Displaying publications 1 - 20 of 105 in total

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  1. Fulltext Cockle Shell-Derived Aragonite CaCO3 Nanoparticles for Co-Delivery of Doxorubicin and Thymoquinone Eliminates Cancer Stem Cells
    Ibiyeye KM, Zuki ABZ
    Int J Mol Sci, 2020 Mar 10;21(5).
    PMID: 32164352 DOI: 10.3390/ijms21051900
    Cancer stem cells CSCs (tumour-initiating cells) are responsible for cancer metastasis and recurrence associated with resistance to conventional chemotherapy. This study generated MBA MD231 3D cancer stem cells enriched spheroids in serum-free conditions and evaluated the influence of combined doxorubicin/thymoquinone-loaded cockle-shell-derived aragonite calcium carbonate nanoparticles. Single loaded drugs and free drugs were also evaluated. WST assay, sphere forming assay, ALDH activity analysis, Surface marker of CD44 and CD24 expression, apoptosis with Annexin V-PI kit, cell cycle analysis, morphological changes using a phase contrast light microscope, scanning electron microscopy, invasion assay and migration assay were carried out; The combination therapy showed enhanced apoptosis, reduction in ALDH activity and expression of CD44 and CD24 surface maker, reduction in cellular migration and invasion, inhibition of 3D sphere formation when compared to the free drugs and the single drug-loaded nanoparticle. Scanning electron microscopy showed poor spheroid formation, cell membrane blebbing, presence of cell shrinkage, distortion in the spheroid architecture; and the results from this study showed that combined drug-loaded cockle-shell-derived aragonite calcium carbonate nanoparticles can efficiently destroy the breast CSCs compared to single drug-loaded nanoparticle and a simple mixture of doxorubicin and thymoquinone.
    Matched MeSH terms: Neoplastic Stem Cells/metabolism
  2. CRISPR/Cas9 in Stem Cell Research: Current Application and Future Perspective
    Patmanathan SN, Gnanasegaran N, Lim MN, Husaini R, Fakiruddin KS, Zakaria Z
    Curr Stem Cell Res Ther, 2018;13(8):632-644.
    PMID: 29895256 DOI: 10.2174/1574888X13666180613081443
    The clustered regularly interspaced short palindromic repeats-associated protein 9 or CRISPR/Cas9 system is one of the hottest topics discussed lately due to its robustness and effectiveness in genome editing. The technology has been widely used in life science research including microbial, plant, animal, and human cell studies. Combined with the pluripotency of stem cells, the technology represents a powerful tool to generate various cell types for disease modeling, drug screening, toxicology, and targeted therapies. Generally, the CRISPR/Cas9 system has been applied in genetic modification of pluripotent or multipotent stem cells, after which the cells are differentiated into specific cell types and used for functional analysis or even clinical transplantation. Recent advancement in CRISPR/Cas9 technology has widened the scope of stem cell research and its therapeutic application. This review provides an overview of the current application and the prospect of CRISPR/Cas9 technology, particularly in stem cell research and therapy.
    Matched MeSH terms: Stem Cells/metabolism
  3. Ex vivo expanded SSEA-4+ human limbal stromal cells are multipotent and do not express other embryonic stem cell markers
    Lim MN, Hussin NH, Othman A, Umapathy T, Baharuddin P, Jamal R, et al.
    Mol Vis, 2012;18:1289-300.
    PMID: 22665977
    The presence of multipotent human limbal stromal cells resembling mesenchymal stromal cells (MSC) provides new insights to the characteristic of these cells and its therapeutic potential. However, little is known about the expression of stage-specific embryonic antigen 4 (SSEA-4) and the embryonic stem cell (ESC)-like properties of these cells. We studied the expression of SSEA-4 surface protein and the various ESC and MSC markers in the ex vivo cultured limbal stromal cells. The phenotypes and multipotent differentiation potential of these cells were also evaluated.
    Matched MeSH terms: Multipotent Stem Cells/metabolism
  4. Fulltext REST and Neural Gene Network Dysregulation in iPSC Models of Alzheimer's Disease
    Meyer K, Feldman HM, Lu T, Drake D, Lim ET, Ling KH, et al.
    Cell Rep, 2019 01 29;26(5):1112-1127.e9.
