Displaying publications 1 - 20 of 77 in total

  1. Taher M, Abdul Majid FA, Sarmidi MR
    Med J Malaysia, 2004 May;59 Suppl B:97-8.
    PMID: 15468836
    In attempt to discover a small active compound that could promote adipogenesis, we investigated the ability of cinnamon (Cinnamomum zeylanicum) extracts to stimulate 3T3-L1 preadipocytes, In this study, we designed an experiment by replacing insulin with cinnamon extracts. The differentiated of 3T3-L1 adipocytes were monitored using oil red O staining method. Induction of adipocyte formation by cinnamtannin B1 or water extract gave the similar effects to insulin activity in adipogenesis.
    Matched MeSH terms: Cell Differentiation/drug effects*
  2. Susanti D, Amiroudine MZ, Rezali MF, Taher M
    Nat Prod Res, 2013 Mar;27(4-5):417-24.
    PMID: 22988818 DOI: 10.1080/14786419.2012.725399
    Friedelin and lanosterol have been isolated from twigs of Garcinia prainiana. Their structures were elucidated by spectroscopic methods. The compounds were examined for their effects on 3T3-L1 adipocytes. In the MTT assay, it was found that the compounds had no cytotoxic effects up to 25 µM. Adipocyte differentiation analysis was carried out by Oil Red O staining method. In the presence of adipogenic cocktail (MDI), it was found that friedelin and lanosterol enhanced intracellular fat accumulation by 2.02 and 2.18-fold, respectively, compared with the vehicle-treated cells. Deoxyglucose uptake assay was used to examine the insulin sensitivity of adipocytes in the presence of the compounds. It was found that friedelin was able to stimulate glucose uptake up to 1.8-fold compared with insulin-treated cells. It was suggested that friedelin and lanosterol may be beneficial to mimic insulin action that would be useful in the treatment of diabetes type 2 patients.
    Matched MeSH terms: Cell Differentiation/drug effects
  3. Ubaidah MA, Chua KH, Ami M, Zainal A, Saim A, Saim L, et al.
    J Int Adv Otol, 2015 Apr;11(1):23-9.
    PMID: 26223713 DOI: 10.5152/iao.2015.539
    Loss of auditory hair cells is a major cause of deafness. The presence of auditory progenitor cells in the inner ear raises the hope for mammalian inner ear cell regeneration. In this study, we aimed to investigate the effect of growth factor supplementations, namely a combination of epidermal growth factor (EGF), insulin-like growth factor (IGF), and beta (β)-fibroblast growth factor (βFGF), on the expression of hair cell-specific markers by cells harvested from the cochlear membrane. This would provide an insight into the capability of these cells to differentiate into hair cells.
    Matched MeSH terms: Cell Differentiation/drug effects
  4. Moshiri A, Sharifi AM, Oryan A
    Clin Exp Pharmacol Physiol, 2016 Jul;43(7):659-84.
    PMID: 27061579 DOI: 10.1111/1440-1681.12577
    Simvastatin is a lipid lowering drug whose beneficial role on bone metabolism was discovered in 1999. Several in vivo studies evaluated its role on osteoporosis and fracture healing, however, controversial results are seen in the literature. For this reason, Simvastatin has not been the focus of any clinical trials as yet. This systematic review clears the mechanisms of action of Simvastatin on bone metabolism and focuses on in vivo investigations that have evaluated its role on osteoporosis and fracture repair to find out (i) whether Simvastatin is effective on treatment of osteoporosis and fracture repair, and (ii) which of the many available protocols may have the ability to be translated in the clinical setting. Simvastatin induces osteoinduction by increasing osteoblast activity and differentiation and inhibiting their apoptosis. It also reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts and their differentiation. Controversial results between the in vivo studies are mostly due to the differences in the route of administration, dose, dosage and carrier type. Local delivery of Simvastatin through controlled drug delivery systems with much lower doses and dosages than the systemic route seems to be the most valuable option in fracture healing. However, systemic delivery of Simvastatin with much higher doses and dosages than the clinical ones seems to be effective in managing osteoporosis. Simvastatin, in a particular range of doses and dosages, may be beneficial in managing osteoporosis and fracture injuries. This review showed that Simvastatin is effective in the treatment of osteoporosis and fracture healing.
