Displaying publications 1 - 20 of 45 in total

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  1. 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/cytology*; Induced Pluripotent Stem Cells/metabolism
  2. Generation of induced pluripotent stem cells by a polycistronic lentiviral vector in feeder- and serum- free defined culture
    Al Abbar A, Nordin N, Ghazalli N, Abdullah S
    Tissue Cell, 2018 Dec;55:13-24.
    PMID: 30503056 DOI: 10.1016/j.tice.2018.09.004
    Induced pluripotent stem cells (iPSCs) have great potentials for regenerative medicine. However, serious concerns such as the use of the viral-mediated reprogramming strategies and exposure of iPSCs to animal products from feeder cells and serum-containing medium have restricted the application of iPSCs in the clinics. Therefore, the generation of iPSCs with minimal viral integrations and in non-animal sourced and serum-free medium is necessary. In this report, a polycistronic lentiviral vector carrying Yamanaka's factors was used to reprogram mouse fibroblasts into iPSCs in feeder- and xeno-free culture environment. The generated iPSCs exhibited morphology and self-renewal properties of embryonic stem cells (ESCs), expression of specific pluripotent markers, and potentials to differentiate into the three-major distinct specialized germ layers in vitro. The iPSCs were also shown to have the potential to differentiate into neural precursor and neurons in culture, with greater than 95% expression of nestin, Pax6 and βIII-tubulin. This body of work describes an alternative method of generating iPSCs by using polycistronic lentiviral vector that may minimize the risks associated with viral vector-mediated reprogramming and animal derived products in the culture media.
    Matched MeSH terms: Induced Pluripotent Stem Cells/cytology*
  3. Current developments and therapeutic potentials of exosomes from induced pluripotent stem cells-derived mesenchymal stem cells
    Aldoghachi AF, Loh JK, Wang ML, Yang YP, Chien CS, Teh HX, et al.
    J Chin Med Assoc, 2023 Apr 01;86(4):356-365.
    PMID: 36762931 DOI: 10.1097/JCMA.0000000000000899
    Mesenchymal stem cells (MSCs) are multipotent cells derived from adult human tissues that have the ability to proliferate in vitro and maintain their multipotency, making them attractive cell sources for regenerative medicine. However, MSCs reportedly show limited proliferative capacity with inconsistent therapeutic outcomes due to their heterogeneous nature. On the other hand, induced pluripotent stem cells (iPSC) have emerged as an alternative source for the production of various specialized cell types via their ability to differentiate from all three primary germ layers, leading to applications in regenerative medicine, disease modeling, and drug therapy. Notably, iPSCs can differentiate into MSCs in monolayer, commonly referred to as induced mesenchymal stem cells (iMSCs). These cells show superior therapeutic qualities compared with adult MSCs as the applications of the latter are restricted by passage number and autoimmune rejection when applied in tissue regeneration trials. Furthermore, increasing evidence shows that the therapeutic properties of stem cells are a consequence of the paracrine effects mediated by their secretome such as from exosomes, a type of extracellular vesicle secreted by most cell types. Several studies that investigated the potential of exosomes in regenerative medicine and therapy have revealed promising results. Therefore, this review focuses on the recent findings of exosomes secreted from iMSCs as a potential noncell-based therapy.
    Matched MeSH terms: Induced Pluripotent Stem Cells*
  4. Lack of methylation on transgene leads to high level and persistent transgene expression in induced pluripotent stem cells
    Alhaji SY, Nordin N, Ngai SC, Al Abbar A, Mei L, Abdullah S
    Gene, 2020 Oct 20;758:144958.
    PMID: 32683073 DOI: 10.1016/j.gene.2020.144958
    Short-lived therapeutic gene expression in mammalian cells by DNA methylation is one of the major challenges in gene therapy. In this study, we assessed the implication of DNA methylation on the duration of GFP expression in mouse embryonic stem (ES) and mouse induced pluripotent stem (iPS) cells. The cells were transduced with lentivirus (LV) carrying green fluorescent protein (GFP) driven by either human elongation factor (EF1α) or cytomegalovirus (CMV) promoter. Transduced iPS cells exhibited higher percentage of GFP+ cells with persistent mean fluorescent intensity than transduced ES cells. Analysis on the integrated copy of transgene in the population of the transduced cells demonstrated similar copy number. However, significant increase in GFP intensity following 5-azaC treatment was observed in transduced ES cells only, suggesting the influence of DNA methylation in transgene silencing. Subsequent DNA methylation analysis showed that the promoter and the GFP region of the provirus in iPS cells had negligible methylation profile compared to transduced ES cells. Interestingly, sustained transgene expression was observed upon directed differentiation of transduced iPS cells towards CD34+ CD45+ cells. Hence, this study has shown that favourable transgene activity from lentiviral transduced iPS cells was due to the lack of methylation at the proviral regions.