    PMID: 30699343 DOI: 10.1016/j.celrep.2019.01.023
    The molecular basis of the earliest neuronal changes that lead to Alzheimer's disease (AD) is unclear. Here, we analyze neural cells derived from sporadic AD (SAD), APOE4 gene-edited and control induced pluripotent stem cells (iPSCs). We observe major differences in iPSC-derived neural progenitor (NP) cells and neurons in gene networks related to neuronal differentiation, neurogenesis, and synaptic transmission. The iPSC-derived neural cells from SAD patients exhibit accelerated neural differentiation and reduced progenitor cell renewal. Moreover, a similar phenotype appears in NP cells and cerebral organoids derived from APOE4 iPSCs. Impaired function of the transcriptional repressor REST is strongly implicated in the altered transcriptome and differentiation state. SAD and APOE4 expression result in reduced REST nuclear translocation and chromatin binding, and disruption of the nuclear lamina. Thus, dysregulation of neural gene networks may set in motion the pathologic cascade that leads to AD.
    Matched MeSH terms: Induced Pluripotent Stem Cells/metabolism*; Neural Stem Cells/metabolism
  5. Fulltext Expression of Endogenous Angiotensin-Converting Enzyme 2 in Human Induced Pluripotent Stem Cell-Derived Retinal Organoids
    Ahmad Mulyadi Lai HI, Chou SJ, Chien Y, Tsai PH, Chien CS, Hsu CC, et al.
    Int J Mol Sci, 2021 Jan 28;22(3).
    PMID: 33525682 DOI: 10.3390/ijms22031320
    Angiotensin-converting enzyme 2 (ACE2) was identified as the main host cell receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent infection. In some coronavirus disease 2019 (COVID-19) patients, it has been reported that the nervous tissues and the eyes were also affected. However, evidence supporting that the retina is a target tissue for SARS-CoV-2 infection is still lacking. This present study aimed to investigate whether ACE2 expression plays a role in human retinal neurons during SARS-CoV-2 infection. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids and monolayer cultures derived from dissociated retinal organoids were generated. To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal organoids and monolayer cultures. Furthermore, using the SARS-CoV-2 pseudovirus spike protein with GFP expression system, we found that retinal organoids and monolayer cultures can potentially be infected by the SARS-CoV-2 pseudovirus. Collectively, our findings highlighted the potential of iPSC-derived retinal organoids as the models for ACE2 receptor-based SARS-CoV-2 infection.
    Matched MeSH terms: Induced Pluripotent Stem Cells/metabolism
  6. Fulltext Synergistic Roles of Curcumin in Sensitising the Cisplatin Effect on a Cancer Stem Cell-Like Population Derived from Non-Small Cell Lung Cancer Cell Lines
    Abdul Satar N, Ismail MN, Yahaya BH
    Molecules, 2021 Feb 18;26(4).
    PMID: 33670440 DOI: 10.3390/molecules26041056
    Cancer stem cells (CSCs) represent a small subpopulation within a tumour. These cells possess stem cell-like properties but also initiate resistance to cytotoxic agents, which contributes to cancer relapse. Natural compounds such as curcumin that contain high amounts of polyphenols can have a chemosensitivity effect that sensitises CSCs to cytotoxic agents such as cisplatin. This study was designed to investigate the efficacy of curcumin as a chemo-sensitiser in CSCs subpopulation of non-small cell lung cancer (NSCLC) using the lung cancer adenocarcinoma human alveolar basal epithelial cells A549 and H2170. The ability of curcumin to sensitise lung CSCs to cisplatin was determined by evaluating stemness characteristics, including proliferation activity, colony formation, and spheroid formation of cells treated with curcumin alone, cisplatin alone, or the combination of both at 24, 48, and 72 h. The mRNA level of genes involved in stemness was analysed using quantitative real-time polymerase chain reaction. Liquid chromatography-mass spectrometry was used to evaluate the effect of curcumin on the CSC niche. A combined treatment of A549 subpopulations with curcumin reduced cellular proliferation activity at all time points. Curcumin significantly (p < 0.001) suppressed colonies formation by 50% and shrank the spheroids in CSC subpopulations, indicating inhibition of their self-renewal capability. This effect also was manifested by the down-regulation of SOX2, NANOG, and KLF4. Curcumin also regulated the niche of CSCs by inhibiting chemoresistance proteins, aldehyde dehydrogenase, metastasis, angiogenesis, and proliferation of cancer-related proteins. These results show the potential of using curcumin as a therapeutic approach for targeting CSC subpopulations in non-small cell lung cancer.
