Displaying publications 1 - 20 of 31 in total

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  1. Chromosomal Analysis in Lineage-Specific Mouse Hematopoietic Stem Cells and Progenitors
    Yusoff NA, Abd Hamid Z, Chow PW, Shuib S, Taib IS, Budin SB
    Methods Mol Biol, 2024;2736:65-76.
    PMID: 36749486 DOI: 10.1007/7651_2022_477
    Hematopoiesis is maintained throughout life from the hematopoietic stem cell niche in which hematopoietic stem cells and lineage-specific hematopoietic progenitors (HSPCs) reside and regulate hematopoiesis. Meanwhile, HSPCs behavior is modulated by both cell intrinsic (e.g., transcriptional factors) and cell extrinsic (e.g., cytokines) factors. Dysregulation of these factors can alter HSPCs function, leading to disrupted hematopoiesis, cellular changes, and subsequent hematological diseases and malignancies. Moreover, it has been reported that chromosomal aberration (CA) in HSPCs following exposure to carcinogenic or genotoxic agents can initiate leukemia stem cells (LSCs) formation which lays a fundamental mechanism in leukemogenesis. Despite reported studies concerning the chromosomal integrity in HSPCs, CA analysis in lineage-specific HSPCs remains scarce. This indicates a need for a laboratory technique that allows the study of CA in specific HSPCs subpopulations comprising differential hematopoietic lineages. Thus, this chapter focuses on the structural (clastogenicity) and numerical (aneugenicity) form of CA analysis in lineage-specific HSPCs comprised of myeloid, erythroid and lymphoid lineages.In this protocol, we describe how to perform CA analysis in lineage-specific HSPCs derived from freshly isolated mouse bone marrow cells (MBMCs) using the combined techniques of colony-forming unit (CFU) and karyotyping. Prior to CA analysis, lineage-specific HSPCs for myeloid, erythroid, and lymphoid were enriched through colony-forming unit (CFU) assay. CFU assay assesses the proliferative ability and differentiation potential of an individual HSPC within a sample. About 6 to 14 days of cultures are required depending on the type of HSPCs lineage. The optimal duration is crucial to achieve sufficient colony growth that is needed for accurate CFU analysis via morphological identification and colony counting. Then, the CA focusing on clastogenicity and aneugenicity anomalies in respective HSPCs lineage for myeloid, erythroid and Pre-B lymphoid were investigated. The resulted karyotypes were classified according to the types of CA known as Robertsonian (Rb) translocation, hyperploidy or complex. We believe our protocol offers a significant contribution to be utilized as a reference method for chromosomal analysis in lineage-specific HSPCs subpopulations.
    Matched MeSH terms: Hematopoietic Stem Cells*
  2. Fulltext Molecular landscape of immune pressure and escape in aplastic anemia
    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
  3. The potential role of mesenchymal stem cells in modulating antiageing process
    Govindasamy V, Rajendran A, Lee ZX, Ooi GC, Then KY, Then KL, et al.
    Cell Biol Int, 2021 Oct;45(10):1999-2016.
    PMID: 34245637 DOI: 10.1002/cbin.11652
    Ageing and age-related diseases share some basic origin that largely converges on inflammation. Precisely, it boils down to a common pathway characterised by the appearance of a fair amount of proinflammatory cytokines known as inflammageing. Among the proposed treatment for antiageing, MSCs gained attention in recent years. Since mesenchymal stem cells (MSCs) can differentiate itself into a myriad of terminal cells, previously it was believed that these cells migrate to the site of injury and perform their therapeutic effect. However, with the more recent discovery of huge amounts of paracrine factors secreted by MSCs, it is now widely accepted that these cells do not engraft upon transplantation but rather unveil their benefits through excretion of bioactive molecules namely those involved in inflammatory and immunomodulatory activities. Conversely, the true function of these paracrine changes has not been thoroughly investigated all these years. Hence, this review will describe in detail on ways MSCs may capitalize its paracrine properties in modulating antiageing process. Through a comprehensive literature search various elements in the antiageing process, we aim to provide a novel treatment perspective of MSCs in antiageing related clinical conditions.
