Displaying publications 161 - 180 of 3311 in total

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  1. 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: Cells, Cultured; Insulin-Secreting Cells/cytology; Insulin-Secreting Cells/drug effects; Insulin-Secreting Cells/metabolism; Insulin-Secreting Cells/transplantation*; Induced Pluripotent Stem Cells/cytology*
  2. Boo L, Ho WY, Mohd Ali N, Yeap SK, Ky H, Chan KG, et al.
    PeerJ, 2017;5:e3551.
    PMID: 28717596 DOI: 10.7717/peerj.3551
    Breast cancer spheroids have been widely used as in vitro models of cancer stem cells (CSCs), yet little is known about their phenotypic characteristics and microRNAs (miRNAs) expression profiles. The objectives of this research were to evaluate the phenotypic characteristics of MDA-MB-231 spheroid-enriched cells for their CSCs properties and also to determine their miRNAs expression profile. Similar to our previously published MCF-7 spheroid, MDA-MB-231 spheroid also showed typical CSCs characteristics namely self-renewability, expression of putative CSCs-related surface markers and enhancement of drug resistance. From the miRNA profile, miR-15b, miR-34a, miR-148a, miR-628 and miR-196b were shown to be involved in CSCs-associated signalling pathways in both models of spheroids, which highlights the involvement of these miRNAs in maintaining the CSCs features. In addition, unique clusters of miRNAs namely miR-205, miR-181a and miR-204 were found in basal-like spheroid whereas miR-125, miR-760, miR-30c and miR-136 were identified in luminal-like spheroid. Our results highlight the roles of miRNAs as well as novel perspectives of the relevant pathways underlying spheroid-enriched CSCs in breast cancer.
    Matched MeSH terms: Neoplastic Stem Cells; MCF-7 Cells
  3. Sinon S, Rich A, Firth N, Seymour G
    Sains Malaysiana, 2013;42:65-71.
    Cell mediated immunity is currently thought to be involved in the pathogenesis of oral mucosal lichen planus (OMLP). However, literature reveals there is no large scale data of immunohistochemistry (IHC) study on these immune cell populations. The aim of this study was to assess and compare immune cell surface identification markers CD3, CD4, CD8, CD19 and CD83 between the OMLP (n=40) and non-specific inflammatory lesions (as control group) (n=10) qualitatively and quantitatively. Kruskal-Wallis and Mann Whitney U tests have been used to make comparison between the test and control group, p values of less than 0.05 was considered to be statistically significant. T cell surface markers (CD3+, CD4+ and CD8+), B cells (CD19+) and mature dendritic cells (CD83+) showed intense immunostaining in OMLP tissues with a significantly higher expression of positive cells than in the control group (p<0.05). CD3, CD4 and CD8+ve T cells were the predominant inflammatory cell type in OMLP rather than CD19+ B cells, supporting the role of Th1 cells in the pathogenesis of OMLP. CD83+ mature dendritic cells were present in the least number and were mostly localized to areas where there were aggregates of lymphocyte. There was a positive correlation and direct relationship between T and B lymphocyte subsets whereby as one subset increased, the other follows.
    Matched MeSH terms: Dendritic Cells; Th1 Cells
  4. Teo GY, Rasedee A, Al-Haj NA, Beh CY, How CW, Rahman HS, et al.
    Saudi J Biol Sci, 2020 Feb;27(2):653-658.
    PMID: 32210684 DOI: 10.1016/j.sjbs.2019.11.032
    Erythropoietin receptors (EPORs) are present not only in erythrocyte precursors but also in non-hematopoietic cells including cancer cells. In this study, we determined the effect of fetal bovine serum (FBS) in culture medium on the EPOR expression and viability of the estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells. Using flow cytometry, we showed that the inclusion of 10% FBS in the medium increased the EPOR expressions and viabilities of MDA-MB-231 and MCF-7 cells. The MDA-MB-231 showed greater EPOR expression than MCF-7 cells, suggesting that the presence of ERs on cells is associated with poor expression of EPOR. Culture medium containing 10% FBS also caused increased number of breast cancer cells entering the synthesis phase of the cell cycle. The study also showed that rHuEPO treatment did not affect viability of breast cancer cells. In conclusion, it was shown that the inclusion of FBS in culture medium increased expression of EPOR in breast cancer cells and rHuEPO treatment had no effect on the proliferation of these cancer cells.
