Displaying publications 41 - 60 of 412 in total

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  1. 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*
  2. 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*
  3. Pagliuca S, Gurnari C, Hercus C, Hergalant S, Nadarajah N, Wahida A, et al.
    Leukemia, 2023 Jan;37(1):202-211.
    PMID: 36253429 DOI: 10.1038/s41375-022-01723-w
    Idiopathic aplastic anemia (IAA) pathophysiology is dominated by autoreactivity of human leukocyte antigen (HLA)-restricted T-cells against antigens presented by hematopoietic stem and progenitor cells (HSPCs). Expansion of PIGA and HLA class I mutant HSPCs have been linked to immune evasion from T-cell mediated pressures. We hypothesized that in analogy with antitumor immunity, the pathophysiological cascade of immune escape in IAA is initiated by immunoediting pressures and culminates with mechanisms of clonal evolution characterized by hits in immune recognition and response genes. To that end, we studied the genetic and transcriptomic make-up of the antigen presentation complexes in a large cohort of patients with IAA and paroxysmal nocturnal hemoglobinuria (PNH) by using single-cell RNA, high throughput DNA sequencing and single nucleotide polymorphism (SNP)-array platforms. At disease onset, HSPCs displayed activation of selected HLA class I and II-restricted mechanisms, without extensive inhibition of immune checkpoint apparatus. Using a newly implemented bioinformatic framework we found that not only class I but also class II genes were often impaired by acquisition of genetic aberrations. We also demonstrated the presence of novel somatic alterations in immune genes possibly contributing to the evasion from the autoimmune T-cells. In contrast, these hits were absent in myeloid neoplasia. These aberrations were not mutually exclusive with PNH and did not correlate with the accumulation of myeloid-driver hits. Our findings shed light on the mechanisms of immune activation and escape in IAA and define alternative modes of clonal hematopoiesis.
    Matched MeSH terms: Hematopoietic Stem Cells/pathology
  4. Pandrangi SL, Chittineedi P, Chalumuri SS, Meena AS, Neira Mosquera JA, Sánchez Llaguno SN, et al.
    Molecules, 2022 May 07;27(9).
    PMID: 35566360 DOI: 10.3390/molecules27093011
    Iron is a crucial element required for the proper functioning of the body. For instance, hemoglobin is the vital component in the blood that delivers oxygen to various parts of the body. The heme protein present in hemoglobin comprises iron in the form of a ferrous state which regulates oxygen delivery. Excess iron in the body is stored as ferritin and would be utilized under iron-deficient conditions. Surprisingly, cancer cells as well as cancer stem cells have elevated ferritin levels suggesting that iron plays a vital role in protecting these cells. However, apart from the cytoprotective role iron also has the potential to induce cell death via ferroptosis which is a non-apoptotic cell death dependent on iron reserves. Apoptosis a caspase-dependent cell death mechanism is effective on cancer cells however little is known about its impact on cancer stem cell death. This paper focuses on the molecular characteristics of apoptosis and ferroptosis and the importance of switching to ferroptosis to target cancer stem cells death thereby preventing cancer relapse. To the best of our knowledge, this is the first review to demonstrate the importance of intracellular iron in regulating the switching of tumor cells and therapy resistant CSCs from apoptosis to ferroptosis.
    Matched MeSH terms: Neoplastic Stem Cells/metabolism
  5. Mohd Nor NH, Mansor NI, Mohd Kashim MIA, Mokhtar MH, Mohd Hatta FA
    Int J Mol Sci, 2023 Jul 21;24(14).
    PMID: 37511524 DOI: 10.3390/ijms241411763
    Stem cells derived from human exfoliated deciduous teeth (SHED) have emerged as an alternative stem cell source for cell therapy and regenerative medicine because they are readily available, pose fewer ethical concerns, and have low immunogenicity and tumourigenicity. SHED offer a number of advantages over other dental stem cells, including a high proliferation rate with the potential to differentiate into multiple developmental lineages. The therapeutic effects of SHED are mediated by multiple mechanisms, including immunomodulation, angiogenesis, neurogenesis, osteogenesis, and adipogenesis. In recent years, there is ample evidence that the mechanism of action of SHED is mainly due to its paracrine action, releasing a wide range of soluble factors such as cytokines, chemokines, and trophic factors (also known as 'secretome') into the local tissue microenvironment to promote tissue survival and recovery. This review provides an overview of the secretome derived from SHED and highlights the bioactive molecules involved in tissue regeneration and their potential applications in regenerative medicine.
    Matched MeSH terms: Stem Cells*
  6. Govindasamy V, Abdullah AN, Ronald VS, Musa S, Ab Aziz ZA, Zain RB, et al.
    J Endod, 2010 Sep;36(9):1504-15.
    PMID: 20728718 DOI: 10.1016/j.joen.2010.05.006
    Lately, several new stem cell sources and their effective isolation have been reported that claim to have potential for therapeutic applications. However, it is not yet clear which type of stem cell sources are most potent and best for targeted therapy. Lack of understanding of nature of these cells and their lineage-specific propensity might hinder their full potential. Therefore, understanding the gene expression profile that indicates their lineage-specific proclivity is fundamental to the development of successful cell-based therapies.
    Matched MeSH terms: Stem Cells/classification*; Stem Cells/cytology; Stem Cells/physiology; Pluripotent Stem Cells/cytology; Pluripotent Stem Cells/physiology; Adult Stem Cells/classification; Adult Stem Cells/cytology; Adult Stem Cells/physiology