    Matched MeSH terms: Induced Pluripotent Stem Cells/metabolism*
  5. Fulltext Stem cells research: therapeutic potentials and ethical issues from Islamic perspective
    Che Anuar Che Mohamad, Abdurezak Abdullahi Hashi
    International Medical Journal Malaysia, 2018;17(101):65-69.
    MyJurnal
    The advancement in human stem cell research has promised a viable alternative treatment for a range of ‘incurable diseases’ such as neurological diseases. To date, several studies have documented substantial evidences on the therapeutic properties of stem cells in promoting repair in different diseases including common neurological disorders i.e. ischaemic stroke and spinal cord injury. However, the progress of stem cell research has been surrounded by ethical issues which largely due to the usage of human embryos as one of the sources. These embryonic stem cells which originally derived from human embryo of aborted foetus or already existing human embryonic stem cells (hESCs) lines, has sparked an intense moral and religious argument among people of various faith, including Muslim community. From the therapeutic point of view, amongst the currently available stem cells, hESCs show the greatest potential for the broadest range of cell replacement therapies and are regarded as the most commercially viable. This review focuses on the major ethical issues, particularly to Muslim community, related to human embryonic stem cells research with special emphasis on the moral status of the embryo and the beginning of life according to the Islamic ethics and rulings. In this paper, we also discuss some ethical positions towards embryonic stem cell research in the Islamic world, including official regulations existing in some Muslim countries. We examine the justification and the necessity on the usage of hESCs following the newly discovered Induced Pluripotent Stem Cells (IPSCs) in the laboratory. In addition, we supplement the discussions with the general views and positions from the other two Abrahamic religions i.e. Christianity and Judaism.
    Matched MeSH terms: Induced Pluripotent Stem Cells
  6. Generation of a MLL-AF9-specific stem cell model of acute monocytic leukemia
    Chiew MY, Boo NY, Voon K, Cheong SK, Leong PP
    Leuk Lymphoma, 2017 01;58(1):162-170.
    PMID: 27185517
    Acute monocytic leukemia (AML-M5), a subtype of acute myeloid leukemia (AML), affects mostly young children and has poor prognosis. The mechanisms of treatment failure of AML-M5 are still unclear. In this study, we generated iPSC from THP-1 cells from a patient with AML-M5, using retroviruses encoding the pluripotency-associated genes (OCT3/4, SOX2, KLF4 and c-MYC). These AML-M5-derived iPSC showed features similar with those of human embryonic stem cells in terms of the morphology, gene expression, protein/antigen expression and differentiation capability. Parental-specific markers were down-regulated in these AML-M5-derived iPSCs. Expression of MLL-AF9 fusion gene (previously identified to be associated with pathogenesis of AML-M5) was observed in all iPSC clones as well as parental cells. We conclude that AML-M5-specific iPSC clones have been successfully developed. This disease model may provide a novel approach for future study of pathogenesis and therapeutic intervention of AML-M5.
    Matched MeSH terms: Induced Pluripotent Stem Cells/metabolism
  7. Current trends and promising clinical utility of IPSC-derived MSC (iMSC)
    Chiou SH, Ong HKA, Chou SJ, Aldoghachi AF, Loh JK, Verusingam ND, et al.
    Prog Mol Biol Transl Sci, 2023;199:131-154.
    PMID: 37678969 DOI: 10.1016/bs.pmbts.2023.04.002
    Mesenchymal stem cells (MSCs) differentiated from human induced pluripotent stem cells (iPSC) or induced MSC (iMSCs) are expected to address issues of scalability and safety as well as the difficulty in producing homogenous clinical grade MSCs as demonstrated by the promising outcomes from preclinical and clinical trials, currently ongoing. The assessment of iMSCs based in vitro and in vivo studies have thus far showed more superior performance as compared to that of the primary or native human MSCs, in terms of cell proliferation, expansion capacity, immunomodulation properties as well as the influence of paracrine signaling and exosomal influence in cell-cell interaction. In this chapter, an overview of current well-established methods in generating a sustainable source of iMSCs involving well defined culture media is discussed followed by the properties of iMSC as compared to that of MSC and its promising prospects for continuous development into potential clinical grade applications.