    Matched MeSH terms: Erythroid Precursor Cells; MCF-7 Cells
  5. Lee SH, Looi CY, Chong PP, Foo JB, Looi QH, Ng CX, et al.
    Curr Stem Cell Res Ther, 2021;16(5):551-562.
    PMID: 32988356 DOI: 10.2174/1574888X15666200928110923
    Mesenchymal Stem Cells (MSCs) are adult stem cells that are gaining worldwide attention for their multi-potential use in tissue engineering-based regenerative medicine. They can be obtained from numerous sources and one of the excellent sources is the dental tissue, such as Stem cells that are extracted from the Human Exfoliated Deciduous teeth (SHED). SHED are considered ideal due to their inherent characteristics, including the capability to proliferate quickly with minimal oncogenesis risk, multipotency capacity and their ability to suppress the immune system. On top of these positive cell traits, SHED are easily accessible with the patient's safety assured, posing less ethical issues and could also provide a sufficient number of cells for prospective clinical uses. This is primarily attributed to their ability to differentiate into multiple cell linages, including osteoblasts, odontoblasts, neuronal cells, adipocytes, as well as endothelial cells. Albeit SHED having a bright future, there still remains an obstacle to develop reliable experimental techniques to retain the long-term regeneration potential of the stem cells for prospective research and clinical applications. Therefore, this review aims to describe the various isolation, expansion and cryopreservation techniques used by researchers in this stem cell field. Optimization of these techniques is crucial to obtain distinct SHED culture with preserved stem cell properties, which enable more reproducible results that will be the key for further stem cell therapy development.
    Matched MeSH terms: Stem Cells/cytology*
  6. Ng CY, Chai JY, Foo JB, Mohamad Yahaya NH, Yang Y, Ng MH, et al.
    Int J Nanomedicine, 2021;16:6749-6781.
    PMID: 34621125 DOI: 10.2147/IJN.S327059
    Treatment of cartilage defects such as osteoarthritis (OA) and osteochondral defect (OCD) remains a huge clinical challenge in orthopedics. OA is one of the most common chronic health conditions and is mainly characterized by the degeneration of articular cartilage, shown in the limited capacity for intrinsic repair. OCD refers to the focal defects affecting cartilage and the underlying bone. The current OA and OCD management modalities focus on symptom control and on improving joint functionality and the patient's quality of life. Cell-based therapy has been evaluated for managing OA and OCD, and its chondroprotective efficacy is recognized mainly through paracrine action. Hence, there is growing interest in exploiting extracellular vesicles to induce cartilage regeneration. In this review, we explore the in vivo evidence of exosomes on cartilage regeneration. A total of 29 in vivo studies from the PubMed and Scopus databases were identified and analyzed. The studies reported promising results in terms of in vivo exosome delivery and uptake; improved cartilage morphological, histological, and biochemical outcomes; enhanced subchondral bone regeneration; and improved pain behavior following exosome treatment. In addition, exosome therapy is safe, as the included studies documented no significant complications. Modifying exosomal cargos further increased the cartilage and subchondral bone regeneration capacity of exosomes. We conclude that exosome administration is a potent cell-free therapy for alleviating OA and OCD. However, additional studies are needed to confirm the therapeutic potential of exosomes and to identify the standard protocol for exosome-based therapy in OA and OCD management.
    Matched MeSH terms: Mesenchymal Stromal Cells*
  7. Looi SY, Bastion MC, Leow SN, Luu CD, Hairul NMH, Ruhaslizan R, et al.
    Indian J Ophthalmol, 2022 Jan;70(1):201-209.
    PMID: 34937239 DOI: 10.4103/ijo.IJO_473_21
    Purpose: There are no effective treatments currently available for optic nerve transection injuries. Stem cell therapy represents a feasible future treatment option. This study investigated the therapeutic potential of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation in rats with optic nerve injury.

