Displaying publications 341 - 360 of 3311 in total

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  1. Incorporation of Human-Platelet-Derived Growth Factor-BB Encapsulated Poly(lactic-co-glycolic acid) Microspheres into 3D CORAGRAF Enhances Osteogenic Differentiation of Mesenchymal Stromal Cells
    Mohan S, Raghavendran HB, Karunanithi P, Murali MR, Naveen SV, Talebian S, et al.
    ACS Appl Mater Interfaces, 2017 Mar 22;9(11):9291-9303.
    PMID: 28266827 DOI: 10.1021/acsami.6b13422
    Tissue engineering aims to generate or facilitate regrowth or healing of damaged tissues by applying a combination of biomaterials, cells, and bioactive signaling molecules. In this regard, growth factors clearly play important roles in regulating cellular fate. However, uncontrolled release of growth factors has been demonstrated to produce severe side effects on the surrounding tissues. In this study, poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) incorporated three-dimensional (3D) CORAGRAF scaffolds were engineered to achieve controlled release of platelet-derived growth factor-BB (PDGF-BB) for the differentiation of stem cells within the 3D polymer network. Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, scanning electron microscopy, and microtomography were applied to characterize the fabricated scaffolds. In vitro study revealed that the CORAGRAF-PLGA-PDGF-BB scaffold system enhanced the release of PDGF-BB for the regulation of cell behavior. Stromal cell attachment, viability, release of osteogenic differentiation markers such as osteocalcin, and upregulation of osteogenic gene expression exhibited positive response. Overall, the developed scaffold system was noted to support rapid cell expansion and differentiation of stromal cells into osteogenic cells in vitro for bone tissue engineering applications.
    Matched MeSH terms: Cells, Cultured; Mesenchymal Stromal Cells
  2. Microfluidic-Nanofiber Hybrid Array for Screening of Cellular Microenvironments
    Kamei KI, Mashimo Y, Yoshioka M, Tokunaga Y, Fockenberg C, Terada S, et al.
    Small, 2017 05;13(18).
    PMID: 28272774 DOI: 10.1002/smll.201603104
    Cellular microenvironments are generally sophisticated, but crucial for regulating the functions of human pluripotent stem cells (hPSCs). Despite tremendous effort in this field, the correlation between the environmental factors-especially the extracellular matrix and soluble cell factors-and the desired cellular functions remains largely unknown because of the lack of appropriate tools to recapitulate in vivo conditions and/or simultaneously evaluate the interplay of different environment factors. Here, a combinatorial platform is developed with integrated microfluidic channels and nanofibers, associated with a method of high-content single-cell analysis, to study the effects of environmental factors on stem cell phenotype. Particular attention is paid to the dependence of hPSC short-term self-renewal on the density and composition of extracellular matrices and initial cell seeding densities. Thus, this combinatorial approach provides insights into the underlying chemical and physical mechanisms that govern stem cell fate decisions.
    Matched MeSH terms: Embryonic Stem Cells/cytology*
  3. The use of mesenchymal stromal cells in treatment of lung disorders
    Kardia E, Zakaria N, Sarmiza Abdul Halim NS, Widera D, Yahaya BH
    Regen Med, 2017 03;12(2):203-216.
    PMID: 28244823 DOI: 10.2217/rme-2016-0112
    The therapeutic use of mesenchymal stromal cells (MSCs) represents a promising alternative clinical strategy for treating acute and chronic lung disorders. Several preclinical reports demonstrated that MSCs can secrete multiple paracrine factors and that their immunomodulatory properties can support endothelial and epithelial regeneration, modulate the inflammatory cascade and protect lungs from damage. The effects of MSC transplantation into patients suffering from lung diseases should be fully evaluated through careful assessment of safety and associated risks, which is a prerequisite for translation of preclinical research into clinical practice. In this article, we summarize the current status of preclinical research and review initial MSC-based clinical trials for treating lung injuries and lung disorders.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
  4. Impact of Three-Dimentional Culture Systems on Hepatic Differentiation of Puripotent Stem Cells and Beyond
    Ramasamy TS, Ong ALC, Cui W
    Adv Exp Med Biol, 2018 10 26;1077:41-66.