  7. 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: Embryonic Stem Cells/metabolism*; Induced Pluripotent Stem Cells/metabolism*
  8. Kumar DH, Kutty MK
    Indian J Pathol Microbiol, 2012 Apr-Jun;55(2):147-53.
    PMID: 22771633 DOI: 10.4103/0377-4929.97842
    Cancer is fundamentally a cellular genetic disease capable of transferring the "disease" to the next generation of mutated cells. Similar proliferative and information transferring capacity exists in the stem cells of various organ systems in the human body. Understanding the bio-mechanism of stem cell metabolism and its regulation by signaling molecules and extracellular micro-environment is an important step toward successful prevention and treatment of cancer. According to the cancer stem cell hypothesis, both hereditary and sporadic cancers can arise from deregulation of these cancer stem cells (CSCs), triggered by genetic and environmental factors. It is shown that deregulation of normal self-renewal pathways in undifferentiated breast stem cells or progenitor cells had altered mammary system or progenitor cells, resulting in abnormally differentiated cells in human and rodent breast cancer cell lines. Breakthroughs in molecular pathways have important therapeutic implications. Hence, significant stress is laid on targeting signaling molecules and their micromilieu in breast cancer therapy.
    Matched MeSH terms: Stem Cells/cytology*; Neoplastic Stem Cells/pathology*
  9. Dutta S, Singh G, Sreejith S, Mamidi MK, Husin JM, Datta I, et al.
    CNS Neurosci Ther, 2013 Jan;19(1):5-11.
    PMID: 23253099 DOI: 10.1111/cns.12027
    Neurodegenerative diseases are devastating because they cause increasing loss of cognitive and physical functions and affect an estimated 1 billion individuals worldwide. Unfortunately, no drugs are currently available to halt their progression, except a few that are largely inadequate. This mandates the search of new treatments for these progressively degenerative diseases. Neural stem cells (NSCs) have been successfully isolated, propagated, and characterized from the adult brains of mammals, including humans. The confirmation that neurogenesis occurs in the adult brain via NSCs opens up fresh avenues for treating neurological problems. The proof-of-concept studies demonstrating the neural differentiation capacity of stem cells both in vitro and in vivo have raised widespread enthusiasm toward cell-based interventions. It is anticipated that cell-based neurogenic drugs may reverse or compensate for deficits associated with neurological diseases. The increasing interest of the private sector in using human stem cells in therapeutics is evidenced by launching of several collaborative clinical research activities between Pharma giants and research institutions or small start-up companies. In this review, we discuss the major developments that have taken place in this field to position stem cells as a prospective candidate drug for the treatment of neurological disorders.
    Matched MeSH terms: Pluripotent Stem Cells/physiology; Neural Stem Cells/physiology
  10. 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: Embryonic Stem Cells/cytology*; Induced Pluripotent Stem Cells/cytology*
  11. Nishakanthi G
    Asian Bioeth Rev, 2019 Dec;11(4):437-460.
    PMID: 33717327 DOI: 10.1007/s41649-019-00102-5
    Ethics is a philosophical branch of inquiry that reasons between what is right and wrong. The moral philosophy of Socrates, Aristotle, and Plato from ancient Greek became the basis of most of the western ethics. These days, ethics can be divided based on its inquiries for example, normative, descriptive, metaethics, and applied ethics or based on its theories like utilitarianism, emotivism, and universal ethics. In context with applied ethics that examines issues involving emerging technologies, this study will look into the ethics of Malaysian stem cell technology based on written literature. It was mainly to identify Malaysian literature on stem cell ethics through conventional search since the mainstream international database indicated an obvious shortage. The critical review of this literature will facilitate in the understanding of unique position of Malaysia towards stem cell and its ethics in reference to the limited number. Despite the limitation, this can be a preliminary study urging for more inquiries and exploration to fulfil the multiple perspectives in ethics such as the diversity of Malaysian ethics, the impact of ethics in stem cell regulation in Malaysia, and if western contemporary ethics influences Malaysian ethics particularly involving stem cell technology.
    Matched MeSH terms: Stem Cells
  12. Satar Jabbar Rahi Algraittee, Rajesh Ramasamy
    MyJurnal
    Human cartilage contains multipotent stem cells, namely mesenchymal stem cells (MSCs) which are progenitors of connective tissue that play homeostatic and reparative roles. Although the major constituent cells in the cartilage are chondrocytes, they possess a limited regenerative ability, and as a result, spontaneous cartilage repair by chondro- cytes leads to the synthesis of fibrocartilage. Similarly, MSCs derived from articular cartilage of osteoarthritis patients have demonstrated inadequacy in cartilage repair. The role of MSCs in the pathophysiology of osteoarthritis (OA) is not entirely understood, whether the inflammatory milieu associated with OA joints affects the reparative properties of MSCs or the inherent defects of OA cartilage-derived MSCs impair the proper execution of the required immu- nosuppressive and reparative functions. Therefore, the current review explores the biological characteristics and features of MSCs derived from physiological state and OA condition with the aim of identifying how OA affects MSC functions as well as the role of MSCs in the pathophysiology of OA.