    Matched MeSH terms: Hematopoietic Stem Cells/cytology*
  4. Linking Benzene, in Utero Carcinogenicity and Fetal Hematopoietic Stem Cell Niches: A Mechanistic Review
    Yusoff NA, Abd Hamid Z, Budin SB, Taib IS
    Int J Mol Sci, 2023 Mar 28;24(7).
    PMID: 37047305 DOI: 10.3390/ijms24076335
    Previous research reported that prolonged benzene exposure during in utero fetal development causes greater fetal abnormalities than in adult-stage exposure. This phenomenon increases the risk for disease development at the fetal stage, particularly carcinogenesis, which is mainly associated with hematological malignancies. Benzene has been reported to potentially act via multiple modes of action that target the hematopoietic stem cell (HSCs) niche, a complex microenvironment in which HSCs and multilineage hematopoietic stem and progenitor cells (HSPCs) reside. Oxidative stress, chromosomal aberration and epigenetic modification are among the known mechanisms mediating benzene-induced genetic and epigenetic modification in fetal stem cells leading to in utero carcinogenesis. Hence, it is crucial to monitor exposure to carcinogenic benzene via environmental, occupational or lifestyle factors among pregnant women. Benzene is a well-known cause of adult leukemia. However, proof of benzene involvement with childhood leukemia remains scarce despite previously reported research linking incidences of hematological disorders and maternal benzene exposure. Furthermore, accumulating evidence has shown that maternal benzene exposure is able to alter the developmental and functional properties of HSPCs, leading to hematological disorders in fetus and children. Since HSPCs are parental blood cells that regulate hematopoiesis during the fetal and adult stages, benzene exposure that targets HSPCs may induce damage to the population and trigger the development of hematological diseases. Therefore, the mechanism of in utero carcinogenicity by benzene in targeting fetal HSPCs is the primary focus of this review.
    Matched MeSH terms: Hematopoietic Stem Cells/pathology
  5. 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/cytology*; Hematopoietic Stem Cells/metabolism; Hematopoietic Stem Cells/physiology*
  6. Fulltext Carica papaya induces in vitro thrombopoietic cytokines secretion by mesenchymal stem cells and haematopoietic cells
    Aziz J, Abu Kassim NL, Abu Kasim NH, Haque N, Rahman MT
    BMC Complement Altern Med, 2015;15:215.
    PMID: 26152209 DOI: 10.1186/s12906-015-0749-6
    Use of Carica papaya leaf extracts, reported to improve thrombocyte counts in dengue patients, demands further analysis on the underlying mechanism of its thrombopoietic cytokines induction
    Matched MeSH terms: Hematopoietic Stem Cells/drug effects*; Hematopoietic Stem Cells/metabolism
  7. Lineage-related cytotoxicity and clonogenic profile of 1,4-benzoquinone-exposed hematopoietic stem and progenitor cells
    Chow PW, Abdul Hamid Z, Chan KM, Inayat-Hussain SH, Rajab NF
    Toxicol Appl Pharmacol, 2015 Apr 1;284(1):8-15.
    PMID: 25645895 DOI: 10.1016/j.taap.2015.01.016
    Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) are sensitive targets for benzene-induced hematotoxicity and leukemogenesis. The impact of benzene exposure on the complex microenvironment of HSCs and HPCs remains elusive. This study aims to investigate the mechanism linking benzene exposure to targeting HSCs and HPCs using phenotypic and clonogenic analyses. Mouse bone marrow (BM) cells were exposed ex vivo to the benzene metabolite, 1,4-benzoquinone (1,4-BQ), for 24h. Expression of cellular surface antigens for HSC (Sca-1), myeloid (Gr-1, CD11b), and lymphoid (CD45, CD3e) populations were confirmed by flow cytometry. The clonogenicity of cells was studied using the colony-forming unit (CFU) assay for multilineage (CFU-GM and CFU-GEMM) and single-lineage (CFU-E, BFU-E, CFU-G, and CFU-M) progenitors. 1,4-BQ demonstrated concentration-dependent cytotoxicity in mouse BM cells. The percentage of apoptotic cells increased (p < 0.05) following 1,4-BQ exposure. Exposure to 1,4-BQ showed no significant effect on CD3e(+) cells but reduced the total counts of Sca-1(+), CD11b(+), Gr-1(+), and CD45(+) cells at 7 and 12 μM (p < 0.05). Furthermore, the CFU assay showed reduced (p < 0.05) clonogenicity in 1,4-BQ-treated cells. 1,4-BQ induced CFU-dependent cytotoxicity by significantly inhibiting colony growth for CFU-E, BFU-E, CFU-G, and CFU-M starting at a low concentration of exposure (5μM); whereas for the CFU-GM and CFU-GEMM, the inhibition of colony growth was remarkable only at 7 and 12μM of 1,4-BQ, respectively. Taken together, 1,4-BQ caused lineage-related cytotoxicity in mouse HPCs, demonstrating greater toxicity in single-lineage progenitors than in those of multi-lineage.