    PMID: 30357683 DOI: 10.1007/978-981-13-0947-2_4
    Generation of functional hepatocytes from human pluripotent stem cells (hPSCs) is a vital tool to produce large amounts of human hepatocytes, which hold a great promise for biomedical and regenerative medicine applications. Despite a tremendous progress in developing the differentiation protocols recapitulating the developmental signalling and stages, these resulting hepatocytes from hPSCs yet achieve maturation and functionality comparable to those primary hepatocytes. The absence of 3D milieu in the culture and differentiation of these hepatocytes may account for this, at least partly, thus developing an optimal 3D culture could be a step forward to achieve this aim. Hence, review focuses on current development of 3D culture systems for hepatic differentiation and maturation and the future perspectives of its application.
    Matched MeSH terms: Pluripotent Stem Cells/cytology*
  5. Comparative efficacy of stem cells and secretome in articular cartilage regeneration: a systematic review and meta-analysis
    Muhammad SA, Nordin N, Mehat MZ, Fakurazi S
    Cell Tissue Res, 2019 Feb;375(2):329-344.
    PMID: 30084022 DOI: 10.1007/s00441-018-2884-0
    Articular cartilage defect remains the most challenging joint disease due to limited intrinsic healing capacity of the cartilage that most often progresses to osteoarthritis. In recent years, stem cell therapy has evolved as therapeutic strategies for articular cartilage regeneration. However, a number of studies have shown that therapeutic efficacy of stem cell transplantation is attributed to multiple secreted factors that modulate the surrounding milieu to evoke reparative processes. This systematic review and meta-analysis aim to evaluate and compare the therapeutic efficacy of stem cell and secretome in articular cartilage regeneration in animal models. We systematically searched the PubMed, CINAHL, Cochrane Library, Ovid Medline and Scopus databases until August 2017 using search terms related to stem cells, cartilage regeneration and animals. A random effect meta-analysis of the included studies was performed to assess the treatment effects on new cartilage formation on an absolute score of 0-100% scale. Subgroup analyses were also performed by sorting studies independently based on similar characteristics. The pooled analysis of 59 studies that utilized stem cells significantly improved new cartilage formation by 25.99% as compared with control. Similarly, the secretome also significantly increased cartilage regeneration by 26.08% in comparison to the control. Subgroup analyses revealed no significant difference in the effect of stem cells in new cartilage formation. However, there was a significant decline in the effect of stem cells in articular cartilage regeneration during long-term follow-up, suggesting that the duration of follow-up is a predictor of new cartilage formation. Secretome has shown a similar effect to stem cells in new cartilage formation. The risk of bias assessment showed poor reporting for most studies thereby limiting the actual risk of bias assessment. The present study suggests that both stem cells and secretome interventions improve cartilage regeneration in animal trials. Graphical abstract ᅟ.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism*
  6. Importance of Stem Cell Migration and Angiogenesis Study for Regenerative Cell-based Therapy: A Review
    Aziz NS, Yusop N, Ahmad A
    Curr Stem Cell Res Ther, 2020;15(3):284-299.