    Methods: Sprague-Dawley (SD) rats were divided into three groups: a no-treatment control group (n = 6), balanced salt solution (BSS) treatment group (n = 6), and hUC-MSCs treatment group (n = 6). Visual functions were assessed by flash visual evoked potential (fVEP) at baseline, Week 3, and Week 6 after optic nerve crush injury. Right eyes were enucleated after 6 weeks for histology.

    Results: The fVEP showed shortened latency delay and increased amplitude in the hUC-MSCs treated group compared with control and BSS groups. Higher cellular density was detected in the hUC-MSC treated group compared with the BSS and control groups. Co-localized expression of STEM 121 and anti-S100B antibody was observed in areas of higher nuclear density, both in the central and peripheral regions.

    Conclusion: Peribulbar transplantation of hUC-MSCs demonstrated cellular integration that can potentially preserve the optic nerve function with a significant shorter latency delay in fVEP and higher nuclear density on histology, and immunohistochemical studies observed cell migration particularly to the peripheral regions of the optic nerve.

    Matched MeSH terms: Mesenchymal Stromal Cells*
  8. Edwards MJ, Wilson GC, Keitsch S, Soddemann M, Wilker B, Müller CP, et al.
    J Neurochem, 2022 Nov;163(4):357-369.
    PMID: 36227646 DOI: 10.1111/jnc.15708
    Major depressive disorder (MDD) is a severe disease of unknown pathogenesis with a lifetime prevalence of ~10%. Therapy requires prolonged treatment that often fails. We have previously demonstrated that ceramide levels in the blood plasma of patients and in mice with experimental MDD are increased. Neutralization of blood plasma ceramide prevented experimental MDD in mice. Mechanistically, we demonstrated that blood plasma ceramide accumulated in endothelial cells of the hippocampus, inhibited phospholipase D (PLD) and thereby decreased phosphatidic acid in the hippocampus. Here, we demonstrate that phosphatidic acid binds to and controls the activity of phosphotyrosine phosphatase (PTP1B) in the hippocampus and thus determines tyrosine phosphorylation of a variety of cellular proteins including TrkB. Injection of PLD, phosphatidic acid, or inhibition of PTP1B abrogated MDD and normalized cellular tyrosine phosphorylation, including phosphorylation of TrkB and neurogenesis in the hippocampus. Most importantly, these treatments also rapidly normalized behavior of mice with experimental MDD. Since phosphatidic acid binds to and inhibits PTP1B, the lack of phosphatidic acid results in increased activity of PTP1B and thereby in reduced tyrosine phosphorylation of TrkB and other cellular proteins. Thus, our data indicate a novel pathogenetic mechanism of and a rapidly acting targeted treatment for MDD.
    Matched MeSH terms: Endothelial Cells/metabolism
  9. Siti Sarah CO, Nur Husna SM, Md Shukri N, Wong KK, Mohd Ashari NS
    PeerJ, 2022;10:e13314.
    PMID: 35480562 DOI: 10.7717/peerj.13314
    Allergic rhinitis (AR) is a common allergic disease characterized by disruption of nasal epithelial barrier. In this study, we investigated the mRNA expression of zonula occludens-1 (ZO-1), ZO-2 and ZO-3 and histone deacetylase 1 (HDAC1) and HDAC2 in AR patients compared to healthy controls. RNA samples were extracted from nasal epithelial cells of house dust mites (HDMs)-sensitized AR patients and healthy controls (n = 28 in each group). The RNAs were reverse transcribed into cDNAs for measurement of ZO-1, ZO-2, ZO-3, HDAC1 and HDAC2 expression levels by quantitative PCR. The mRNA expression of ZO-1 was significantly decreased in AR patients compared to healthy controls (p = 0.010). No significant difference was observed in the expression levels of ZO-2, ZO-3, HDAC1 and HDAC2 in AR patients compared to healthy controls. We found significant associations of higher HDAC2 levels in AR patients with lower frequency of changing bedsheet (p = 0.043) and with AR patients sensitized to Dermatophagoides farinae (p = 0.041). Higher expression of ZO-2 was observed in AR patients who had pets (p = 0.007). In conclusion, our data indicated that ZO-1 expression was lower in AR patients contributing to decreased integrity of nasal epithelial barrier integrity, and HDAC2 may be involved in the pathogenesis of the disease.
    Matched MeSH terms: Epithelial Cells/metabolism
  10. Cheong HC, Cheok YY, Chan YT, Tang TF, Sulaiman S, Looi CY, et al.
    BMC Microbiol, 2023 Mar 04;23(1):58.
    PMID: 36870960 DOI: 10.1186/s12866-023-02802-3
    BACKGROUND: Genital Chlamydia trachomatis infection is the most common bacterial sexual transmitted disease that causes severe complications including pelvic inflammatory disease, ectopic pregnancy, and infertility in females. The Pgp3 protein encoded by C. trachomatis plasmid has been speculated to be an important player in chlamydial pathogenesis. However, the precise function of this protein is unknown and thus remains to be thoroughly investigated.