    Matched MeSH terms: Multipotent Stem Cells
  13. Nur Izzati Mansor, Nuratiqah Azmi, Ling, King-Hwa, Rozita Rosli, Zurina Hassan, Norshariza Nordin
    Neuroscience Research Notes, 2019;2(1):16-30.
    MyJurnal
    The use of in vitromodel for screening pharmacological compounds or natural products has gained global interest. The choice of cells to be manipulated plays a vital role in coming up with the best-suitedmodel for specific diseases, including neurodegenerativediseases (ND). A good in vitro ND model should provide appropriate morphological and molecular features that mimic ND conditions where it can be used to screen potential properties of natural products in addition to unravelling the molecular mechanisms of ND. In this mini review, we intend to demonstrate two prospective stem cell lines as the potential cell source for in vitroND model and compare them to the commonly used cells. The common source of cells that have been usedas the in vitroND models is discussedbefore going into details talking about the two prospective stem cell lines.
    Matched MeSH terms: Stem Cells
  14. Agarwal T, Chiesa I, Presutti D, Irawan V, Vajanthri KY, Costantini M, et al.
    Mater Sci Eng C Mater Biol Appl, 2021 Apr;123:112005.
    PMID: 33812625 DOI: 10.1016/j.msec.2021.112005
    Inadequate self-repair and regenerative efficiency of the cartilage tissues has motivated the researchers to devise advanced and effective strategies to resolve this issue. Introduction of bioprinting to tissue engineering has paved the way for fabricating complex biomimetic engineered constructs. In this context, the current review gears off with the discussion of standard and advanced 3D/4D printing technologies and their implications for the repair of different cartilage tissues, namely, articular, meniscal, nasoseptal, auricular, costal, and tracheal cartilage. The review is then directed towards highlighting the current stem cell opportunities. On a concluding note, associated critical issues and prospects for future developments, particularly in this sphere of personalized medicines have been discussed.
    Matched MeSH terms: Stem Cells
  15. Heng WS, Pore M, Meijer C, Hiltermann TJN, Cheah SC, Gosens R, et al.
    Lung Cancer, 2021 04;154:13-22.
    PMID: 33607458 DOI: 10.1016/j.lungcan.2021.02.002
    OBJECTIVES: Cancer stem cells (CSCs) have been implicated in disease progression of aggressive cancers including small cell lung carcinoma (SCLC). Here, we have examined the possible contribution of CSCs to SCLC progression and aggressiveness.

    MATERIALS AND METHODS: GLC-14, GLC-16 and GLC-19 SCLC cell lines derived from one patient, representing increasing progressive stages of disease were used. CSC marker expressions was determined by RT-qPCR and western blotting analyses, and heterogeneity was studied by CSC marker expression by immunofluorescence microscopy and flow cytometry. Colony formation assays were used to assess stem cell properties and therapy sensitivity.