    PMID: 31985383 DOI: 10.2174/1574888X15666200127145923
    Stem cells play an essential role in maintaining homeostasis, as well as participating in new tissue regeneration. Over the past 20 years, a great deal of effort has been made to investigate the behaviour of stem cells to enable their potential use in regenerative medicine. However, a variety of biological characteristics are known to exist among the different types of stem cells due to variations in the methodological approach, formulation of cell culture medium, isolation protocol and cellular niches, as well as species variation. In recent years, cell-based therapy has emerged as one of the advanced techniques applied in both medical and clinical settings. Cell therapies aim to treat and repair the injury sites and replace the loss of tissues by stimulating the repair and regeneration process. In order to enable the use of stem cells in regenerative therapies, further characterisation of cell behaviour, in terms of their proliferation and differentiation capacity, mainly during the quiescent and inductive state is regarded as highly necessary. The central focus of regenerative medicine revolves around the use of human cells, including adult stem cells and induced pluripotent stem cells for cell-based therapy. The purpose of this review was to examine the existing body of literature on stem cell research conducted on cellular angiogenesis and migration, to investigate the validity of different strategies and variations of the cell type used. The information gathered within this review may then be shared with fellow researchers to assist in future research work, engaging in stem cell homing for cell-based therapy to enhance wound healing and tissue regeneration process.
    Matched MeSH terms: Stem Cells/cytology*
  7. Enhanced Degradation of Diesel Oil by Using Biofilms Formed by Indigenous Purple Photosynthetic Bacteria from Oil-Contaminated Coasts of Vietnam on Different Carriers
    Nhi-Cong LT, Lien DT, Gupta BS, Mai CTN, Ha HP, Nguyet NTM, et al.
    Appl Biochem Biotechnol, 2020 May;191(1):313-330.
    PMID: 31853877 DOI: 10.1007/s12010-019-03203-x
    Oil pollution in marine environment caused by oil spillage has been a main threat to the ecosystem including the ocean life and to the human being. In this research, three indigenous purple photosynthetic strains Rhodopseudomonas sp. DD4, DQ41, and FO2 were isolated from oil-contaminated coastal zones in Vietnam. The cells of these strains were immobilized on different carriers including cinder beads (CB), coconut fiber (CF), and polyurethane foam (PUF) for diesel oil removal from artificial seawater. The mixed biofilm formed by using CB, CF, and PUF as immobilization supports degraded 90, 91, and 95% of diesel oil (DO) with the initial concentration of 17.2 g/L, respectively, after 14 days of incubation. The adsorption of DO on different systems was accountable for the removal of 12-16% hydrocarbons for different carriers. To the best of our knowledge, this is the first report on diesel oil degradation by purple photosynthetic bacterial biofilms on different carriers. Moreover, using carriers attaching purple photosynthetic bacteria to remove diesel oil in large scale is considered as an essential method for the improvement of a cost-effective and efficient bioremediation manner. This study can be a promising approach to eliminate DO from oil-contaminated seawater.
    Matched MeSH terms: Cells, Immobilized/physiology*
  8. Fulltext Calpain Inhibition Restores Autophagy and Prevents Mitochondrial Fragmentation in a Human iPSC Model of Diabetic Endotheliopathy
    Ong SB, Lee WH, Shao NY, Ismail NI, Katwadi K, Lim MM, et al.
    Stem Cell Reports, 2019 03 05;12(3):597-610.
    PMID: 30799273 DOI: 10.1016/j.stemcr.2019.01.017
    The relationship between diabetes and endothelial dysfunction remains unclear, particularly the association with pathological activation of calpain, an intracellular cysteine protease. Here, we used human induced pluripotent stem cells-derived endothelial cells (iPSC-ECs) to investigate the effects of diabetes on vascular health. Our results indicate that iPSC-ECs exposed to hyperglycemia had impaired autophagy, increased mitochondria fragmentation, and was associated with increased calpain activity. In addition, hyperglycemic iPSC-ECs had increased susceptibility to cell death when subjected to a secondary insult-simulated ischemia-reperfusion injury (sIRI). Importantly, calpain inhibition restored autophagy and reduced mitochondrial fragmentation, concurrent with maintenance of ATP production, normalized reactive oxygen species levels and reduced susceptibility to sIRI. Using a human iPSC model of diabetic endotheliopathy, we demonstrated that restoration of autophagy and prevention of mitochondrial fragmentation via calpain inhibition improves vascular integrity. Our human iPSC-EC model thus represents a valuable platform to explore biological mechanisms and new treatments for diabetes-induced endothelial dysfunction.