    Matched MeSH terms: Hematopoietic Stem Cells/drug effects*; Hematopoietic Stem Cells/metabolism; Hematopoietic Stem Cells/pathology
  8. Fulltext Cytogenetics and molecular genetic tests for the diagnosis and treatment of chronic myeloid leukemia
    Mohd Khairi Zahry, Ankathil, Ravindran
    Buletin Persatuan Genetik Malaysia, 2008;14(1):9-11.
    MyJurnal
    Chronic Myeloid Leukemia (CML) is a clonal disorder thought to originate in a single abnormal haematopoietic stem cell. This myeloproliferative fatal stem cell disorder comprises
    approximately 14% of all leukemias. In most cases, CML runs a triphasic course, which includes an initial chronic phase that transforms eventually into a blastic phase resembling acute leukemia. In 60%- 80% of patients, an intermediate or accelerated phase precedes the terminal blastic phase. Accelerated phase and blastic phase sometimes are lumped together and considered to be
    advanced phase CML. The entire continuum from chronic phase to blastic phase lasts a median of 3 to 5 years . This time period can be broken down in to the chronic phase which if untreated,
    lasts for 2 to 5 years and finally the fatal blastic phase, which lasts from 3 to 6 months. A patient can present in any of these 3 stages.
    Matched MeSH terms: Hematopoietic Stem Cells
  9. Effects of gestational diabetes mellitus on the quality and quantity of blood hematopoietic stem cells: a case-control study
    Tusimin M, Ahmed SME, Wei Lee K, Siew Mooi C, Md Noor S, Nordin N
    Croat Med J, 2021 Dec 31;62(6):590-597.
    PMID: 34981691
    AIM: To evaluate the effects of gestational diabetes mellitus (GDM) on the quantity and quality of hematopoietic stem cells (HSC).

    METHODS: In this case-control study, HSC were isolated from umbilical cord blood (UCB) procured at delivery from 63 mothers with GDM and 67 healthy mothers. Total nucleated cells (TNC) and CD34+ cells were quantified using BD FACSCalibur flow cytometer. The quantity and quality of stem cells were determined.

    RESULTS: The GDM group had lower total cord blood volume and lower number of nucleated HSC compared with healthy mothers. Regarding stem cell quantity parameters, they had significantly lower UCB volume (P=0.041), TNC count (P=0.022), total viable NC count (P=0.014), and CD34+ percentage (P=0.014). Regarding the quality of stem cells, they had significantly lower viable TNC percentage (P=0.015). The predictors for total TNC count were longer labor duration (adjusted B coefficient [p]: 0.031 [0.046]), greater estimated blood loss (0.089 [0.005]), female neonates (12.322 [0.049]), and higher placenta weight (0.080 [0.033]). The predictors of total viable NC count were greater estimated blood loss (0.092 [0.003]), female neonates (13.16 [0.035]), and greater placenta weight (0.083 [0.026]).

    CONCLUSION: The GDM group had much lower quantity and quality of UCB stem cells. Our results should be taken into consideration when drawing cord blood for unrelated stem cell banking in an obstetric unit to ensure the obtaining of optimal cord blood samples and to avoid unnecessary expenses.

    Matched MeSH terms: Hematopoietic Stem Cells
  10. Fulltext The Role of N-Acetylcysteine Supplementation on the Oxidative Stress Levels, Genotoxicity and Lineage Commitment Potential of Ex Vivo Murine Haematopoietic Stem/Progenitor Cells
    Hamid ZA, Tan HY, Chow PW, Harto KAW, Chan CY, Mohamed J
    Sultan Qaboos Univ Med J, 2018 May;18(2):e130-e136.