    METHODS: In this study, we synthesized Pgp3 protein for in vitro stimulation in the Hela cervical carcinoma cells.

    RESULTS AND CONCLUSION: We showed that Pgp3 induced prominent expression of host inflammatory cytokine genes including interleukin-6 (IL-6), IL-8, tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and chemokine C-X-C motif ligand 1 (CXCL1), implying a possible role of Pgp3 in modulating the inflammatory reaction in the host.

    Matched MeSH terms: Epithelial Cells; HeLa Cells
  11. Kou M, Huang L, Yang J, Chiang Z, Chen S, Liu J, et al.
    Cell Death Dis, 2022 Jul 04;13(7):580.
    PMID: 35787632 DOI: 10.1038/s41419-022-05034-x
    Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal and multipotent differentiation. There is compelling evidence that the therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental paracrine effectors of MSCs and play a crucial role in intercellular communication, existing in various body fluids and cell supernatants. Since MSC-derived EVs retain the function of protocells and have lower immunogenicity, they have a wide range of prospective therapeutic applications with advantages over cell therapy. We describe some characteristics of MSC-EVs, and discuss their role in immune regulation and regeneration, with emphasis on the molecular mechanism and application of MSC-EVs in the treatment of fibrosis and support tissue repair. We also highlight current challenges in the clinical application of MSC-EVs and potential ways to overcome the problem of quality heterogeneity.
    Matched MeSH terms: Mesenchymal Stromal Cells*
  12. Chin SP, Saffery NS, Then KY, Cheong SK
    In Vitro Cell Dev Biol Anim, 2024 Mar;60(3):307-319.
    PMID: 38421574 DOI: 10.1007/s11626-024-00852-z
    Human umbilical cord-mesenchymal stem cells (hUC-MSCs) have been widely investigated as a new therapeutic agent to treat injuries and inflammatory-mediated and autoimmune diseases. Previous studies have reported on the safety of low-dose infusion of hUC-MSCs, but information on the cell behaviour at higher doses and frequency of injection of the cells remains uncertain. The aim of the present study was to demonstrate the safety and efficacy of hUC-MSCs by Cytopeutics® (Selangor, Malaysia) from low to an extremely high dose in different monitoring periods in healthy BALB/c mice as well as assessing the tumorigenicity of the cells in B-NDG SCID immunocompromised mice. Umbilical cord from two healthy human newborns was obtained and the isolation of the hUC-MSCs was performed based on previous established method. Assessment of the cells at different doses of single or multiple administrations was performed on healthy BALB/c mice in dose range finding, sub-acute (7 d and 28 d) and sub-chronic periods (90 d). Tumorigenicity potential of Cytopeutics® hUC-MSCs was also evaluated on B-NDG immunocompromised mice for 26 wk. Single or multiple administrations of Cytopeutics® hUC-MSCs up to 40 × 106 cells per kilogramme of body weight (kg BW) were found to have no adverse effect in terms of clinical symptoms, haematology and other laboratory parameters, and histology examination in healthy BALB/c mice. hUC-MSCs were also found to reduce pro-inflammatory cytokines (IL-6 and TNF-α) in a dose-dependent manner. No sign of tumor formation was observed in B-NDG mice in the 26-wk tumorigenicity assessment. Single or multiple administration of allogenic Cytopeutics® hUC-MSCs was safe even at very high doses, is non-tumorigenic and did not cause adverse effects in mice throughout the evaluation periods. In addition, Cytopeutics® hUC-MSCs exhibited immunomodulatory effect in a dose-dependent manner.