    Matched MeSH terms: Induced Pluripotent Stem Cells*
  8. PAMAM dendrimer roles in gene delivery methods and stem cell research
    Daneshvar N, Abdullah R, Shamsabadi FT, How CW, Mh MA, Mehrbod P
    Cell Biol Int, 2013 May;37(5):415-9.
    PMID: 23504853 DOI: 10.1002/cbin.10051
    Nanotechnology has provided new technological opportunities, which could help in challenges confronting stem cell research. Polyamidoamine (PAMAM) dendrimers, a new class of macromolecular polymers with high molecular uniformity, narrow molecular distribution specific size and shape and highly functionalised terminal surface have been extensively explored for biomedical application. PAMAM dendrimers are also nanospherical, hyperbranched and monodispersive molecules exhibiting exclusive properties which make them potential carriers for drug and gene delivery.
    Matched MeSH terms: Induced Pluripotent Stem Cells/cytology; Induced Pluripotent Stem Cells/metabolism
  9. Induced pluripotent stem cells (iPSCs): the emergence of a new champion in stem cell technology-driven biomedical applications
    Das AK, Pal R
    J Tissue Eng Regen Med, 2010 Aug;4(6):413-21.
    PMID: 20084623 DOI: 10.1002/term.258
    Pluripotent stem cells possess the unique property of differentiating into all other cell types of the human body. Further, the discovery of induced pluripotent stem cells (iPSCs) in 2006 has opened up new avenues in clinical medicine. In simple language, iPSCs are nothing but somatic cells reprogrammed genetically to exhibit pluripotent characteristics. This process utilizes retroviruses/lentiviruses/adenovirus/plasmids to incorporate candidate genes into somatic cells isolated from any part of the human body. It is also possible to develop disease-specific iPSCs which are most likely to revolutionize research in respect to the pathophysiology of most debilitating diseases, as these can be mimicked ex vivo in the laboratory. These models can also be used to study the safety and efficacy of known drugs or potential drug candidates for a particular diseased condition, limiting the need for animal studies and considerably reducing the time and money required to develop new drugs. Recently, functional neurons, cardiomyocytes, pancreatic islet cells, hepatocytes and retinal cells have been derived from human iPSCs, thus re-confirming the pluripotency and differentiation capacity of these cells. These findings further open up the possibility of using iPSCs in cell replacement therapy for various degenerative disorders. In this review we highlight the development of iPSCs by different methods, their biological characteristics and their prospective applications in regenerative medicine and drug screening. We further discuss some practical limitations pertaining to this technology and how they can be averted for the betterment of human life.
    Matched MeSH terms: Induced Pluripotent Stem Cells/cytology*; Induced Pluripotent Stem Cells/metabolism
  10. Fulltext Clinical Potential of Cellular Material Sources in the Generation of iPSC-Based Products for the Regeneration of Articular Cartilage
    Eremeev A, Pikina A, Ruchko Y, Bogomazova A
    Int J Mol Sci, 2023 Sep 22;24(19).
    PMID: 37833856 DOI: 10.3390/ijms241914408
    Inflammatory joint diseases, among which osteoarthritis and rheumatoid arthritis are the most common, are characterized by progressive degeneration of the cartilage tissue, resulting in the threat of limited or lost joint functionality in the absence of treatment. Currently, treating these diseases is difficult, and a number of existing treatment and prevention measures are not entirely effective and are complicated by the patients' conditions, the multifactorial nature of the pathology, and an incomplete understanding of the etiology. Cellular technologies based on induced pluripotent stem cells (iPSCs) can provide a vast cellular resource for the production of artificial cartilage tissue for replacement therapy and allow the possibility of a personalized approach. However, the question remains whether a number of etiological abnormalities associated with joint disease are transmitted from the source cell to iPSCs and their chondrocyte derivatives. Some data state that there is no difference between the iPSCs and their derivatives from healthy and sick donors; however, there are other data indicating a dissimilarity. Therefore, this topic requires a thorough study of the differentiation potential of iPSCs and the factors influencing it, the risk factors associated with joint diseases, and a comparative analysis of the characteristics of cells obtained from patients. Together with cultivation optimization methods, these measures can increase the efficiency of obtaining cell technology products and make their wide practical application possible.