    Matched MeSH terms: Neoplastic Stem Cells/metabolism
  7. Fulltext Stimulatory Secretions of Airway Epithelial Cells Accelerate Early Repair of Tracheal Epithelium
    Kardia E, Mohamed R, Yahaya BH
    Sci Rep, 2017 09 15;7(1):11732.
    PMID: 28916766 DOI: 10.1038/s41598-017-11992-6
    Airway stem/progenitor epithelial cells (AECs) are notable for their differentiation capacities in response to lung injury. Our previous finding highlighted the regenerative capacity of AECs following transplantation in repairing tracheal injury and reducing the severity of alveolar damage associated acute lung injury in a rabbit model. The goal of this study is to further investigate the potential of AECs to re-populate the tracheal epithelium and to study their stimulatory effect on inhibiting pro-inflammatory cytokines, epithelial cell migration and proliferation, and epithelial-to-mesenchymal transition (EMT) process following tracheal injury. Two in vitro culture assays were applied in this study; the direct co-culture assay that involved a culture of decellularised tracheal epithelium explants and AECs in a rotating tube, and indirect co-culture assay that utilized microporous membrane-well chamber system to separate the partially decellularised tracheal epithelium explants and AEC culture. The co-culture assays provided evidence of the stimulatory behaviour of AECs to enhance tracheal epithelial cell proliferation and migration during early wound repair. Factors that were secreted by AECs also markedly suppressed the production of IL-1β and IL-6 and initiated the EMT process during tracheal remodelling.
    Matched MeSH terms: Stem Cells/metabolism
  8. Fulltext Curcumin improves the efficacy of cisplatin by targeting cancer stem-like cells through p21 and cyclin D1-mediated tumour cell inhibition in non-small cell lung cancer cell lines
    Baharuddin P, Satar N, Fakiruddin KS, Zakaria N, Lim MN, Yusoff NM, et al.
    Oncol Rep, 2016 Jan;35(1):13-25.
    PMID: 26531053 DOI: 10.3892/or.2015.4371
    Natural compounds such as curcumin have the ability to enhance the therapeutic effectiveness of common chemotherapy agents through cancer stem-like cell (CSC) sensitisation. In the present study, we showed that curcumin enhanced the sensitivity of the double-positive (CD166+/EpCAM+) CSC subpopulation in non-small cell lung cancer (NSCLC) cell lines (A549 and H2170) to cisplatin-induced apoptosis and inhibition of metastasis. Our results revealed that initial exposure of NSCLC cell lines to curcumin (10-40 µM) markedly reduced the percentage of viability to an average of ~51 and ~54% compared to treatment with low dose cisplatin (3 µM) with only 94 and 86% in both the A549 and H2170 cells. Moreover, sensitisation of NSCLC cell lines to curcumin through combined treatment enhanced the single effect induced by low dose cisplatin on the apoptosis of the double-positive CSC subpopulation by 18 and 20% in the A549 and H2170 cells, respectively. Furthermore, we found that curcumin enhanced the inhibitory effects of cisplatin on the highly migratory CD166+/EpCAM+ subpopulation, marked by a reduction in cell migration to 9 and 21% in the A549 and H2170 cells, respectively, indicating that curcumin may increase the sensitivity of CSCs to cisplatin-induced migratory inhibition. We also observed that the mRNA expression of cyclin D1 was downregulated, while a substantial increased in p21 expression was noted, followed by Apaf1 and caspase-9 activation in the double-positive (CD166+/EpCAM+) CSC subpopulation of A549 cells, suggested that the combined treatments induced cell cycle arrest, therefore triggering CSC growth inhibition via the intrinsic apoptotic pathway. In conclusion, we provided novel evidence of the previously unknown therapeutic effects of curcumin, either alone or in combination with cisplatin on the inhibition of the CD166+/EpCAM+ subpopulation of NSCLC cell lines. This finding demonstrated the potential therapeutic approach of using curcumin that may enhance the effects of cisplatin by targeting the CSC subpopulation in NSCLC.
    Matched MeSH terms: Neoplastic Stem Cells/metabolism
  9. Fulltext Human non-small cell lung cancer expresses putative cancer stem cell markers and exhibits the transcriptomic profile of multipotent cells
    Zakaria N, Yusoff NM, Zakaria Z, Lim MN, Baharuddin PJ, Fakiruddin KS, et al.