    Matched MeSH terms: Cell Differentiation/drug effects
  5. Dong J, Tao L, Abourehab MAS, Hussain Z
    Int J Biol Macromol, 2018 Sep;116:1268-1281.
    PMID: 29782984 DOI: 10.1016/j.ijbiomac.2018.05.116
    Osteoporosis is a medical condition of fragile bones with an increased susceptibility to fracture. Despite having availability of a wide range of pharmacological agents, prevalence of osteoporosis is continuously escalating. Owing to excellent biomedical achievements of nanomedicines in the last few decades, we aimed combo-delivery of bone anti-resorptive agent, alendronate (ALN), and bone density enhancing drug, curcumin (CUR) in the form of polymeric nanoparticles. To further optimize the therapeutic efficacy, the prepared ALN/CUR nanoparticles (NPs) were decorated with hyaluronic acid (HA) which is a well-documented biomacromolecule having exceptional bone regenerating potential. The optimized nanoformulation was then evaluated for bone regeneration efficacy by assessing time-mannered modulation in the proliferation, differentiation, and mineralization of MC3T3-E1 cells, a pre-osteoblastic model. Moreover, the time-mannered expression of various bone-forming protein biomarkers such as bone morphogenetic protein, runt related transcription factor 2, and osteocalcin were assessed in the cell lysates. Results revealed that HA-ALN/CUR NPs provoke remarkable increase in the proliferation, differentiation, and mineralization in the ECM of MC3T3-E1 cells which ultimately leads to enhanced bone formation. This new strategy of employing simultaneous delivery of anti-resorptive and bone forming agents would open new horizons for scientists as an efficient alternative pharmacotherapy for the management of osteoporosis.
    Matched MeSH terms: Cell Differentiation/drug effects
  6. Khalilpourfarshbafi M, Devi Murugan D, Abdul Sattar MZ, Sucedaram Y, Abdullah NA
    PLoS One, 2019;14(6):e0218792.
    PMID: 31226166 DOI: 10.1371/journal.pone.0218792
    The increased prevalence of obesity and associated insulin resistance calls for effective therapeutic treatment of metabolic diseases. The current PPARγ-targeting antidiabetic drugs have undesirable side effects. The present study investigated the anti-diabetic and anti-obesity effects of withaferin A (WFA) in diet-induced obese (DIO) C57BL/6J mice and also the anti-adipogenic effect of WFA in differentiating 3T3- F442A cells. DIO mice were treated with WFA (6 mg/kg) or rosiglitazone (10 mg/kg) for 8 weeks. At the end of the treatment period, metabolic profile, liver function and inflammatory parameters were obtained. Expression of selective genes controlling insulin signaling, inflammation, adipogenesis, energy expenditure and PPARγ phosphorylation-regulated genes in epididymal fats were analyzed. Furthermore, the anti-adipogenic effect of WFA was evaluated in 3T3- F442A cell line. WFA treatment prevented weight gain without affecting food or caloric intake in DIO mice. WFA-treated group also exhibited lower epididymal and mesenteric fat pad mass, an improvement in lipid profile and hepatic steatosis and a reduction in serum inflammatory cytokines. Insulin resistance was reduced as shown by an improvement in glucose and insulin tolerance and serum adiponectin. WFA treatment upregulated selective insulin signaling (insr, irs1, slc2a4 and pi3k) and PPARγ phosphorylation-regulated (car3, selenbp1, aplp2, txnip, and adipoq) genes, downregulated inflammatory (tnf-α and il-6) genes and altered energy expenditure controlling (tph2 and adrb3) genes. In 3T3- F442A cell line, withaferin A inhibited adipogenesis as indicated by a decrease in lipid accumulation in differentiating adipocytes and protein expression of PPARγ and C/EBPα. The effect of rosiglitazone on physiological and lipid profiles, insulin resistance, some genes expression and differentiating adipocytes were markedly different. Our data suggest that WFA is a promising therapeutic agent for both diabetes and obesity.