    PMID: 30210840 DOI: 10.18295/squmj.2018.18.02.002
    Objectives: The ex vivo maintenance of haematopoietic stem/progenitor cells (HSPCs) is crucial to ensure a sufficient supply of functional cells for research or therapeutic applications. However, when exposed to reactive oxygen species (ROS) in a normoxic microenvironment, HSPCs exhibit genomic instability which may diminish their quantity and quality. This study aimed to investigate the role of N-acetylcysteine (NAC) supplementation on the oxidative stress levels, genotoxicity and lineage commitment potential of murine haematopoietic stem/progenitor cells (HSPCs).

    Methods: This study was carried out at the Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia, between June 2016 and July 2017. Bone marrow cells were isolated from nine mice and cultured in a growth medium. Various concentrations of NAC between 0.125-2 μM were added to the culture for 48 hours; these cells were then compared to non-supplemented cells harvested from the remaining three mice as the control group. A trypan blue exclusion test was performed to determine cell viability, while intracellular ROS levels and genotoxicity were determined by hydroethidine staining and comet assay, respectively. The lineage commitment potential of erythroid, myeloid and pre-B-lymphoid progenitor cells was evaluated via colony-forming cell assay.

    Results: NAC supplementation at 0.25, 0.5 and 2 μM significantly increased cell viability (P <0.050), while intracellular ROS levels significantly decreased at 0.25 and 0.5 μM (P <0.050). Moreover, DNA damage was significantly reduced at all NAC concentrations (P <0.050). Finally, the potential lineage commitment of the cells was not significantly affected by NAC supplementation (P >0.050).

    Conclusion: The findings of this study indicate that NAC supplementation may potentially overcome the therapeutic limitations of ex vivo-maintained HSPCs.

    Matched MeSH terms: Hematopoietic Stem Cells/cytology; Hematopoietic Stem Cells/drug effects*; Hematopoietic Stem Cells/metabolism
  11. Fulltext Characterization of mononucleated human peripheral blood cells
    Ab Kadir R, Zainal Ariffin SH, Megat Abdul Wahab R, Kermani S, Senafi S
    ScientificWorldJournal, 2012;2012:843843.
    PMID: 22666162 DOI: 10.1100/2012/843843
    Unspecialized cells that can renew themselves and give rise to multiple differentiated cell types are termed stem cells. The objective of this study was to characterize and investigate, through molecular and biochemical analyses, the stemness of cells derived from isolated mononucleated cells that originated from peripheral blood. The isolated mononucleated cells were separated according to their physical characteristics (adherent and suspension), after 4 to 7 days into a 14-day culturing period in complete medium. Our results revealed that adherent and suspension cells were positive for mesenchymal stem cell (MSC) and hematopoietic stem cell (HSC) markers, respectively. Differentiation of adherent cells into osteoblasts was associated with expression of the OPN gene and increasing ALP enzyme activity, while differentiation of suspension cells into osteoclasts was associated with expression of the TRAP gene and increasing TRAP enzyme activity. In conclusion, molecular and biochemical analyses showed that mononucleated cells consist of MSC (adherent) and HSC (suspension), and both cell types are able to differentiate into specialized cells from their respective lineage: osteoblast (MSC) and osteoclast (HSC).
    Matched MeSH terms: Hematopoietic Stem Cells/cytology
  12. The effect of human mesenchymal stem cells on tumour cell proliferation
    Sarmadi VH, Heng FS, Ramasamy R
    Med J Malaysia, 2008 Jul;63 Suppl A:63-4.
    PMID: 19024985
    The therapeutic effect of mesenchymal stem cells (MSC) has been extensively investigated in recent decades, however this therapeutic effect has not been fully characterised. The aim of this study is to elucidate the inhibitory effect of MSC on haematopoietic tumour cells proliferation such as BV173 cell line. To this end, MSC generated from bone marrow, after immunophenotyping, they were co-cultured with tumour cell. The result shows that MSC profoundly inhibit the tumour cell proliferation via arresting the tumour cells at G0 and G1 phase of cell cycle.
    Matched MeSH terms: Hematopoietic Stem Cells*
  13. Genetic, epigenetic, and lineage-directed mechanisms in benzene-induced malignancies and hematotoxicity targeting hematopoietic stem cells niche
    Dewi R, Hamid ZA, Rajab NF, Shuib S, Razak SA
    Hum Exp Toxicol, 2020 May;39(5):577-595.