    RESULTS: Increasing expression of stem cell markers MYC, SOX2 and particularly CD44 were found in association with advancing disease. Single and overlapping expression of these markers indicated the presence of different CSC populations. The accumulation of more homogeneous double- and triple-positive CSC populations evolved with disease progression. Functional characterization of CSC properties affirmed higher proficiency of colony forming ability and increased resistance to γ-irradiation in GLC-16 and GLC-19 compared to GLC-14. GLC-19 colony formation was significantly inhibited by a human anti-CD44 antibody.

    CONCLUSION: The progressive increase of MYC, SOX2 and particularly CD44 expression that was accompanied with enhanced colony forming capacity and resistance in the in vitro GLC disease progression model, supports the potential clinical relevance of CSC populations in malignancy and disease relapse of SCLC.

    Matched MeSH terms: Neoplastic Stem Cells
  16. Koh B, Sulaiman N, Fauzi MB, Law JX, Ng MH, Idrus RBH, et al.
    Cell Biosci, 2020;10:75.
    PMID: 32518618 DOI: 10.1186/s13578-020-00438-8
    Stem cell-based regenerative medicine is a promising approach for tissue reconstruction. However, a large number of cells are needed in a typical clinical study, where conventional monolayer cultures might pose a limitation for scale-up. The purpose of this review was to systematically assess the application of microcarriers in Mesenchymal Stem Cell cultures. A comprehensive search was conducted in Medline via Ebscohost, Pubmed, and Scopus, and relevant studies published between 2015 and 2019 were selected. The literature search identified 53 related studies, but only 14 articles met the inclusion criteria. These include 7 utilised commercially available microcarriers, while the rest were formulated based on different surface characteristics, all of which are discussed in this review. Current applications of microcarriers were focused on MSC expansion and induction of MSCs into different lineages. These studies demonstrated that MSCs could proliferate in a microcarrier culture system in-fold compared to monolayer cultures, and the culture system could simulate a three-dimensional environment which induces cell differentiation. However, detailed studies are still required before this system were to be adapted into the scale of GMP manufacturing.
    Matched MeSH terms: Stem Cells
  17. Heng BC, Gong T, Wang S, Lim LW, Wu W, Zhang C
    J Endod, 2017 Mar;43(3):409-416.
    PMID: 28231979 DOI: 10.1016/j.joen.2016.10.033
    INTRODUCTION: Dental follicle stem cells (DFSCs) possess neurogenic potential because they originate from the embryonic neural crest. This study investigated whether neural differentiation of DFSCs can be enhanced by culture on decellularized matrix substrata (NSC-DECM) derived from neurogenesis of human embryonic stem cells (hESCs).

    METHODS: The hESCs were differentiated into neural stem cells (NSCs), and NSC-DECM was extracted from confluent monolayers of NSCs through treatment with deionized water. DFSCs seeded on NSC-DECM, Geltrex, and tissue culture polystyrene (TCPS) were subjected to neural induction during a period of 21 days. Expression of early/intermediate (Musashi1, PAX6, NSE, and βIII-tubulin) and mature/late (NGN2, NeuN, NFM, and MASH1) neural markers by DFSCs was analyzed at the 7-, 14-, and 21-day time points with quantitative real-time polymerase chain reaction. Immunocytochemistry for detection of βIII-tubulin, PAX6, and NGN2 expression by DFSCs on day 7 of neural induction was also carried out.

    RESULTS: Quantitative RT-PCR showed that expression of PAX6, Musashi1, βIII-tubulin, NSE, NGN2, and NFM by DFSCs was enhanced on NSC-DECM versus either the Geltrex or TCPS groups. Immunocytochemistry showed that DFSCs in the NSC-DECM group displayed more intense staining for βIII-tubulin, PAX6, and NGN2 expression, together with more neurite outgrowths and elongated morphology, as compared with either Geltrex or TCPS.

    CONCLUSIONS: DECM derived from neurogenesis of hESCs can enhance the neurogenic potential of DFSCs.