    Matched MeSH terms: Cell Differentiation/drug effects
  7. Yap WH, Cheah TY, Yong LC, Chowdhury SR, Ng MH, Kwan Z, et al.
    J Biosci, 2021;46.
    PMID: 34475316
    Psoriasis is a chronic skin disease characterized by thickening and disorganization of the skin's protective barrier. Although current models replicate some aspects of the disease, development of therapeutic strategies have been hindered by absence of more relevant models. This study aimed to develop and characterize an in vitro psoriatic human skin equivalent (HSE) using human keratinocytes HaCat cell line grown on fibroblasts-derived matrices (FDM). The constructed HSEs were treated with cytokines (IL-1α, TNF-α, IL-6, and IL22) to allow controlled induction of psoriasis-associated features. Histological stainings showed that FDMHSE composed of a fully differentiated epidermis and fibroblast-populated dermis comparable to native skin and rat tail collagen-HSE. Hyperproliferation (CK16 and Ki67) and inflammatory markers (TNF-α and IL-6) expression were significantly enhanced in the cytokine-induced FDM- and rat tail collagen HSEs compared to non-treated HSE counterparts. The characteristics were in line with those observed in psoriasis punch biopsies. Treatment with all-trans retinoic acid (ATRA) has shown to suppress these effects, where HSE models treated with both ATRA and cytokines exhibit histological characteristics, hyperproliferation and differentiation markers expression like non-treated control HSEs. Cytokine-induced FDM-HSE, constructed entirely from human cell lines, provides an excellent opportunity for psoriasis research and testing new therapeutics.
    Matched MeSH terms: Cell Differentiation/drug effects*
  8. Vimalraj S, Rajalakshmi S, Raj Preeth D, Vinoth Kumar S, Deepak T, Gopinath V, et al.
    Mater Sci Eng C Mater Biol Appl, 2018 Feb 01;83:187-194.
    PMID: 29208278 DOI: 10.1016/j.msec.2017.09.005
    Copper(II) complex of quercetin Cu+Q, mixed ligand complexes, quercetin-Cu(II)-phenanthroline [Cu+Q(PHt)] and quercetin-Cu(II)-neocuproine [Cu+Q(Neo)] have been synthesized and characterized. From the FT-IR spectroscopic studies, it was evident that C-ring of quercetin is involved in the metal chelation in all the three copper complexes. C-ring chelation was further proven by UV-Visible spectra and the presence of Cu(II) from EPR spectroscopic investigations. These complexes were found to have osteogenic and angiogenic properties, observed through in vitro osteoblast differentiation and chick embryo angiogenesis assay. In osteoblast differentiation, quercetin-Cu(II) complexes treatment increased calcium deposition and alkaline phosphatase activity (ALP) activity at the cellular level and stimulated Runx2 mRNA and protein, ALP mRNA and type 1 collagen mRNA expression at the molecular level. Among the complexes, Q+Cu(PHt) showed more effects on osteoblast differentiation when compared to that of other two copper complexes. Additionally, Q+Cu(Neo) showed more effect compared to Q+Cu. Furthermore, the effect of these complexes on osteoblast differentiation was confirmed by the expression of osteoblast specific microRNA, pre-mir-15b. The chick embryo angiogenesis assay showed that angiogenic parameters such as blood vessel length, size and junctions were stimulated by these complexes. Thus, the present study demonstrated that quercetin copper(II) complexes exhibit as a pharmacological agent for the orthopedic application.
    Matched MeSH terms: Cell Differentiation/drug effects
  9. Shi X, Xu L, Le TB, Zhou G, Zheng C, Tsuru K, et al.
    Mater Sci Eng C Mater Biol Appl, 2016 Feb;59:542-548.
