 as supported by data of CD90, CD105 and CD73 expression levels in a time-dependent manner. Conclusion: Our results suggest that the expanded hUCB harbor an enriched source of MSCs that express pluripotent stem cell markers and lack hematopoietic markers after culture and forms the basis for using hUCB as eminent source of MSCs, which can be used for different therapeutic applications.

scholarly journals Repair of Osteochondral Defects Using Human Umbilical Cord Wharton’s Jelly-Derived Mesenchymal Stem Cells in a Rabbit Model

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Shuyun Liu ◽  
Yanhui Jia ◽  
Mei Yuan ◽  
Weimin Guo ◽  
Jingxiang Huang ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Umbilical Cord ◽  
Wharton’S Jelly ◽  
Cartilage Defects ◽  
Human Umbilical Cord ◽  
Wharton's Jelly

Umbilical cord Wharton’s jelly-derived mesenchymal stem cell (WJMSC) is a new-found mesenchymal stem cell in recent years with multiple lineage potential. Due to its abundant resources, no damage procurement, and lower immunogenicity than other adult MSCs, WJMSC promises to be a good xenogenous cell candidate for tissue engineering. This in vivo pilot study explored the use of human umbilical cord Wharton’s jelly mesenchymal stem cells (hWJMSCs) containing a tissue engineering construct xenotransplant in rabbits to repair full-thickness cartilage defects in the femoral patellar groove. We observed orderly spatial-temporal remodeling of hWJMSCs into cartilage tissues during repair over 16 months, with characteristic architectural features, including a hyaline-like neocartilage layer with good surface regularity, complete integration with adjacent host cartilage, and regenerated subchondral bone. No immune rejection was detected when xenograft hWJMSCs were implanted into rabbit cartilage defects. The repair results using hWJMSCs were superior to those of chondrogenically induced hWJMSCs after assessing gross appearance and histological grading scores. These preliminary results suggest that using novel undifferentiated hWJMSCs as seed cells might be a better approach than using transforming growth factor-β-induced differentiated hWJMSCs for in vivo tissue engineering treatment of cartilage defects. hWJMSC allografts may be promising for clinical applications.

scholarly journals Ex Vivo Expansion of Human Limbal Epithelial Cells Using Human Placenta-Derived and Umbilical Cord-Derived Mesenchymal Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Sang Min Nam ◽  
Yong-Sun Maeng ◽  
Eung Kweon Kim ◽  
Kyoung Yul Seo ◽  
Helen Lew
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Umbilical Cord ◽  
Ex Vivo ◽  
Feeder Cells ◽  
Culture Systems

Ex vivo culture of human limbal epithelial cells (LECs) is used to treat limbal stem cell (LSC) deficiency, a vision loss condition, and suitable culture systems using feeder cells or serum without animal elements have been developed. This study evaluated the use of human umbilical cord or placenta mesenchymal stem cells (C-MSCs or P-MSCs, resp.) as feeder cells in an animal/serum-free coculture system with human LECs. C-/P-MSCs stimulated LEC colony formation of the stem cell markers (p63, ABCG2) and secreted known LEC clonal growth factors (keratinocyte growth factor, β-nerve growth factor). Transforming growth factor-β-induced protein (TGFBIp), an extracellular matrix (ECM) protein, was produced by C-/P-MSCs and resulted in an increase in p63+ ABCG2+ LEC colonies. TGFBIp-activated integrin signaling molecules (FAK, Src, and ERK) were expressed in LECs, and TGFBIp-induced LEC proliferation was effectively blocked by a FAK inhibitor. In conclusion, C-/P-MSCs enhanced LEC culture by increasing growth of the LSC population by secreting growth factors and the ECM protein TGFBIp, which is suggested to be a novel factor for promoting the growth of LECs in culture. C-/P-MSCs may be useful for the generation of animal-free culture systems for the treatment of LSC deficiency.

scholarly journals Human umbilical cord mesenchymal stem cells restore the ovarian metabolome and rescue premature ovarian insufficiency in mice

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yan Zhao ◽  
Jiao Ma ◽  
Peiye Yi ◽  
Jun Wu ◽  
Feiyan Zhao ◽  
...  
Keyword(s):  
Amino Acids ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Umbilical Cord ◽  
Ovarian Function ◽  
Premature Ovarian Insufficiency ◽  
Reproductive Capacity ◽  
Human Umbilical Cord ◽  
Ovarian Insufficiency

Abstract Background Premature ovarian insufficiency (POI) is an ovarian dysfunction that seriously affects a woman’s physiological health and reproduction. Mesenchymal stem cell (MSC) transplantation offers a promising treatment option for ovarian restoration in rodent POI models. However, the efficacy and mechanism of it remain unclear. Methods POI mice model was generated by cyclophosphamide and busulfan, followed with the treatment of tail-vein injection of the human umbilical cord mesenchymal stem cells (hUCMSCs). Maternal physiological changes and offspring behavior were detected. To reveal the pathogenesis and therapeutic mechanisms of POI, we first compared the metabolite profiles of healthy and POI ovarian tissues using untargeted metabolomics analyses. After stem cell therapy, we then collected the ovaries from control, POI, and hUCMSC-treated POI groups for lipid metabolomics and pseudotargeted metabolomics analysis. Results Our results revealed remarkable changes of multiple metabolites, especially lipids, in ovarian tissues after POI generation. Following the transplantation of clinical-grade hUCMSCs, POI mice exhibited significant improvements in body weight, sex hormone levels, estrous cycles, and reproductive capacity. Lipid metabolomics and pseudotargeted metabolomics analyses for the ovaries showed that the metabolite levels in the POI group, mainly lipids, glycerophospholipids, steroids, and amino acids changed significantly compared with the controls’, and most of them returned to near-healthy levels after receiving hUCMSC treatment. Meanwhile, we also observed an increase of monosaccharide levels in the ovaries from POI mice and a decrease after stem cell treatment. Conclusions hUCMSCs restore ovarian function through activating the PI3K pathway by promoting the level of free amino acids, consequently improving lipid metabolism and reducing the concentration of monosaccharides. These findings provide potential targets for the clinical diagnosis and treatment of POI.

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