    Matched MeSH terms: Endothelial Cells; Induced Pluripotent Stem Cells
  9. Experimental larval infestation of zebu cattle and its crosses: effect of antihistamine alone or in combination with dexamethasone treatment on the engorgement and oviposition on tick feeding lesion
    Abdulla MA, Khairul Anuar A, Khalifa S, Salmah I, Mohamad Nazmul HM, Suzainur KAR, et al.
    JUMMEC, 2002;7:135-141.
    Four calves from each group of purebred Kedah kelantan (KK), halfbred KK X Friesian, and quarterbred KK X Friesian were experimentally infested with Boophilus micropills larvae. Two calves from each genotype were injected, intramuscularly with antihistamine while the remaining two animals in each genotype received the same dose of antihistamine and dexamethasone. Dexamethasone combined anti-histamine treatment suppress tick resistance as manifested by the production of higher number of engorged female ticks, higher mean weight of replete ticks, mean weight of eggs and mean number of larvae hatched from 1 g of eggs. In anti-histamine treated animals there was no reduction of resistant in all animals as manifested by a few ticks were able to feed successfully. At 1, 2, and 3 hours post-larval attachment in anti-histamine and dexamethasone treated cattle there was complete ablation of the cellular infiltration in the dermis beneath the tick mouthparts, especially eosinophil and basophils. There was little destruction of tissue. However, in anti-histamine treated cattle there were more cellular infiltration and degranulation in the dermis. The cells infiltrating the dermis were mainly eosinophils followed by neutrophs, mast cells and basophils and some of these cells showed sign of degranulation. At 24 hours postlarval attachment, animals lTeated with anti-histamine and dexamethasone showed reduction of, cellular infiltration, degranulation, size of the epidermal lesion and tissue damage. The neutrophils were the predominant cells within the epidermal lesions. However, animals in anti-histamine treatment showed edema, more cellular infiltration and degranulation, and destruction of tissues as compared to antihistamine and dexamethasone treated animals. In anti-histamine treated cattle the epidermal lesions were obviously larger and the percentage of eosinophils and basophils were higher than those of antihistamine and dexamethasone treated animals. KEYWORDS: Kedah-Kelantan cattle, KK X Friesian callie, B. micropflls, dexamethasone, antihistamine, cellular response.
    Matched MeSH terms: Cells; Mast Cells
  10. A Concise Review on Mesenchymal Stem Cells for Tissue Engineering with a Perspective on Ocular Surface Regeneration
    Salih M, Shaharuddin B, Abdelrazeg S
    Curr Stem Cell Res Ther, 2020;15(3):211-218.
    PMID: 31995019 DOI: 10.2174/1574888X15666200129145251
    Organ and tissue transplantation are limited by the scarcity of donated organs or tissue sources. The success of transplantation is limited by the risk of disease transmission and immunological- related rejection. There is a need for new strategies and innovative solutions to make transplantation readily available, safer and with less complications to increase the success rates. Accelerating progress in stem cell biology and biomaterials development have pushed tissue and organ engineering to a higher level. Among stem cells repertoire, Mesenchymal Stem Cells (MSC) are gaining interest and recognized as a cell population of choice. There is accumulating evidence that MSC growth factors, its soluble and insoluble proteins are involved in several key signaling pathways to promote tissue development, cellular differentiation and regeneration. MSC as multipotent non-hematopoietic cells with paracrine factors is advantageous for regenerative therapies. In this review, we discussed and summarized the important features of MSC including its immunomodulatory properties, mechanism of homing in the direction of tissue injury, licensing of MSC and the role of MSC soluble factors in cell-free therapy. Special consideration is highlighted on the rapidly growing research interest on the roles of MSC in ocular surface regeneration.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
  11. Mobilized Peripheral Blood Stem Cells are Pluripotent and Can Be Safely Harvested and Stored for Cartilage Repair
    Anz AW, Torres J, Plummer HA, Siew-Yoke Jee C, Dekker TJ, Johnson KB, et al.