    PMID: 26652406 DOI: 10.1016/j.msec.2015.10.024
    Dental implants made of pure titanium suffer from abrasion and scratch during routine oral hygiene procedures. This results in an irreversible surface damage, facilitates bacteria adhesion and increases risk of peri-implantitis. To overcome these problems, titanium nitride (TiN) coating was introduced to increase surface hardness of pure titanium. However, the osteoconductivity of TiN is considered to be similar or superior to that of titanium and its alloys and therefore surface modification is necessary. In this study, TiN coating prepared through gas nitriding was partially oxidized by hydrothermal (HT) treatment and ozone (O3) treatment in pure water to improve its osteoconductivity. The effects of HT treatment and O3 treatment on surface properties of TiN were investigated and the osteoconductivity after undergoing treatment was assessed in vitro using osteoblast evaluation. The results showed that the critical temperature for HT treatment was 100°C since higher temperatures would impair the hardness of TiN coating. By contrast, O3 treatment was more effective in oxidizing TiN surfaces, improving its wettability while preserving its morphology and hardness. Osteoblast attachment, proliferation, alkaline phosphatase (ALP) expression and mineralization were improved on oxidized specimens, especially on O3 treated specimens, compared with untreated ones. These effects seemed to be consequences of partial oxidation, as well as improved hydrophilicity and surface decontamination. Finally, it was concluded that, partially oxidized TiN is a promising coating to be used for dental implant.
    Matched MeSH terms: Cell Differentiation/drug effects
  10. Kumar SS, Alarfaj AA, Munusamy MA, Singh AJ, Peng IC, Priya SP, et al.
    Int J Mol Sci, 2014;15(12):23418-47.
    PMID: 25526563 DOI: 10.3390/ijms151223418
    Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold promise as novel therapeutic tools for diabetes treatment because of their self-renewal capacity and ability to differentiate into beta (β)-cells. Small and large molecules play important roles in each stage of β-cell differentiation from both hESCs and hiPSCs. The small and large molecules that are described in this review have significantly advanced efforts to cure diabetic disease. Lately, effective protocols have been implemented to induce hESCs and human mesenchymal stem cells (hMSCs) to differentiate into functional β-cells. Several small molecules, proteins, and growth factors promote pancreatic differentiation from hESCs and hMSCs. These small molecules (e.g., cyclopamine, wortmannin, retinoic acid, and sodium butyrate) and large molecules (e.g. activin A, betacellulin, bone morphogentic protein (BMP4), epidermal growth factor (EGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), noggin, transforming growth factor (TGF-α), and WNT3A) are thought to contribute from the initial stages of definitive endoderm formation to the final stages of maturation of functional endocrine cells. We discuss the importance of such small and large molecules in uniquely optimized protocols of β-cell differentiation from stem cells. A global understanding of various small and large molecules and their functions will help to establish an efficient protocol for β-cell differentiation.
    Matched MeSH terms: Cell Differentiation/drug effects*
  11. Abdullah M, Rahman FA, Gnanasegaran N, Govindasamy V, Abu Kasim NH, Musa S
    ScientificWorldJournal, 2014;2014:235941.
    PMID: 24616615 DOI: 10.1155/2014/235941
    Lead (Pb(2+)) exposure continues to be a significant public health problem. Therefore, it is vital to have a continuous epidemiological dataset for a better understanding of Pb(2+) toxicity. In the present study, we have exposed stem cells isolated from deciduous and permanent teeth, periodontal ligament, and bone marrow to five different types of Pb(2+) concentrations (160, 80, 40, 20, and 10 µM) for 24 hours to identify the adverse effects of Pb(2+) on the proliferation, differentiation, and gene expression on these cell lines. We found that Pb(2+) treatment altered the morphology and adhesion of the cells in a dose-dependent manner. There were no significant changes in terms of cell surface phenotypes. Cells exposed to Pb(2+) continued to differentiate into chondrogenesis and adipogenesis, and a severe downregulation was observed in osteogenesis. Gene expression studies revealed a constant expression of key markers associated with stemness (Oct 4, Rex 1) and DNA repair enzyme markers, but downregulation occurred with some ectoderm and endoderm markers, demonstrating an irregular and untimely differentiation trail. Our study revealed for the first time that Pb(2+) exposure not only affects the phenotypic characteristics but also induces significant alteration in the differentiation and gene expression in the cells.