    Matched MeSH terms: Induced Pluripotent Stem Cells*
  11. Fulltext Generation of the induced pluripotent stem cell (hiPSC) line (JUFMDOi004-A) from a patient with hearing loss carrying GJB2 (p.V37I) mutation
    Fukunaga I, Shiga T, Chen C, Oe Y, Danzaki K, Ohta S, et al.
    Stem Cell Res, 2020 03;43:101674.
    PMID: 31926383 DOI: 10.1016/j.scr.2019.101674
    The gap junction beta-2 (GJB2) gene is the most common genetic cause of hereditary deafness worldwide. Especially, V37I mutation in GJB2 is most prevalent in Southeast Asia including Thailand, Malaysia, and Indonesia. Furthermore, it is the second most prevalent cause in Japan and China, and exhibits an audiometric phenotype of mild-to-moderate hearing loss. In this study, we generated induced pluripotent stem cells (iPSC) from peripheral blood mononuclear cells (PBMCs) of patient with homozygous V37I mutation. This iPSC line will be a powerful tool for investigating the pathogenesis and for developing a treatment for GJB2-related hearing loss.
    Matched MeSH terms: Induced Pluripotent Stem Cells/metabolism*
  12. A plethora of human pluripotent stem cells
    Gao L, Thilakavathy K, Nordin N
    Cell Biol Int, 2013 Sep;37(9):875-87.
    PMID: 23619972 DOI: 10.1002/cbin.10120
    At the early stages of mammalian development, a number of developmentally plastic cells appear that possess the ability to give rise to all of the differentiated cell types normally derived from the three primary germ layers - unique character known as pluripotency. To date, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to be truly pluripotent. However, recent studies have revealed a variety of other cells that demonstrate pluripotentiality, including very small embryonic-like stem cells (VSELs), amniotic fluid stem cells (AFSCs), marrow-isolated adult multilineage inducible cells (MIAMI) and multipotent adult precursor cells (MAPCs). This review summarises key features of these six kinds of pluripotent and potentially pluripotent stem cells (ESCs, iPSCs, VSELs, AFSCs, MIAMI and MAPCs) and the evidence for their pluripotency properties.
    Matched MeSH terms: Induced Pluripotent Stem Cells/cytology*; Induced Pluripotent Stem Cells/metabolism
  13. Fulltext Incomplete cellular reprogramming of colorectal cancer cells elicits an epithelial/mesenchymal hybrid phenotype
    Hiew MSY, Cheng HP, Huang CJ, Chong KY, Cheong SK, Choo KB, et al.
    J Biomed Sci, 2018 Jul 19;25(1):57.
    PMID: 30025541 DOI: 10.1186/s12929-018-0461-1
    BACKGROUND: Induced pluripotency in cancer cells by ectopic expression of pluripotency-regulating factors may be used for disease modeling of cancers. MicroRNAs (miRNAs) are negative regulators of gene expression that play important role in reprogramming somatic cells. However, studies on the miRNA expression profile and the expression patterns of the mesenchymal-epithelial transition (MET)/epithelial-mesenchymal transition (EMT) genes in induced pluripotent cancer (iPC) cells are lacking.

    METHODS: iPC clones were generated from two colorectal cancer (CRC) cell lines by retroviral transduction of the Yamanaka factors. The iPC clones obtained were characterized by morphology, expression of pluripotency markers and the ability to undergo in vitro tri-lineage differentiation. Genome-wide miRNA profiles of the iPC cells were obtained by microarray analysis and bioinformatics interrogation. Gene expression was done by real-time RT-PCR and immuno-staining; MET/EMT protein levels were determined by western blot analysis.