    Matched MeSH terms: Mesenchymal Stromal Cells*
  13. Chan WT, Garcillán-Barcia MP, Yeo CC, Espinosa M
    FEMS Microbiol Rev, 2023 Sep 05;47(5).
    PMID: 37715317 DOI: 10.1093/femsre/fuad052
    Toxin-antitoxin (TA) systems are entities found in the prokaryotic genomes, with eight reported types. Type II, the best characterized, is comprised of two genes organized as an operon. Whereas toxins impair growth, the cognate antitoxin neutralizes its activity. TAs appeared to be involved in plasmid maintenance, persistence, virulence, and defence against bacteriophages. Most Type II toxins target the bacterial translational machinery. They seem to be antecessors of Higher Eukaryotes and Prokaryotes Nucleotide-binding (HEPN) RNases, minimal nucleotidyltransferase domains, or CRISPR-Cas systems. A total of four TAs encoded by Streptococcus pneumoniae, RelBE, YefMYoeB, Phd-Doc, and HicAB, belong to HEPN-RNases. The fifth is represented by PezAT/Epsilon-Zeta. PezT/Zeta toxins phosphorylate the peptidoglycan precursors, thereby blocking cell wall synthesis. We explore the body of knowledge (facts) and hypotheses procured for Type II TAs and analyse the data accumulated on the PezAT family. Bioinformatics analyses showed that homologues of PezT/Zeta toxin are abundantly distributed among 14 bacterial phyla mostly in Proteobacteria (48%), Firmicutes (27%), and Actinobacteria (18%), showing the widespread distribution of this TA. The pezAT locus was found to be mainly chromosomally encoded whereas its homologue, the tripartite omega-epsilon-zeta locus, was found mostly on plasmids. We found several orphan pezT/zeta toxins, unaccompanied by a cognate antitoxin.
    Matched MeSH terms: Prokaryotic Cells/metabolism
  14. Ooi SE, Sarpan N, Taranenko E, Feshah I, Nuraziyan A, Roowi SH, et al.
    Plant Mol Biol, 2023 Mar;111(4-5):345-363.
    PMID: 36609897 DOI: 10.1007/s11103-022-01330-4
    The mantled phenotype is an abnormal somaclonal variant arising from the oil palm cloning process and severe phenotypes lead to oil yield losses. Hypomethylation of the Karma retrotransposon within the B-type MADS-box EgDEF1 gene has been associated with this phenotype. While abnormal Karma-EgDEF1 hypomethylation was detected in mantled clones, we examined the methylation state of Karma in ortets that gave rise to high mantling rates in their clones. Small RNAs (sRNAs) were proposed to play a role in Karma hypomethylation as part of the RNA-directed DNA methylation process, hence differential expression analysis of sRNAs between the ortet groups was conducted. While no sRNA was differentially expressed at the Karma-EgDEF1 region, three sRNA clusters were differentially regulated in high-mantling ortets. The first two down-regulated clusters were possibly derived from long non-coding RNAs while the third up-regulated cluster was derived from the intron of a DnaJ chaperone gene. Several predicted mRNA targets for the first two