    Matched MeSH terms: Cell Differentiation/drug effects*
  12. Hadzir SN, Ibrahim SN, Abdul Wahab RM, Zainol Abidin IZ, Senafi S, Ariffin ZZ, et al.
    Cytotherapy, 2014 May;16(5):674-82.
    PMID: 24176546 DOI: 10.1016/j.jcyt.2013.07.013
    Suspension mononuclear cells (MNCs) can be differentiated into osteoblasts with the induction of ascorbic acid and β-glycerophosphate. The aim of this study was to determine the ability of suspension MNCs to differentiate into osteoblasts using ascorbic acid only.
    Matched MeSH terms: Cell Differentiation/drug effects*
  13. Mat MC, Mohamed AS, Hamid SS
    Lipids Health Dis, 2011;10:216.
    PMID: 22104447 DOI: 10.1186/1476-511X-10-216
    Oxidized low density lipoprotein plays an important role in development of foam cells in atherosclerosis. The study was focused on regulation of primary human monocyte growth and CD11b expression in presence of Nigella sativa oil.
    Matched MeSH terms: Cell Differentiation/drug effects*
  14. Fatimah SS, Tan GC, Chua K, Tan AE, Nur Azurah AG, Hayati AR
    Burns, 2013 Aug;39(5):905-15.
    PMID: 23273814 DOI: 10.1016/j.burns.2012.10.019
    The aim of the present study was to determine the effects of KGF on the differentiation of cultured human amnion epithelial cells (HAECs) towards skin keratinocyte. HAECs at passage 1 were cultured in medium HAM's F12: Dulbecco's Modified Eagles Medium (1:1) supplemented with different concentrations of KGF (0, 5, 10, 20, 30 and 50 ng/ml KGF). Dose-response of KGF on HAECs was determined by morphological assessment; growth kinetic evaluation; immunocytochemical analysis; stemness and epithelial gene expression quantification with two step real time RT-PCR. KGF promotes the proliferation of HAECs with maximal effect observed at 10 ng/ml KGF. However, KGF decreased the stemness genes expression: Oct-3/4, Sox-2, Nanog3, Rex-1, FGF-4, FZD-9 and BST-1. KGF also down-regulates epithelial genes expression: CK3, CK18, CK19, Integrin-β1, p63 and involucrin in cultured HAECs. No significant difference on the gene expression was detected for each Nestin, ABCG-2, CK1 and CK14 in KGF-treated HAECs. Immunocytochemical analysis for both control and KGF-treated HAECs demonstrated positive staining against CK14 and CK18 but negative staining against involucrin. The results suggested that KGF stimulates an early differentiation of HAECs towards epidermal cells. Differentiation of KGF-treated HAECs to corneal lineage is unfavourable. Therefore, further studies are needed to elucidate the roles of KGF in the differentiation of HAECs towards skin keratinocytes.
    Matched MeSH terms: Cell Differentiation/drug effects*
  15. Nouri F, Salehinejad P, Nematollahi-Mahani SN, Kamarul T, Zarrindast MR, Sharifi AM
    Cell Mol Neurobiol, 2016 Jul;36(5):689-700.
    PMID: 26242172 DOI: 10.1007/s10571-015-0249-8
    Transplantation of neural-like cells is considered as a promising therapeutic strategy developed for neurodegenerative disease in particular for ischemic stroke. Since cell survival is a major concern following cell implantation, a number of studies have underlined the protective effects of preconditioning with hypoxia or hypoxia mimetic pharmacological agents such as deferoxamine (DFO), induced by activation of hypoxia inducible factor-1 (HIF-1) and its target genes. The present study has investigated the effects of DFO preconditioning on some factors involved in cell survival, angiogenesis, and neurogenesis of neural-like cells derived from human Wharton's jelly mesenchymal stem cells (HWJ-MSCs) in presence of hydrogen peroxide (H2O2). HWJ-MSCs were differentiated toward neural-like cells for 14 days and neural cell markers were identified using immunocytochemistry. HWJ-MSC-derived neural-like cells were then treated with 100 µM DFO, as a known hypoxia mimetic agent for 48 h. mRNA and protein expression of HIF-1 target genes including brain-derived neurotrophic factors (BDNF) and vascular endothelial growth factor (VEGF) significantly increased using RT-PCR and Western blotting which were reversed by HIF-1α inhibitor, while, gene expression of Akt-1, Bcl-2, and Bax did not change significantly but pAkt-1 was up-regulated as compared to poor DFO group. However, addition of H2O2 to DFO-treated cells resulted in higher resistance to H2O2-induced cell death. Western blotting analysis also showed significant up-regulation of HIF-1α, BDNF, VEGF, and pAkt-1, and decrease of Bax/Bcl-2 ratio as compared to poor DFO. These results may suggest that DFO preconditioning of HWJ-MSC-derived neural-like cells improves their tolerance and therapeutic potential and might be considered as a valuable strategy to improve cell therapy.