    PMID: 31884827 DOI: 10.1177/0960327119895570
    Benzene is a known hematotoxic and leukemogenic agent with hematopoietic stem cells (HSCs) niche being the potential target. Occupational and environmental exposure to benzene has been linked to the incidences of hematological disorders and malignancies. Previous studies have shown that benzene may act via multiple modes of action targeting HSCs niche, which include induction of chromosomal and micro RNA aberrations, leading to genetic and epigenetic modification of stem cells and probable carcinogenesis. However, understanding the mechanism linking benzene to the HSCs niche dysregulation is challenging due to complexity of its microenvironment. The niche is known to comprise of cell populations accounted for HSCs and their committed progenitors of lymphoid, erythroid, and myeloid lineages. Thus, it is fundamental to address novel approaches via lineage-directed strategy to elucidate precise mechanism involved in benzene-induced toxicity targeting HSCs and progenitors of different lineages. Here, we review the key genetic and epigenetic factors that mediate hematotoxicological effects by benzene and its metabolites in targeting HSCs niche. Overall, the use of combined genetic, epigenetic, and lineage-directed strategies targeting the HSCs niche is fundamental to uncover the key mechanisms in benzene-induced hematological disorders and malignancies.
    Matched MeSH terms: Hematopoietic Stem Cells/drug effects*
  14. Fulltext Highly efficient Runx1 enhancer eR1-mediated genetic engineering for fetal, child and adult hematopoietic stem cells
    Koh CP, Bahirvani AG, Wang CQ, Yokomizo T, Ng CEL, Du L, et al.
    Gene, 2023 Jan 30;851:147049.
    PMID: 36384171 DOI: 10.1016/j.gene.2022.147049
    A cis-regulatory genetic element which targets gene expression to stem cells, termed stem cell enhancer, serves as a molecular handle for stem cell-specific genetic engineering. Here we show the generation and characterization of a tamoxifen-inducible CreERT2 transgenic (Tg) mouse employing previously identified hematopoietic stem cell (HSC) enhancer for Runx1, eR1 (+24 m). Kinetic analysis of labeled cells after tamoxifen injection and transplantation assays revealed that eR1-driven CreERT2 activity marks dormant adult HSCs which slowly but steadily contribute to unperturbed hematopoiesis. Fetal and child HSCs that are uniformly or intermediately active were also efficiently targeted. Notably, a gene ablation at distinct developmental stages, enabled by this system, resulted in different phenotypes. Similarly, an oncogenic Kras induction at distinct ages caused different spectrums of malignant diseases. These results demonstrate that the eR1-CreERT2 Tg mouse serves as a powerful resource for the analyses of both normal and malignant HSCs at all developmental stages.
    Matched MeSH terms: Hematopoietic Stem Cells*
  15. Fulltext The role of Hibiscus sabdariffa L. (Roselle) in maintenance of ex vivo murine bone marrow-derived hematopoietic stem cells
    Abdul Hamid Z, Lin Lin WH, Abdalla BJ, Bee Yuen O, Latif ES, Mohamed J, et al.
    ScientificWorldJournal, 2014;2014:258192.
    PMID: 25405216 DOI: 10.1155/2014/258192
    Hematopoietic stem cells- (HSCs-) based therapy requires ex vivo expansion of HSCs prior to therapeutic use. However, ex vivo culture was reported to promote excessive production of reactive oxygen species (ROS), exposing HSCs to oxidative damage. Efforts to overcome this limitation include the use of antioxidants. In this study, the role of Hibiscus sabdariffa L. (Roselle) in maintenance of cultured murine bone marrow-derived HSCs was investigated. Aqueous extract of Roselle was added at varying concentrations (0-1000 ng/mL) for 24 hours to the freshly isolated murine bone marrow cells (BMCs) cultures. Effects of Roselle on cell viability, reactive oxygen species (ROS) production, glutathione (GSH) level, superoxide dismutase (SOD) activity, and DNA damage were investigated. Roselle enhanced the survival (P < 0.05) of BMCs at 500 and 1000 ng/mL, increased survival of Sca-1(+) cells (HSCs) at 500 ng/mL, and maintained HSCs phenotype as shown from nonremarkable changes of surface marker antigen (Sca-1) expression in all experimental groups. Roselle increased (P < 0.05) the GSH level and SOD activity but the level of reactive oxygen species (ROS) was unaffected. Moreover, Roselle showed significant cellular genoprotective potency against H2O2-induced DNA damage. Conclusively, Roselle shows novel property as potential supplement and genoprotectant against oxidative damage to cultured HSCs.