    RESULTS: The CRC-iPC cells showed embryonic stem cell-like features and tri-lineage differentiation abilities. The spontaneously-differentiated post-iPC cells obtained were highly similar to the parental CRC cells. However, down-regulated pluripotency gene expression and failure to form teratoma indicated that the CRC-iPC cells had only attained partial pluripotency. The CRC-iPC cells shared similarities in the genome-wide miRNA expression profiles of both cancer and pluripotent embryonic stem cells. One hundred and two differentially-expressed miRNAs were identified in the CRC-iPC cells, which were predicted by bioinformatics analysis be closely involved in regulating cellular pluripotency and the expression of the MET/EMT genes, possibly via the phosphatidylinositol-3 kinases-protein kinase B (PI3K-Akt) and transforming growth factor beta (TGF-β) signaling pathways. Irregular and inconsistent expression patterns of the EMT vimentin and Snai1 and MET E-cadherin and occludin proteins were observed in the four CRC-iPC clones analyzed, which suggested an epithelial/mesenchymal hybrid phenotype in the partially reprogrammed CRC cells. MET/EMT gene expression was also generally reversed on re-differentiation, also suggesting epigenetic regulation.

    CONCLUSIONS: Our data support the elite model for cancer cell-reprogramming in which only a selected subset of cancer may be fully reprogrammed; partial cancer cell reprogramming may also elicit an epithelial-mesenchymal mixed phenotype, and highlight opportunities and challenges in cancer cell-reprogramming.

    Matched MeSH terms: Induced Pluripotent Stem Cells/metabolism; Induced Pluripotent Stem Cells/pathology
  14. 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
  15. Fulltext Frequent co-expression of miRNA-5p and -3p species and cross-targeting in induced pluripotent stem cells
    Huang CJ, Nguyen PN, Choo KB, Sugii S, Wee K, Cheong SK, et al.
    Int J Med Sci, 2014;11(8):824-33.
    PMID: 24936146 DOI: 10.7150/ijms.8358
    A miRNA precursor generally gives rise to one major miRNA species derived from the 5' arm, and are called miRNA-5p. However, more recent studies have shown co-expression of miRNA-5p and -3p, albeit in different concentrations, in cancer cells targeting different sets of transcripts. Co-expression and regulation of the -5p and -3p miRNA species in stem cells, particularly in the reprogramming process, have not been studied.
    Matched MeSH terms: Induced Pluripotent Stem Cells/metabolism*
  16. Advances in the Generation of Functional β-cells from Induced Pluripotent Stem Cells As a Cure for Diabetes Mellitus
    Kalra K, Chandrabose ST, Ramasamy TS, Kasim NHBA
    Curr Drug Targets, 2018;19(13):1463-1477.
    PMID: 29874998 DOI: 10.2174/1389450119666180605112917
    Diabetes mellitus is one of the leading causes of death worldwide. Loss and functional failure of pancreatic β-cells, the parenchyma cells in the islets of Langerhans, progress diabetes mellitus. The increasing incidence of this metabolic disorder necessitates efficient strategies to produce functional β-cells for treating diabetes mellitus. Human induced Pluripotent Stem Cells (hiPSC), hold potential for treating diabetes ownig to their self-renewal capacity and the ability to differentiate into β- cells. iPSC technology also provides unlimited starting material to generate differentiated cells for regenerative applications. Progress has also been made in establishing in-vitro culture protocols to yield definitive endoderm, pancreatic endoderm progenitor cells and β-cells via different reprogramming strategies and growth factor supplementation. However, these generated β-cells are still immature, lack functional characteristics and exhibit lower capability in reversing the diseases conditions. Current methods employed to generate mature and functional β-cells include; use of small and large molecules to enhance the reprogramming and differentiation efficiency, 3D culture systems to improve the functional properties and heterogeneity of differentiated cells. This review details recent advancements in the generation of mature β-cells by reprogramming stem cells into iPSCs that are further programmed to β-cells. It also provides deeper insight into current reprogramming protocols and their efficacy, focusing on the underlying mechanism of chemical-based approach to generate iPSCs. Furthermore, we have highlighted the recent differentiation strategies both in-vitro and in-vivo to date and the future prospects in the generation of mature β-cells.
    Matched MeSH terms: Induced Pluripotent Stem Cells/cytology*
  17. Retention of Somatic Memory Associated with Cell Identity, Age and Metabolism in Induced Pluripotent Stem (iPS) Cells Reprogramming
    Khoo TS, Jamal R, Abdul Ghani NA, Alauddin H, Hussin NH, Abdul Murad NA
    Stem Cell Rev Rep, 2020 04;16(2):251-261.