    Matched MeSH terms: Cell Differentiation/drug effects*
  16. Hapidin H, Romli NAA, Abdullah H
    Microsc Res Tech, 2019 Nov;82(11):1928-1940.
    PMID: 31423711 DOI: 10.1002/jemt.23361
    Tannic acid (TA) is a phenolic compound that might act directly on osteoblast metabolism. The study was performed to investigate the effects of TA on the proliferation, mineralization, and morphology of human fetal osteoblast cells (hFOB 1.19). The cells were divided into TA-treated, untreated, and pamidronate-treated (control drug) groups. Half maximal effective concentration (EC50 ) values for TA and pamidronate were measured using MTT assay. The EC50 of hFOB 1.19 cells treated with TA was 2.94 M. This concentration was more effective compared to the pamidronate (15.27 M). Cell proliferation assay was performed to compare cell viability from Day 1 until Day 14. The morphology of hFOB 1.19 was observed via inverted microscope and scanning electron microscope. Calcium (Ca) and phosphate (P) were assessed using energy-dispersive X-ray (EDX) analysis. Furthermore, the mineralization of hFOB 1.19 was determined by von Kossa staining (P depositions) and Alizarin Red S staining (Ca depositions). The number of cells treated with TA was significantly higher than the two control groups at Day 10 and Day 14. The morphology of cells treated with TA was uniformly fusiform-shaped with filopodia extensions. Besides, globular-like structures of deposited minerals were observed in the TA-treated group. In line with other findings, EDX spectrum analysis confirmed the presence of Ca and P. The cells treated with TA had significantly higher percentage of both minerals at Day 3 and Day 10 compared to the two control groups. In conclusion, TA enhances cell proliferation and causes cell morphology changes, as well as improved mineralization.
    Matched MeSH terms: Cell Differentiation/drug effects
  17. Musa M, Ouaret D, Bodmer WF
    Anticancer Res, 2020 Nov;40(11):6063-6073.
    PMID: 33109544 DOI: 10.21873/anticanres.14627
    BACKGROUND/AIM: Interactions between colorectal cancer (CRC) cells and myofibroblasts govern many processes such as cell growth, migration, invasion and differentiation, and contribute to CRC progression. Robust experimental tests are needed to investigate the nature of these interactions for future anticancer studies. The purpose of the study was to design and validate in vitro assays for studying the communication between myofibroblasts and CRC epithelial cell lines.

    MATERIALS AND METHODS: The influence of co-culture of myofibroblasts and CRC cell lines is discussed using various in vitro assays including direct co-culture, transwell assays, Matrigel-based differentiation and cell invasion experiments.

    RESULTS: The results from these in vitro assays clearly demonstrated various aspects of the crosstalk between myofibroblasts and CRC cell lines, which include cell growth, differentiation, migration and invasion.

    CONCLUSION: The reported in vitro assays provide a basis for investigating the factors that control the myofibroblast-epithelial cell interactions in CRC in vivo.

    Matched MeSH terms: Cell Differentiation/drug effects
  18. Morita H, Nugroho AE, Nagakura Y, Hirasawa Y, Yoshida H, Kaneda T, et al.
    Bioorg Med Chem Lett, 2014 Jun 1;24(11):2437-9.