sRNA clusters conversely displayed increased expression in high-mantling relative to low-mantling ortets. These predicted mRNA targets may be associated with defense or pathogenesis response. In addition, several differentially methylated regions (DMRs) were identified in Karma and its surrounding regions, mainly comprising subtle CHH hypomethylation in high-mantling ortets. Four of the 12 DMRs were located in a region corresponding to hypomethylated areas at the 3'end of Karma previously reported in mantled clones. Further investigations on these sRNAs and DMRs may indicate the predisposition of certain ortets towards mantled somaclonal variation.
    Matched MeSH terms: Clone Cells/metabolism
  15. Xiao Y, Sloan J, Hepworth C, Fradera-Soler M, Mathers A, Thorley R, et al.
    New Phytol, 2023 Jan;237(2):441-453.
    PMID: 36271620 DOI: 10.1111/nph.18564
    Leaf structure plays an important role in photosynthesis. However, the causal relationship and the quantitative importance of any single structural parameter to the overall photosynthetic performance of a leaf remains open to debate. In this paper, we report on a mechanistic model, eLeaf, which successfully captures rice leaf photosynthetic performance under varying environmental conditions of light and CO2 . We developed a 3D reaction-diffusion model for leaf photosynthesis parameterised using a range of imaging data and biochemical measurements from plants grown under ambient and elevated CO2 and then interrogated the model to quantify the importance of these elements. The model successfully captured leaf-level photosynthetic performance in rice. Photosynthetic metabolism underpinned the majority of the increased carbon assimilation rate observed under elevated CO2 levels, with a range of structural elements making positive and negative contributions. Mesophyll porosity could be varied without any major outcome on photosynthetic performance, providing a theoretical underpinning for experimental data. eLeaf allows quantitative analysis of the influence of morphological and biochemical properties on leaf photosynthesis. The analysis highlights a degree of leaf structural plasticity with respect to photosynthesis of significance in the context of attempts to improve crop photosynthesis.
    Matched MeSH terms: Mesophyll Cells/metabolism
  16. 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*
  17. 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*
  18. Hiew VV, Teoh PL
    Mol Biol Rep, 2024 Mar 03;51(1):383.
    PMID: 38433142 DOI: 10.1007/s11033-024-09324-9
    BACKGROUND: Graphene oxide (GO) is widespread in scaffold engineering owing to its extraordinary properties such as multiple oxygen functional groups, high hydrophilicity ability and biocompatibility. It is known to promote differentiation in mesenchymal stem cells, but concomitant comparison of its modulation on the expression profiles of Wharton's jelly (WJ)-MSC surface markers, lineage differentiation, and epigenetic regulatory genes in basal and induced condition are still lacking. Unraveling the fundamental mechanisms is essential for the effective utilization of WJ-MSCs incorporated with GO in therapy. This study aims to explore the unique gene expression profiles and epigenetic characteristics of WJ-MSCs influenced by GO.