    BMC Cancer, 2015;15:84.
    PMID: 25881239 DOI: 10.1186/s12885-015-1086-3
    Despite significant advances in staging and therapies, lung cancer remains a major cause of cancer-related lethality due to its high incidence and recurrence. Clearly, a novel approach is required to develop new therapies to treat this devastating disease. Recent evidence indicates that tumours contain a small population of cells known as cancer stem cells (CSCs) that are responsible for tumour maintenance, spreading and resistant to chemotherapy. The genetic composition of CSCs so far is not fully understood, but manipulation of the specific genes that maintain their integrity would be beneficial for developing strategies to combat cancer. Therefore, the goal of this study isto identify the transcriptomic composition and biological functions of CSCs from non-small cell lung cancer (NSCLC).
    Matched MeSH terms: Neoplastic Stem Cells/metabolism*
  10. Fulltext Extrinsic factors involved in the differentiation of stem cells into insulin-producing cells: an overview
    Wong RS
    Exp Diabetes Res, 2011;2011:406182.
    PMID: 21747828 DOI: 10.1155/2011/406182
    Diabetes mellitus is a chronic disease with many debilitating complications. Treatment of diabetes mellitus mainly revolves around conventional oral hypoglycaemic agents and insulin replacement therapy. Recently, scientists have turned their attention to the generation of insulin-producing cells (IPCs) from stem cells of various sources. To date, many types of stem cells of human and animal origins have been successfully turned into IPCs in vitro and have been shown to exert glucose-lowering effect in vivo. However, scientists are still faced with the challenge of producing a sufficient number of IPCs that can in turn produce sufficient insulin for clinical use. A careful choice of stem cells, methods, and extrinsic factors for induction may all be contributing factors to successful production of functional beta-islet like IPCs. It is also important that the mechanism of differentiation and mechanism by which IPCs correct hyperglycaemia are carefully studied before they are used in human subjects.
    Matched MeSH terms: Stem Cells/metabolism
  11. Fulltext Maintenance of active chromatin states by HMGN2 is required for stem cell identity in a pluripotent stem cell model
    Garza-Manero S, Sindi AAA, Mohan G, Rehbini O, Jeantet VHM, Bailo M, et al.
    Epigenetics Chromatin, 2019 12 12;12(1):73.
    PMID: 31831052 DOI: 10.1186/s13072-019-0320-7
    BACKGROUND: Members of the HMGN protein family modulate chromatin structure and influence epigenetic modifications. HMGN1 and HMGN2 are highly expressed during early development and in the neural stem/progenitor cells of the developing and adult brain. Here, we investigate whether HMGN proteins contribute to the chromatin plasticity and epigenetic regulation that is essential for maintaining pluripotency in stem cells.

    RESULTS: We show that loss of Hmgn1 or Hmgn2 in pluripotent embryonal carcinoma cells leads to increased levels of spontaneous neuronal differentiation. This is accompanied by the loss of pluripotency markers Nanog and Ssea1, and increased expression of the pro-neural transcription factors Neurog1 and Ascl1. Neural stem cells derived from these Hmgn-knockout lines also show increased spontaneous neuronal differentiation and Neurog1 expression. The loss of HMGN2 leads to a global reduction in H3K9 acetylation, and disrupts the profile of H3K4me3, H3K9ac, H3K27ac and H3K122ac at the Nanog and Oct4 loci. At endodermal/mesodermal genes, Hmgn2-knockout cells show a switch from a bivalent to a repressive chromatin configuration. However, at neuronal lineage genes whose expression is increased, no epigenetic changes are observed and their bivalent states are retained following the loss of HMGN2.

    CONCLUSIONS: We conclude that HMGN1 and HMGN2 maintain the identity of pluripotent embryonal carcinoma cells by optimising the pluripotency transcription factor network and protecting the cells from precocious differentiation. Our evidence suggests that HMGN2 regulates active and bivalent genes by promoting an epigenetic landscape of active histone modifications at promoters and enhancers.

    Matched MeSH terms: Pluripotent Stem Cells/metabolism; Neural Stem Cells/metabolism
  12. Impact of low oxygen tension on stemness, proliferation and differentiation potential of human adipose-derived stem cells
    Choi JR, Pingguan-Murphy B, Wan Abas WA, Noor Azmi MA, Omar SZ, Chua KH, et al.