    PMID: 24767841 DOI: 10.1016/j.bmcl.2014.04.020
    Four new chromone alkaloids, chrotacumines G-J (1-4), have been isolated from the barks of Dysoxylum acutangulum. Their structures and absolute configurations were elucidated on the basis of NMR and CD data. Chrotacumines G and J (1 and 4) showed osteoclast differentiation inhibitory activity in a dose dependent manner.
    Matched MeSH terms: Cell Differentiation/drug effects
  19. Vinoth KJ, Manikandan J, Sethu S, Balakrishnan L, Heng A, Lu K, et al.
    J Biotechnol, 2014 Aug 20;184:154-68.
    PMID: 24862194 DOI: 10.1016/j.jbiotec.2014.05.009
    This study evaluated human embryonic stem cells (hESC) and their differentiated fibroblastic progenies as cellular models for genotoxicity screening. The DNA damage response of hESCs and their differentiated fibroblastic progenies were compared to a fibroblastic cell line (HEPM, CRL1486) and primary cultures of peripheral blood lymphocytes (PBL), upon exposure to Mitomycin C, gamma irradiation and H2O2. It was demonstrated that hESC-derived fibroblastic progenies (H1F) displayed significantly higher chromosomal aberrations, micronuclei formation and double strand break (DSB) formation, as compared to undifferentiated hESC upon exposure to genotoxic stress. Nevertheless, H1F cell types displayed comparable sensitivities to genotoxic challenge as HEPM and PBL, both of which are representative of somatic cell types commonly used for genotoxicity screening. Subsequently, transcriptomic and pathways analysis identified differential expression of critical genes involved in cell death and DNA damage response upon exposure to gamma irradiation. The results thus demonstrate that hESC-derived fibroblastic progenies are as sensitive as commonly-used somatic cell types for genotoxicity screening. Moreover, hESCs have additional advantages, such as their genetic normality compared to immortalized cell lines, as well as their amenability to scale-up for producing large, standardized quantities of cells for genotoxicity screening on an industrial scale, something which can never be achieved with primary cell cultures.
    Matched MeSH terms: Cell Differentiation/drug effects*
  20. Magalingam KB, Radhakrishnan AK, Somanath SD, Md S, Haleagrahara N
    Mol Biol Rep, 2020 Nov;47(11):8775-8788.
    PMID: 33098048 DOI: 10.1007/s11033-020-05925-2
    Numerous protocols to establish dopaminergic phenotype in SH-SY5Y cells have been reported. In most of these protocols there are variations in concentration of serum used. In this paper, we compared the effects of high (10%), low (3%) and descending (2.5%/1%) serum concentration in differentiation medium containing different proportion of retinoic acid (RA) and 12-O-Tetradecanoylphorbol-13-acetate (TPA) or RA-only on the undifferentiated SH-SY5Y cells with regards to cell morphology, biochemical and gene expression alterations. Cells differentiated in culture medium containing low and descending serum concentrations showed increased number of neurite projections and reduced proliferation rates when compared to undifferentiated cells. The SH-SY5Y cells differentiated in culture medium containing 3% RA and low serum or descending (2.5%/1% RA/TPA) were found to be more susceptible to 6-hydroxydopamine (6-OHDA) induced cytotoxicity. Cells differentiated with RA/TPA or RA differentiated showed increased production of the α-synuclein (SNCA) neuroprotein and dopamine neurotransmitter compared to undifferentiated cells, regardless serum concentrations used. There was no significant difference in the expression of tyrosine hydroxylase (TH) gene between undifferentiated and differentiated SH-SY5Y cells. However, the expression of dopamine receptor D2 (DRD2) gene was markedly increased (p<0.05) in differentiated cells with 3% serum and RA only when compared to undifferentiated cells. In conclusion, to terminally differentiate SH-SY5Y cells to be used as a cell-based model to study Parkinson's disease (PD) to investigate molecular mechanisms and drug discovery, the optimal differentiation medium should contain 3% serum in RA-only.
    Matched MeSH terms: Cell Differentiation/drug effects*
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