    METHODS AND RESULTS: The characterized GO-coated coverslip served as a substrate for culturing WJ-MSCs. In addition to investigating the impact of GO on cell proliferation and differentiation, we conducted a gene expression study using PCR array, while epigenetic control was assessed through bisulfite sequencing and Western blot analysis. Our findings indicate that the presence of GO maintained the proliferation and survival of WJ-MSCs. In the absence of induction, GO led to minor lipid and glycosaminoglycan deposition in WJ-MSCs. This was evidenced by the sustained expression of pluripotency and lineage-specific genes, demethylation at the OCT4 promoter, and a decrease in H3K9 methylation. In osteo-induced condition, the occurrence of osteogenesis appeared to be guided by BMP/TGF and ERK pathway activation, accompanied by the upregulation of osteogenic-related genes and downregulation of DNMT3b.

    CONCLUSIONS: GO in osteo-induced condition create a favorable microenvironment that promotes the osteogenesis of WJ-MSCs by influencing genetic and epigenetic controls. This helps in advancing our knowledge on the use of GO as priming platform and WJ-MSCs an alternate source for bone repair and regeneration.

    Matched MeSH terms: Mesenchymal Stromal Cells*
  19. Noor Azlan NAB, Vitus V, Nor Rashid N, Nordin F, Tye GJ, Wan Kamarul Zaman WS
    Cell Tissue Res, 2024 Mar;395(3):227-250.
    PMID: 38244032 DOI: 10.1007/s00441-023-03857-4
    The promising field of regenerative medicine is thrilling as it can repair and restore organs for various debilitating diseases. Mesenchymal stem cells are one of the main components in regenerative medicine that work through the release of secretomes. By adopting the use of the secretome in cell-free-based therapy, we may be able to address the challenges faced in cell-based therapy. As one of the components of cell-free-based therapy, secretome has the advantage of a better safety and efficacy profile than mesenchymal stem cells. However, secretome has its challenges that need to be addressed, such as its bioprocessing methods that may impact the secretome content and its mechanisms of action in clinical settings. Effective and standardization of bioprocessing protocols are important to ensure the supply and sustainability of secretomes for clinical applications. This may eventually impact its commercialization and marketability. In this review, the bioprocessing methods and their impacts on the secretome profile and treatment are discussed. This improves understanding of its fundamental aspects leading to potential clinical applications.
    Matched MeSH terms: Mesenchymal Stromal Cells*
  20. Chakraborty S, Ong WK, Yau WWY, Zhou Z, Bhanu Prakash KN, Toh SA, et al.
    Stem Cell Res Ther, 2021 02 04;12(1):109.
    PMID: 33541392 DOI: 10.1186/s13287-021-02179-y
    BACKGROUND: Effective stem cell therapy is dependent on the stem cell quality that is determined by their differentiation potential, impairment of which leads to poor engraftment and survival into the target cells. However, limitations in our understanding and the lack of reliable markers that can predict their maturation efficacies have hindered the development of stem cells as an effective therapeutic strategy. Our previous study identified CD10, a pro-adipogenic, depot-specific prospective cell surface marker of human adipose-derived stem cells (ASCs). Here, we aim to determine if CD10 can be used as a prospective marker to predict mature adipocyte quality and play a direct role in adipocyte maturation.

    METHODS: We first generated 14 primary human subject-derived ASCs and stable immortalized CD10 knockdown and overexpression lines for 4 subjects by the lentiviral transduction system. To evaluate the role of CD10 in adipogenesis, the adipogenic potential of the human subject samples were scored against their respective CD10 transcript levels. Assessment of UCP1 expression levels was performed to correlate CD10 levels to the browning potential of mature ASCs. Quantitative polymerase chain reaction (qPCR) and Western blot analysis were performed to determine CD10-dependent regulation of various targets. Seahorse analysis of oxidative metabolism and lipolysis assay were studied. Lastly, as a proof-of-concept study, we used CD10 as a prospective marker for screening nuclear receptor ligands library.

    RESULTS: We identified intrinsic CD10 levels as a positive determinant of adipocyte maturation as well as browning potential of ASCs. Interestingly, CD10 regulates ASC's adipogenic maturation non-canonically by modulating endogenous lipolysis without affecting the classical peroxisome proliferator-activated receptor gamma (PPARγ)-dependent adipogenic pathways. Furthermore, our CD10-mediated screening analysis identified dexamethasone and retinoic acid as stimulator and inhibitor of adipogenesis, respectively, indicating CD10 as a useful biomarker for pro-adipogenic drug screening.

    CONCLUSION: Overall, we establish CD10 as a functionally relevant ASC biomarker, which may be a prerequisite to identify high-quality cell populations for improving metabolic diseases.

    Matched MeSH terms: Cells, Cultured; Stem Cells
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