    Arthroscopy, 2021 11;37(11):3347-3356.
    PMID: 33940122 DOI: 10.1016/j.arthro.2021.04.036
    PURPOSE: The primary objective of this study was to reproduce and validate the harvest, processing and storage of peripheral blood stem cells for a subsequent cartilage repair trial, evaluating safety, reliability, and potential to produce viable, sterile stem cells.

    METHODS: Ten healthy subjects (aged 19-44 years) received 3 consecutive daily doses of filgrastim followed by an apheresis harvest of mononuclear cells on a fourth day. In a clean room, the apheresis product was prepared for cryopreservation and processed into 4 mL aliquots. Sterility and qualification testing were performed pre-processing and post-processing at multiple time points out to 2 years. Eight samples were shipped internationally to validate cell transport potential. One sample from all participants was cultured to test proliferative potential with colony forming unit (CFU) assay. Five samples, from 5 participants were tested for differentiation potential, including chondrogenic, adipogenic, osteogenic, endoderm, and ectoderm assays.

    RESULTS: Fresh aliquots contained an average of 532.9 ± 166. × 106 total viable cells/4 mL vial and 2.1 ± 1.0 × 106 CD34+ cells/4 mL vial. After processing for cryopreservation, the average cell count decreased to 331.3 ± 79. × 106 total viable cells /4 mL vial and 1.5 ± 0.7 × 106 CD34+ cells/4 mL vial CD34+ cells. Preprocessing viability averaged 99% and postprocessing 88%. Viability remained constant after cryopreservation at all subsequent time points. All sterility testing was negative. All samples showed proliferative potential, with average CFU count 301.4 ± 63.9. All samples were pluripotent.

    CONCLUSIONS: Peripheral blood stem cells are pluripotent and can be safely harvested/stored with filgrastim, apheresis, clean-room processing, and cryopreservation. These cells can be stored for 2 years and shipped without loss of viability.

    CLINICAL RELEVANCE: This method represents an accessible stem cell therapy in development to augment cartilage repair.

    Matched MeSH terms: Peripheral Blood Stem Cells*
  12. Cytotoxicity and electron microscopy of cell death induced by goniothalamin
    Ali AM, Mackeen MM, Hamid M, Aun QB, Zauyah Y, Azimahtol HL, et al.
    Planta Med, 1997 Feb;63(1):81-3.
    PMID: 9063100
    The cytotoxicity of goniothalamin was found to be strong towards both cancerous (HGC-27, MCF-7, PANC-1, HeLa), and non-cancerous (3T3) cell lines, especially in cases of dividing cells. Drug exposure studies indicated that the cytotoxic action of goniothalamin was time- and dose-dependent. At the ultrastructural level, goniothalamin-induced cytotoxicity revealed a necrotic mode of cell death towards MCF-7 cells.
    Matched MeSH terms: Tumor Cells, Cultured; 3T3 Cells
  13. The potential role of mesenchymal stem cells in modulating antiageing process
    Govindasamy V, Rajendran A, Lee ZX, Ooi GC, Then KY, Then KL, et al.
    Cell Biol Int, 2021 Oct;45(10):1999-2016.
    PMID: 34245637 DOI: 10.1002/cbin.11652
    Ageing and age-related diseases share some basic origin that largely converges on inflammation. Precisely, it boils down to a common pathway characterised by the appearance of a fair amount of proinflammatory cytokines known as inflammageing. Among the proposed treatment for antiageing, MSCs gained attention in recent years. Since mesenchymal stem cells (MSCs) can differentiate itself into a myriad of terminal cells, previously it was believed that these cells migrate to the site of injury and perform their therapeutic effect. However, with the more recent discovery of huge amounts of paracrine factors secreted by MSCs, it is now widely accepted that these cells do not engraft upon transplantation but rather unveil their benefits through excretion of bioactive molecules namely those involved in inflammatory and immunomodulatory activities. Conversely, the true function of these paracrine changes has not been thoroughly investigated all these years. Hence, this review will describe in detail on ways MSCs may capitalize its paracrine properties in modulating antiageing process. Through a comprehensive literature search various elements in the antiageing process, we aim to provide a novel treatment perspective of MSCs in antiageing related clinical conditions.