    Biochem Biophys Res Commun, 2014 May 30;448(2):218-24.
    PMID: 24785372 DOI: 10.1016/j.bbrc.2014.04.096
    Adipose-derived stem cells (ASCs) have been found adapted to a specific niche with low oxygen tension (hypoxia) in the body. As an important component of this niche, oxygen tension has been known to play a critical role in the maintenance of stem cell characteristics. However, the effect of O2 tension on their functional properties has not been well determined. In this study, we investigated the effects of O2 tension on ASCs stemness, differentiation and proliferation ability. Human ASCs were cultured under normoxia (21% O2) and hypoxia (2% O2). We found that hypoxia increased ASC stemness marker expression and proliferation rate without altering their morphology and surface markers. Low oxygen tension further enhances the chondrogenic differentiation ability, but reduces both adipogenic and osteogenic differentiation potential. These results might be correlated with the increased expression of HIF-1α under hypoxia. Taken together, we suggest that growing ASCs under 2% O2 tension may be important in expanding ASCs effectively while maintaining their functional properties for clinical therapy, particularly for the treatment of cartilage defects.
    Matched MeSH terms: Stem Cells/metabolism*
  13. Fulltext Phenotypic and functional characterization of long-term cryopreserved human adipose-derived stem cells
    Yong KW, Pingguan-Murphy B, Xu F, Abas WA, Choi JR, Omar SZ, et al.
    Sci Rep, 2015;5:9596.
    PMID: 25872464 DOI: 10.1038/srep09596
    Cryopreservation represents an effective technique to maintain the functional properties of human adipose-derived stem cells (ASCs) and allows pooling of cells via long-term storage for clinical applications, e.g., cell-based therapies. It is crucial to reduce freezing injury during the cryopreservation process by loading the ASCs with the optimum concentration of suitable cryoprotective agents (CPAs). In this study, human ASCs were preserved for 3 months in different combinations of CPAs, including 1) 0.25 M trehalose; 2) 5% dimethylsulfoxide (DMSO); 3) 10% DMSO; 4) 5% DMSO + 20% fetal bovine serum (FBS); 5) 10% DMSO + 20% FBS; 6) 10% DMSO + 90% FBS. Interestingly, even with a reduction of DMSO to 5% and without FBS, cryopreserved ASCs maintained high cell viability comparable with standard cryomedium (10% DMSO + 90% FBS), with normal cell phenotype and proliferation rate. Cryopreserved ASCs also maintained their differentiation capability (e.g., to adipocytes, osteocytes and chondrocytes) and showed an enhanced expression level of stemness markers (e.g., NANOG, OCT-4, SOX-2 and REX-1). Our findings suggest that 5% DMSO without FBS may be an ideal CPA for an efficient long-term cryopreservation of human ASCs. These results aid in establishing standardized xeno-free long-term cryopreservation of human ASCs for clinical applications.
    Matched MeSH terms: Adult Stem Cells/metabolism*
  14. Fulltext Long-term xeno-free culture of human pluripotent stem cells on hydrogels with optimal elasticity
    Higuchi A, Kao SH, Ling QD, Chen YM, Li HF, Alarfaj AA, et al.
    Sci Rep, 2015 Dec 14;5:18136.
    PMID: 26656754 DOI: 10.1038/srep18136
    The tentative clinical application of human pluripotent stem cells (hPSCs), such as human embryonic stem cells and human induced pluripotent stem cells, is restricted by the possibility of xenogenic contamination resulting from the use of mouse embryonic fibroblasts (MEFs) as a feeder layer. Therefore, we investigated hPSC cultures on biomaterials with different elasticities that were grafted with different nanosegments. We prepared dishes coated with polyvinylalcohol-co-itaconic acid hydrogels grafted with an oligopeptide derived from vitronectin (KGGPQVTRGDVFTMP) with elasticities ranging from 10.3 to 30.4 kPa storage moduli by controlling the crosslinking time. The hPSCs cultured on the stiffest substrates (30.4 kPa) tended to differentiate after five days of culture, whereas the hPSCs cultured on the optimal elastic substrates (25 kPa) maintained their pluripotency for over 20 passages under xeno-free conditions. These results indicate that cell culture matrices with optimal elasticity can maintain the pluripotency of hPSCs in culture.