    PMID: 32016780 DOI: 10.1007/s12015-020-09956-x
    The discovery of induced pluripotent stem (iPS) cells in 2006 marked a major breakthrough in regenerative medicine, enabling reversal of terminally differentiated somatic cells into pluripotent stem cells. The embryonic stem (ES) cells-like pluripotency and unlimited self-renewal capability of iPS cells have granted them enormous potential in many applications, particularly regenerative therapy. Unlike ES cells, however, iPS cells exhibit somatic memories which were carried over from the tissue of origin thus limited its translation in clinical applications. This review provides an updated overview of the retention of various somatic memories associated with the cellular identity, age and metabolism of tissue of origin in iPS cells. The influence of cell types, stage of maturation, age and various other factors on the retention of somatic memory has been discussed. Recent evidence of somatic memory in the form of epigenetic, transcriptomic, metabolic signatures and its functional manifestations in both in vitro and in vivo settings also have been reviewed. The increasing number of studies which had adopted isogenic cell lines for comparisons in recent years had facilitated the identification of genuine somatic memories. These memories functionally affect iPS cells and its derivatives and are potentially tumorigenic thus, raising concerns on their safety in clinical application. Various approaches for memory erasure had since being reported and their efficacies were highlighted in this review.
    Matched MeSH terms: Induced Pluripotent Stem Cells/cytology*; Induced Pluripotent Stem Cells/metabolism*
  18. Fulltext Recent developments in β-cell differentiation of pluripotent stem cells induced by small and large molecules
    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: Induced Pluripotent Stem Cells
  19. Fulltext Advancements in reprogramming strategies for the generation of induced pluripotent stem cells
    Lai MI, Wendy-Yeo WY, Ramasamy R, Nordin N, Rosli R, Veerakumarasivam A, et al.
    J Assist Reprod Genet, 2011 Apr;28(4):291-301.
    PMID: 21384252 DOI: 10.1007/s10815-011-9552-6
    Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells has emerged as an invaluable method for generating patient-specific stem cells of any lineage without the use of embryonic materials. Following the first reported generation of iPS cells from murine fibroblasts using retroviral transduction of a defined set of transcription factors, various new strategies have been developed to improve and refine the reprogramming technology. Recent developments provide optimism that the generation of safe iPS cells without any genomic modification could be derived in the near future for the use in clinical settings. This review summarizes current and evolving strategies in the generation of iPS cells, including types of somatic cells for reprogramming, variations of reprogramming genes, reprogramming methods, and how the advancement iPS cells technology can lead to the future success of reproductive medicine.
    Matched MeSH terms: Induced Pluripotent Stem Cells/cytology*
  20. Fulltext Tumor Necrosis Factor-Alpha Exacerbates Viral Entry in SARS-CoV2-Infected iPSC-Derived Cardiomyocytes
    Lee CY, Huang CH, Rastegari E, Rengganaten V, Liu PC, Tsai PH, et al.
    Int J Mol Sci, 2021 Sep 13;22(18).
    PMID: 34576032 DOI: 10.3390/ijms22189869
    The coronavirus disease 2019 (COVID-19) pandemic with high infectivity and mortality has caused severe social and economic impacts worldwide. Growing reports of COVID-19 patients with multi-organ damage indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may also disturb the cardiovascular system. Herein, we used human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) as the in vitro platform to examine the consequence of SARS-CoV2 infection on iCMs. Differentiated iCMs expressed the primary SARS-CoV2 receptor angiotensin-converting enzyme-II (ACE2) and the transmembrane protease serine type 2 (TMPRSS2) receptor suggesting the susceptibility of iCMs to SARS-CoV2. Following the infection of iCMs with SARS-CoV2, the viral nucleocapsid (N) protein was detected in the host cells, demonstrating the successful infection. Bioinformatics analysis revealed that the SARS-CoV2 infection upregulates several inflammation-related genes, including the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The pretreatment of iCMs with TNF-α for 24 h, significantly increased the expression of ACE2 and TMPRSS2, SASR-CoV2 entry receptors. The TNF-α pretreatment enhanced the entry of GFP-expressing SARS-CoV2 pseudovirus into iCMs, and the neutralization of TNF-α ameliorated the TNF-α-enhanced viral entry. Collectively, SARS-CoV2 elevated TNF-α expression, which in turn enhanced the SARS-CoV2 viral entry. Our findings suggest that, TNF-α may participate in the cytokine storm and aggravate the myocardial damage in COVID-19 patients.
    Matched MeSH terms: Induced Pluripotent Stem Cells
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