    Matched MeSH terms: Embryonic Stem Cells/cytology*; Neural Stem Cells/physiology*
  18. Wan Safwani WKZ, Choi JR, Yong KW, Ting I, Mat Adenan NA, Pingguan-Murphy B
    Cryobiology, 2017 04;75:91-99.
    PMID: 28108309 DOI: 10.1016/j.cryobiol.2017.01.006
    Cryopreservation is the only existing method of storage of human adipose-derived stem cells (ASCs) for clinical use. However, cryopreservation has been shown to be detrimental to ASCs, particularly in term of cell viability. To restore the viability of cryopreserved ASCs, it is proposed to culture the cells in a hypoxic condition. To this end, we aim to investigate the effect of hypoxia on the cryopreserved human ASCs in terms of not only cell viability, but also their growth and stemness properties, which have not been explored yet. In this study, human ASCs were cultured under four different conditions: fresh (non-cryopreserved) cells cultured in 1) normoxia (21% O2) and 2) hypoxia (2% O2) and cryopreserved cells cultured in 3) normoxia and 4) hypoxia. ASCs at passage 3 were subjected to assessment of viability, proliferation, differentiation, and expression of stemness markers and hypoxia-inducible factor-1 alpha (HIF-1α). We found that hypoxia enhances the viability and the proliferation rate of cryopreserved ASCs. Further, hypoxia upregulates HIF-1α in cryopreserved ASCs, which in turn activates chondrogenic genes to promote chondrogenic differentiation. In conclusion, hypoxic-preconditioned cryopreserved ASCs could be an ideal cell source for cartilage repair and regeneration.
    Matched MeSH terms: Stem Cells/cytology; Adult Stem Cells/cytology*
  19. Chien WY, Huang HM, Kang YN, Chen KH, Chen C
    J Plast Reconstr Aesthet Surg, 2024 Jan;88:182-192.
    PMID: 37983981 DOI: 10.1016/j.bjps.2023.10.060
    BACKGROUND: Alopecia is a common and distressing medical condition that has been related to psychiatric disorders. Stem cell-derived conditioned medium (CM), a novel therapy for hair regeneration, has shown effectiveness in several trials.

    METHODS: This meta-analysis aims to explore the effectiveness of stem cell-derived CM in improving hair growth for patients of alopecia. We prospectively registered this systematic review and meta-analysis in PROSPERO (CRD42023410249). Clinical trials that the enrolled participants suffering from alopecia applied stem cell-derived CM were included. We calculated the mean and standard deviation for the hair density and thickness.

    RESULTS: Ten clinical trials were included in our analysis. On the basis of eight clinical trials (n = 221), our pooled results indicate that stem cell-derived CM is effective in increasing hair density (mean difference [MD]: 14.93, confidence interval [95% CI]: 10.20-19.67, p Stem cell-derived conditioned medium can effectively increase hair density and thickness for alopecia, and there is no difference between each method (topical application, microneedling, or injection).

    Matched MeSH terms: Stem Cells
  20. Gilbert-Jaramillo J, Komarasamy TV, Balasubramaniam VR, Heather LC, James WS
    Antiviral Res, 2024 Aug;228:105933.
    PMID: 38851593 DOI: 10.1016/j.antiviral.2024.105933
    The underlying threat of new Zika virus (ZIKV) outbreaks remains, as no vaccines or therapies have yet been developed. In vitro research has shown that glycolysis is a key factor to enable sustained ZIKV replication in neuroprogenitors. However, neither in vivo nor clinical investigation of glycolytic modulators as potential therapeutics for ZIKV-related fetal abnormalities has been conducted. Accordingly, we tested the therapeutic potential of metabolic modulators in relevant in vitro systems comprising two pools of neuroprogenitors (NPCs), which resemble early and late stages of pregnancy. Effective doses of metabolic modulators [3.0 μM] dimethyl fumarate (DMF), [3.2 mM] dichloroacetate (DCA), and [6.3 μM] VER-246608 were determined for these cells by their effect on lactate release, pyruvate dehydrogenase (PDH) activity and cell survival. The drugs were used in a 24h pre-treatment and kept throughout ZIKV infection of NPCs. Drug effects and ZIKV replication were assessed at 24- and 56-h post-infection. In early NPCs treated with DMF, DCA and VER-246608, there was a significant reduction in the extracellular release of ZIKV potentially by PDH-mediated increased mitochondrial oxidation of glucose. Out of the three drugs, only DCA was observed to reduce viral replication in late NPCs treated with DCA. Altogether, our findings suggest that reduction of anaerobic glycolysis could be of therapeutic potential against ZIKV-related fetal abnormalities and that clinical translation should consider the use of specific glycolytic modulators over different trimesters.
    Matched MeSH terms: Neural Stem Cells/drug effects; Neural Stem Cells/metabolism; Neural Stem Cells/virology
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