    Matched MeSH terms: Pluripotent Stem Cells/metabolism
  15. Fulltext A hybrid-membrane migration method to isolate high-purity adipose-derived stem cells from fat tissues
    Higuchi A, Wang CT, Ling QD, Lee HH, Kumar SS, Chang Y, et al.
    Sci Rep, 2015;5:10217.
    PMID: 25970301 DOI: 10.1038/srep10217
    Human adipose-derived stem cells (hADSCs) exhibit heterogeneous characteristics, indicating various genotypes and differentiation abilities. The isolated hADSCs can possess different purity levels and divergent properties depending on the purification methods used. We developed a hybrid-membrane migration method that purifies hADSCs from a fat tissue solution with extremely high purity and pluripotency. A primary fat-tissue solution was permeated through the porous membranes with a pore size from 8 to 25 μm, and the membranes were incubated in cell culture medium for 15-18 days. The hADSCs that migrated from the membranes contained an extremely high percentage (e.g., >98%) of cells positive for mesenchymal stem cell markers and showed almost one order of magnitude higher expression of some pluripotency genes (Oct4, Sox2, Klf4 and Nanog) compared with cells isolated using the conventional culture method.
    Matched MeSH terms: Adult Stem Cells/metabolism
  16. Fulltext Xeno-free culture of human pluripotent stem cells on oligopeptide-grafted hydrogels with various molecular designs
    Chen YM, Chen LH, Li MP, Li HF, Higuchi A, Kumar SS, et al.
    Sci Rep, 2017 03 23;7:45146.
    PMID: 28332572 DOI: 10.1038/srep45146
    Establishing cultures of human embryonic (ES) and induced pluripotent (iPS) stem cells in xeno-free conditions is essential for producing clinical-grade cells. Development of cell culture biomaterials for human ES and iPS cells is critical for this purpose. We designed several structures of oligopeptide-grafted poly (vinyl alcohol-co-itaconic acid) hydrogels with optimal elasticity, and prepared them in formations of single chain, single chain with joint segment, dual chain with joint segment, and branched-type chain. Oligopeptide sequences were selected from integrin- and glycosaminoglycan-binding domains of the extracellular matrix. The hydrogels grafted with vitronectin-derived oligopeptides having a joint segment or a dual chain, which has a storage modulus of 25 kPa, supported the long-term culture of human ES and iPS cells for over 10 passages. The dual chain and/or joint segment with cell adhesion molecules on the hydrogels facilitated the proliferation and pluripotency of human ES and iPS cells.
    Matched MeSH terms: Pluripotent Stem Cells/metabolism*; Embryonic Stem Cells/metabolism
  17. Application of multiplex PCR for characterization of human embryonic stem cells (hESCs) and its differentiated progenies
    Mamidi MK, Pal R, Bhonde R, Zakaria Z, Totey S
    J Biomol Screen, 2010 Jul;15(6):630-43.
    PMID: 20530724 DOI: 10.1177/1087057110370211
    Techniques to evaluate gene expression profiling, including real-time quantitative PCR, TaqMan low-density arrays, and sufficiently sensitive cDNA microarrays, are efficient methods for monitoring human embryonic stem cell (hESC) cultures. However, most of these high-throughput tests have a limited use due to high cost, extended turnaround time, and the involvement of highly specialized technical expertise. Hence, there is a paucity of rapid, cost-effective, robust, yet sensitive methods for routine screening of hESCs. A critical requirement in hESC cultures is to maintain a uniform undifferentiated state and to determine their differentiation capacity by showing the expression of gene markers representing all germ layers, including ecto-, meso-, and endoderm. To quantify the modulation of gene expression in hESCs during their propagation, expansion, and differentiation via embryoid body (EB) formation, the authors developed a simple, rapid, inexpensive, and definitive multimarker, semiquantitative multiplex RT-PCR (mxPCR) platform technology. Among the 15 gene primers tested, 4 were pluripotent markers comprising set 1, and 3 lineage-specific markers from each ecto-, meso-, and endoderm layers were combined as sets 2 to 4, respectively. The authors found that these 4 sets were not only effective in determining the relative differentiation in hESCs, but were easily reproducible. In this study, they used the HUES-7 cell line to standardize the technique, which was subsequently validated with HUES-9, NTERA-2, and mouse embryonic fibroblast cells. This single-reaction mxPCR assay was flexible and, by selecting appropriate reporter genes, can be designed for characterization of different hESC lines during routine maintenance and directed differentiation.