    Matched MeSH terms: Hematopoietic Stem Cells/cytology*
  14. Homeobox genes and tooth development: Understanding the biological pathways and applications in regenerative dental science
    Ramanathan A, Srijaya TC, Sukumaran P, Zain RB, Abu Kasim NH
    Arch Oral Biol, 2018 Jan;85:23-39.
    PMID: 29031235 DOI: 10.1016/j.archoralbio.2017.09.033
    OBJECTIVES: Homeobox genes are a group of conserved class of transcription factors that function as key regulators during the embryonic developmental processes. They act as master regulator for developmental genes, which involves coordinated actions of various auto and cross-regulatory mechanisms. In this review, we summarize the expression pattern of homeobox genes in relation to the tooth development and various signaling pathways or molecules contributing to the specific actions of these genes in the regulation of odontogenesis.

    MATERIALS AND METHODS: An electronic search was undertaken using combination of keywords e.g. Homeobox genes, tooth development, dental diseases, stem cells, induced pluripotent stem cells, gene control region was used as search terms in PubMed and Web of Science and relevant full text articles and abstract were retrieved that were written in English. A manual hand search in text books were also carried out. Articles related to homeobox genes in dentistry and tissue engineering and regenerative medicine of odontogenesis were selected.

    RESULTS: The possible perspective of stem cells technology in odontogenesis and subsequent analysis of gene correction pertaining to dental disorders through the possibility of induced pluripotent stem cells technology is also inferred.

    CONCLUSIONS: We demonstrate the promising role of tissue engineering and regenerative medicine on odontogenesis, which can generate a new ray of hope in the field of dental science.

    Matched MeSH terms: Stem Cells/physiology*
  15. Fulltext IL-4 enhances IL-10 production in Th1 cells: implications for Th1 and Th2 regulation
    Mitchell RE, Hassan M, Burton BR, Britton G, Hill EV, Verhagen J, et al.
    Sci Rep, 2017 Sep 12;7(1):11315.
    PMID: 28900244 DOI: 10.1038/s41598-017-11803-y
    IL-10 is an immunomodulatory cytokine with a critical role in limiting inflammation in immune-mediated pathologies. The mechanisms leading to IL-10 expression by CD4(+) T cells are being elucidated, with several cytokines implicated. We explored the effect of IL-4 on the natural phenomenon of IL-10 production by a chronically stimulated antigen-specific population of differentiated Th1 cells. In vitro, IL-4 blockade inhibited while addition of exogenous IL-4 to Th1 cultures enhanced IL-10 production. In the in vivo setting of peptide immunotherapy leading to a chronically stimulated Th1 phenotype, lack of IL-4Rα inhibited the induction of IL-10. Exploring the interplay of Th1 and Th2 cells through co-culture, Th2-derived IL-4 promoted IL-10 expression by Th1 cultures, reducing their pathogenicity in vivo. Co-culture led to upregulated c-Maf expression with no decrease in the proportion of T-bet(+) cells in these cultures. Addition of IL-4 also reduced the encephalitogenic capacity of Th1 cultures. These data demonstrate that IL-4 contributes to IL-10 production and that Th2 cells modulate Th1 cultures towards a self-regulatory phenotype, contributing to the cross-regulation of Th1 and Th2 cells. These findings are important in the context of Th1 driven diseases since they reveal how the Th1 phenotype and function can be modulated by IL-4.