    Matched MeSH terms: Hematopoietic Stem Cells/drug effects*; Hematopoietic Stem Cells/physiology*
  16. Fulltext Differentiation of dental pulp stem cells into neuron-like cells in serum-free medium
    Zainal Ariffin SH, Kermani S, Zainol Abidin IZ, Megat Abdul Wahab R, Yamamoto Z, Senafi S, et al.
    Stem Cells Int, 2013;2013:250740.
    PMID: 24348580 DOI: 10.1155/2013/250740
    Dental pulp tissue contains dental pulp stem cells (DPSCs). Dental pulp cells (also known as dental pulp-derived mesenchymal stem cells) are capable of differentiating into multilineage cells including neuron-like cells. The aim of this study was to examine the capability of DPSCs to differentiate into neuron-like cells without using any reagents or growth factors. DPSCs were isolated from teeth extracted from 6- to 8-week-old mice and maintained in complete medium. The cells from the fourth passage were induced to differentiate by culturing in medium without serum or growth factors. RT-PCR molecular analysis showed characteristics of Cd146(+) , Cd166(+) , and Cd31(-) in DPSCs, indicating that these cells are mesenchymal stem cells rather than hematopoietic stem cells. After 5 days of neuronal differentiation, the cells showed neuron-like morphological changes and expressed MAP2 protein. The activation of Nestin was observed at low level prior to differentiation and increased after 5 days of culture in differentiation medium, whereas Tub3 was activated only after 5 days of neuronal differentiation. The proliferation of the differentiated cells decreased in comparison to that of the control cells. Dental pulp stem cells are induced to differentiate into neuron-like cells when cultured in serum- and growth factor-free medium.
    Matched MeSH terms: Hematopoietic Stem Cells
  17. The RUNX complex: reaching beyond haematopoiesis into immunity
    Voon DC, Hor YT, Ito Y
    Immunology, 2015 Dec;146(4):523-36.
    PMID: 26399680 DOI: 10.1111/imm.12535
    Among their diverse roles as transcriptional regulators during development and cell fate specification, the RUNX transcription factors are best known for the parts they play in haematopoiesis. RUNX proteins are expressed throughout all haematopoietic lineages, being necessary for the emergence of the first haematopoietic stem cells to their terminal differentiation. Although much progress has been made since their discoveries almost two decades ago, current appreciation of RUNX in haematopoiesis is largely grounded in their lineage-specifying roles. In contrast, the importance of RUNX to immunity has been mostly obscured for historic, technical and conceptual reasons. However, this paradigm is likely to shift over time, as a primary purpose of haematopoiesis is to resource the immune system. Furthermore, recent evidence suggests a role for RUNX in the innate immunity of non-haematopoietic cells. This review takes a haematopoiesis-centric approach to collate what is known of RUNX's contribution to the overall mammalian immune system and discuss their growing prominence in areas such as autoimmunity, inflammatory diseases and mucosal immunity.
    Matched MeSH terms: Hematopoietic Stem Cells
  18. Fulltext Misfolded N-CoR is Linked to the Ectopic Reactivation of CD34/Flt3-Based Stem-Cell Phenotype in Promyelocytic and Monocytic Acute Myeloid Leukemia
    Nin DS, Li F, Visvanathan S, Khan M
    Front Oncol, 2015;5:210.