    Matched MeSH terms: Embryonic Stem Cells/metabolism*
  18. Interplay of autophagy and cancer stem cells in hepatocellular carcinoma
    Wong MM, Chan HY, Aziz NA, Ramasamy TS, Bong JJ, Ch'ng ES, et al.
    Mol Biol Rep, 2021 Apr;48(4):3695-3717.
    PMID: 33893928 DOI: 10.1007/s11033-021-06334-9
    Liver cancer is the sixth most common cancer and the fourth leading cause of cancer deaths in the world. The most common type of liver cancers is hepatocellular carcinoma (HCC). Autophagy is the cellular digestion of harmful components by sequestering the waste products into autophagosomes followed by lysosomal degradation for the maintenance of cellular homeostasis. The impairment of autophagy is highly associated with the development and progression of HCC although autophagy may be involved in tumour-suppressing cellular events. In regards to its protecting role, autophagy also shelters the cells from anoikis- a programmed cell death in anchorage-dependent cells detached from the surrounding extracellular matrix which facilitates metastasis in HCC. Liver cancer stem cells (LCSCs) have the ability for self-renewal and differentiation and are associated with the development and progression of HCC by regulating stemness, resistance and angiogenesis. Interestingly, autophagy is also known to regulate normal stem cells by promoting cellular survival and differentiation and maintaining cellular homeostasis. In this review, we discuss the basal autophagic mechanisms and double-faceted roles of autophagy as both tumour suppressor and tumour promoter in HCC, as well as its association with and contribution to self-renewal and differentiation of LCSCs.
    Matched MeSH terms: Neoplastic Stem Cells/metabolism*
  19. The Advancement of Biomaterials in Regulating Stem Cell Fate
    Hiew VV, Simat SFB, Teoh PL
    Stem Cell Rev Rep, 2018 Feb;14(1):43-57.
    PMID: 28884292 DOI: 10.1007/s12015-017-9764-y
    Stem cells are well-known to have prominent roles in tissue engineering applications. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can differentiate into every cell type in the body while adult stem cells such as mesenchymal stem cells (MSCs) can be isolated from various sources. Nevertheless, an utmost limitation in harnessing stem cells for tissue engineering is the supply of cells. The advances in biomaterial technology allows the establishment of ex vivo expansion systems to overcome this bottleneck. The progress of various scaffold fabrication could direct stem cell fate decisions including cell proliferation and differentiation into specific lineages in vitro. Stem cell biology and biomaterial technology promote synergistic effect on stem cell-based regenerative therapies. Therefore, understanding the interaction of stem cell and biomaterials would allow the designation of new biomaterials for future clinical therapeutic applications for tissue regeneration. This review focuses mainly on the advances of natural and synthetic biomaterials in regulating stem cell fate decisions. We have also briefly discussed how biological and biophysical properties of biomaterials including wettability, chemical functionality, biodegradability and stiffness play their roles.
    Matched MeSH terms: Induced Pluripotent Stem Cells/metabolism
  20. Human mesenchymal stem cells promote CD34+hematopoietic stem cell proliferation with preserved red blood cell differentiation capacity
    Lau SX, Leong YY, Ng WH, Ng AWP, Ismail IS, Yusoff NM, et al.
    Cell Biol Int, 2017 Jun;41(6):697-704.
    PMID: 28403524 DOI: 10.1002/cbin.10774
    Studies showed that co-transplantation of mesenchymal stem cells (MSCs) and cord blood-derived CD34+hematopoietic stem cells (HSCs) offered greater therapeutic effects but little is known regarding the effects of human Wharton's jelly derived MSCs on HSC expansion and red blood cell (RBC) generation in vitro. This study aimed to investigate the effects of MSCs on HSC expansion and differentiation. HSCs were co-cultured with MSCs or with 10% MSCs-derived conditioned medium, with HSCs cultured under standard medium served as a control. Cell expansion rates, number of mononuclear cell post-expansion and number of enucleated cells post-differentiation were evaluated. HSCs showed superior proliferation in the presence of MSC with mean expansion rate of 3.5 × 108 ± 1.8 × 107after day 7 compared to the conditioned medium and the control group (8.9 × 107 ± 1.1 × 108and 7.0 × 107 ± 3.3 × 106respectively, P 
    Matched MeSH terms: Hematopoietic Stem Cells/metabolism
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