    Matched MeSH terms: Th1 Cells; Th2 Cells
  16. Fulltext Synthesis and In Vitro Cytotoxicity of the 4-(Halogenoanilino)-6-bromoquinazolines and Their 6-(4-Fluorophenyl) Substituted Derivatives as Potential Inhibitors of Epidermal Growth Factor Receptor Tyrosine Kinase
    Mphahlele MJ, Paumo HK, Choong YS
    Pharmaceuticals (Basel), 2017 Nov 20;10(4).
    PMID: 29156606 DOI: 10.3390/ph10040087
    Series of the 2-unsubstituted and 2-(4-chlorophenyl)-substituted 4-anilino-6-bromoquinazolines and their 6-(4-fluorophenyl)-substituted derivatives were evaluated for in vitro cytotoxicity against MCF-7 and HeLa cells. The 2-unsubstituted 4-anilino-6-bromoquinazolines lacked activity, whereas most of their 2-(4-chlorophenyl) substituted derivatives were found to exhibit significant cytotoxicity and selectivity against HeLa cells. Replacement of bromine with 4-fluorophenyl group for the 2-unsubstituted 4-anilinoquinazolines resulted in superior activity against HeLa cells compared to Gefitinib. The presence of a 4-fluorophenyl group in the 2-(4-chlorophenyl) substituted derivatives led to increased cytotoxicity against HeLa cells, except for the 3-chloroanilino derivative. The most active compounds, namely, 3g, 3l, and 4l, were found to exhibit a moderate to significant inhibitory effect against epidermal growth factor receptor tyrosine kinase (EGFR-TK). The EGFR molecular docking model suggested that these compounds are nicely bound to the region of EGFR.
    Matched MeSH terms: HeLa Cells; MCF-7 Cells
  17. Biosafety and bioefficacy assessment of human mesenchymal stem cells: what do we know so far?
    Yong KW, Choi JR, Dolbashid AS, Wan Safwani WKZ
    Regen Med, 2018 03;13(2):219-232.
    PMID: 29509072 DOI: 10.2217/rme-2017-0078
    An outstanding amount of resources has been used in research on manipulation of human stem cells, especially mesenchymal stem cells (MSCs), for various clinical applications. However, human MSCs have not been fully utilized in clinical applications due to restrictions with regard to their certain biosafety and bioefficacy concerns, for example, genetic abnormality, tumor formation, induction of host immune response and failure of homing and engraftment. This review summarizes the biosafety and bioefficacy assessment of human MSCs in terms of genetic stability, tumorigenicity, immunogenicity, homing and engraftment. The strategies used to reduce the biosafety concerns and improve the bioefficacy of human MSCs are highlighted. In addition, the approaches that can be implemented to improve their biosafety and bioefficacy assessment are briefly discussed.
    Matched MeSH terms: Mesenchymal Stromal Cells*
  18. Improved Anticancer Effect of Magnetite Nanocomposite Formulation of GALLIC Acid (Fe₃O₄-PEG-GA) Against Lung, Breast and Colon Cancer Cells
    Rosman R, Saifullah B, Maniam S, Dorniani D, Hussein MZ, Fakurazi S
    Nanomaterials (Basel), 2018 Feb 02;8(2).
    PMID: 29393902 DOI: 10.3390/nano8020083
    Lung cancer, breast cancer and colorectal cancer are the most prevalent fatal types of cancers globally. Gallic acid (3,4,5-trihydroxybenzoic acid) is a bioactive compound found in plants and foods, such as white tea, witch hazel and it has been reported to possess anticancer, antioxidant and anti-inflammatory properties. In this study we have redesigned our previously reported anticancer nanocomposite formulation with improved drug loading based on iron oxide magnetite nanoparticles coated with polyethylene glycol and loaded with anticancer drug gallic acid (Fe₃O₄-PEG-GA). The in vitro release profile and percentage drug loading were found to be better than our previously reported formulation. The anticancer activity of pure gallic acid (GA), empty carrier (Fe₃O₄-PEG) nanocarrier and of anticancer nanocomposite (Fe₃O₄-PEG-GA) were screened against human lung cancer cells (A549), human breast cancer cells (MCF-7), human colon cancer cells (HT-29) and normal fibroblast cells (3T3) after incubation of 24, 48 and 72 h using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. The designed formulation (Fe₃O₄-PEG-GA) showed better anticancer activity than free gallic acid (GA). The results of the in vitro studies are highly encouraging to conduct the in vivo studies.