    PMID: 26500885 DOI: 10.3389/fonc.2015.00210
    Nuclear receptor co-repressor (N-CoR) is the key component of generic co-repressor complex essential for the transcriptional control of genes involved in cellular hemostasis. We have recently reported that N-CoR actively represses Flt3, a key factor of hematopoietic stem cells (HSC) self-renewal and growth, and that de-repression of Flt3 by the misfolded N-CoR plays an important role in the pathogenesis of promyelocytic and monocytic acute myeloid leukemia (AML). The leukemic cells derived from the promyelocytic and monocytic AML are distinctly characterized by the ectopic reactivation of stem cell phenotypes in relatively committed myeloid compartment. However, the molecular mechanism underlying this phenomenon is not known. Here, we report that N-CoR function is essential for the commitment of primitive hematopoietic cells to the cells of myeloid lineage and that loss of N-CoR function due to misfolding is linked to the ectopic reactivation of generic stem cell phenotypes in promyelocytic and monocytic AML. Analysis of N-CoR and Flt3 transcripts in mouse hematopoietic cells revealed a positive correlation between N-CoR level and the commitment of myeloid cells and an inverse correlation between N-CoR and Flt3 levels in primitive as well as committed myeloid cells. Enforced N-CoR expression in mouse HSCs inhibited their growth and self-renewal potentials and promoted maturation toward cells of myeloid lineage, suggesting a role of N-CoR in the commitment of cells of myeloid lineage. In contrast to AML cells with natively folded N-CoR, primary and secondary promyelocytic and monocytic AML cells harboring the misfolded N-CoR were highly positive for Flt3 and myeloid antigen-based HSC marker CD34. Genetic and therapeutic restoration of N-CoR conformation significantly down-regulated the CD34 levels in monocytic AML cells, suggesting an important role of N-CoR in the suppression of CD34-based HSC phenotypes. These findings collectively suggest that N-CoR is crucial for the commitment of primitive hematopoietic cells to cells of myeloid lineage and that misfolded N-CoR may contribute to transformation of committed myeloid cells through the ectopic reactivation of Flt3/CD34-based stem cell phenotypes in promyelocytic and monocytic AML. Moreover, these findings provide novel mechanistic insights into the formation of leukemic stem cells in subsets of AML and identify the misfolded N-CoR as a subtype-specific biomarker of AML.
    Matched MeSH terms: Hematopoietic Stem Cells
  19. Lineage-related and particle size-dependent cytotoxicity of chitosan nanoparticles on mouse bone marrow-derived hematopoietic stem and progenitor cells
    Omar Zaki SS, Katas H, Hamid ZA
    Food Chem Toxicol, 2015 Nov;85:31-44.
    PMID: 26051352 DOI: 10.1016/j.fct.2015.05.017
    Chitosan nanoparticles (CSNPs) have potential applications in stem cell research. In this study, ex vivo cytotoxicity of CSNPs on mouse bone marrow-derived (MBMCs) hematopoietic stem and progenitor cells (HSPCs) was determined. MBMCs were exposed to CSNPs of different particle sizes at various concentrations for up to 72 h. Cytotoxicity effect of CSNPs on MBMCs was determined using MTT, Live/Dead Viability/Cytotoxicity assays and flow cytometry analysis of surface antigens on HSCs (Sca-1(+)), myeloid-committed progenitors (CD11b(+), Gr-1(+)), and lymphoid-committed progenitors (CD45(+), CD3e(+)). At 24 h incubation, MBMCs' viability was not affected by CSNPs. At 48 and 72 h, significant reduction was detected at higher CSNPs concentrations. Small CSNPs (200 nm) significantly reduced MBMCs' viability while medium-sized particle (∼400 nm) selectively promoted MBMCs growth. Surface antigen assessment demonstrated lineage-dependent effect. Significant decrease in Sca-1(+) cells percentage was observed for medium-sized particle at the lowest CSNPs concentration. Meanwhile, reduction of CD11b(+) and Gr-1(+) cells percentage was detected at high and intermediate concentrations of medium-sized and large CSNPs. Percentage of CD45(+) and CD3e(+) cells along with ROS levels were not significantly affected by CSNPs. In conclusion, medium-sized and large CSNPs were relatively non-toxic at lower concentrations. However, further investigations are necessary for therapeutic applications.
    Matched MeSH terms: Hematopoietic Stem Cells
  20. HLA-B*38:64, an HLA-B*38 variant, detected in a Singaporean Malay unrelated hematopoietic stem cell donor
    Cho L, Kaur A, Cereb N, Lin PY, Yang KL
    HLA, 2020 08;96(2):217-218.
    PMID: 32227685 DOI: 10.1111/tan.13873
    One nucleotide substitution in codon 89 of HLA-B*38:02:01:01 results in a novel allele, HLA-B*38:64.
    Matched MeSH terms: Hematopoietic Stem Cells
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