    Matched MeSH terms: HT29 Cells; MCF-7 Cells
  19. Fulltext IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection
    Han F, Gulam MY, Zheng Y, Zulhaimi NS, Sia WR, He D, et al.
    Front Immunol, 2022;13:985385.
    PMID: 36341446 DOI: 10.3389/fimmu.2022.985385
    MAIT cells are persistently depleted and functionally exhausted in HIV-1-infected patients despite long-term combination antiretroviral therapy (cART). IL-7 treatment supports MAIT cell reconstitution in vivo HIV-1-infected individuals and rescues their functionality in vitro. Single-nucleotide polymorphisms (SNPs) of the IL-7RA gene modulate the levels of soluble(s)IL-7Rα (sCD127) levels and influence bioavailability of circulating IL-7. Here we evaluate the potential influence of IL-7RA polymorphisms on MAIT cell numbers and function in healthy control (HC) subjects and HIV-1-infected individuals on long-term cART. Our findings indicate that IL-7RA haplotype 2 (H2*T), defined as T-allele carriers at the tagging SNP rs6897932, affects the size of the peripheral blood MAIT cell pool, as well as their production of cytokines and cytolytic effector proteins in response to bacterial stimulation. H2*T carriers had lower sIL-7Rα levels and higher MAIT cell frequency with enhanced functionality linked to higher expression of MAIT cell-associated transcription factors. Despite an average of 7 years on suppressive cART, MAIT cell levels and function in HIV-1-infected individuals were still significantly lower than those of HC. Notably, we observed a significant correlation between MAIT cell levels and cART duration only in HIV-1-infected individuals carrying IL-7RA haplotype 2. Interestingly, treatment with sIL-7Rα in vitro suppressed IL-7-dependent MAIT cell proliferation and function following cognate stimulations. These observations suggest that sIL-7Rα levels may influence MAIT cell numbers and function in vivo by limiting IL-7 bioavailability to MAIT cells. Collectively, these observations suggest that IL-7RA polymorphisms may play a significant role in MAIT cell biology and influence MAIT cells recovery in HIV-1 infection. The potential links between IL7RA polymorphisms, MAIT cell immunobiology, and HIV-1 infection warrant further studies going forward.
    Matched MeSH terms: Mucosal-Associated Invariant T Cells*
  20. Fulltext Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface
    Zhang S, Chong LH, Woon JYX, Chua TX, Cheruba E, Yip AK, et al.
    Commun Biol, 2023 Jan 18;6(1):62.
    PMID: 36653484 DOI: 10.1038/s42003-023-04421-0
    Biochemical signaling and mechano-transduction are both critical in regulating stem cell fate. How crosstalk between mechanical and biochemical cues influences embryonic development, however, is not extensively investigated. Using a comparative study of focal adhesion constituents between mouse embryonic stem cell (mESC) and their differentiated counterparts, we find while zyxin is lowly expressed in mESCs, its levels increase dramatically during early differentiation. Interestingly, overexpression of zyxin in mESCs suppresses Oct4 and Nanog. Using an integrative biochemical and biophysical approach, we demonstrate involvement of zyxin in regulating pluripotency through actin stress fibres and focal adhesions which are known to modulate cellular traction stress and facilitate substrate rigidity-sensing. YAP signaling is identified as an important biochemical effector of zyxin-induced mechanotransduction. These results provide insights into the role of zyxin in the integration of mechanical and biochemical cues for the regulation of embryonic stem cell fate.
    Matched MeSH terms: Embryonic Stem Cells/metabolism
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