Displaying publications 61 - 80 of 3287 in total

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  1. Bone marrow-derived mesenchymal stem cells: A promising therapeutic option for the treatment of diabetic foot ulcers
    Dama G, Du J, Zhu X, Liu Y, Lin J
    Diabetes Res Clin Pract, 2023 Jan;195:110201.
    PMID: 36493913 DOI: 10.1016/j.diabres.2022.110201
    Chronic wounds fail to heal through the three normal stages of healing (inflammatory, proliferative, and remodelling), resulting in a chronic tissue injury that is not repaired within the average time limit. Patients suffering from type 1 and type 2 diabetes are prone to develop diabetic foot ulcers (DFUs), which commonly develop into chronic wounds that are non treatable with conventional therapies. DFU develops due to various risk factors, such as peripheral neuropathy, peripheral vascular disease, arterial insufficiency, foot deformities, trauma and impaired resistance to infection. DFUs have gradually become a major problem in the health care system worldwide. In this review, we not only focus on the pathogenesis of DFU but also comprehensively summarize the outcomes of preclinical and clinical studies thus far and the potential therapeutic mechanism of bone marrow-derived mesenchymal stem cells (BMSCs) for the treatment of DFU. Based on the published results, BMSC transplantation can contribute to wound healing through growth factor secretion, anti-inflammation, differentiation into tissue-specific cells, neovascularization, re-epithelialization and angiogenesis in DFUs. Moreover, clinical trials showed that BMSC treatment in patients with diabetic ulcers improved ulcer healing and the ankle-brachial index, ameliorated pain scores, and enhanced claudication walking distances with no reported complications. In conclusion, although BMSC transplantation exhibits promising therapeutic potential in DFU treatment, additional studies should be performed to confirm their efficacy and long-term safety in DFU patients.
    Matched MeSH terms: Mesenchymal Stromal Cells*
  2. Detection of Circulating Tumor Cells and Epithelial Progenitor Cells: A Comprehensive Study
    Fuloria S, Subramaniyan V, Gupta G, Sekar M, Meenakshi DU, Sathasivam K, et al.
    J Environ Pathol Toxicol Oncol, 2023;42(3):1-29.
    PMID: 37017676 DOI: 10.1615/JEnvironPatholToxicolOncol.2022044456
    Technological advancement to enhance tumor cells (TC) has allowed discovery of various cellular bio-markers: cancer stem cells (CSC), circulating tumor cells (CTC), and endothelial progenitor cells (EPC). These are responsible for resistance, metastasis, and premetastatic conditions of cancer. Detection of CSC, CTC, and EPC assists in early diagnosis, recurrence prediction, and treatment efficacy. This review describes various methods to detect TC subpopulations such as in vivo assays (sphere-forming, serial dilution, and serial transplantation), in vitro assays (colony-forming cells, microsphere, side-population, surface antigen staining, aldehyde dehydrogenase activity, and Paul Karl Horan label-retaining cells, surface markers, nonenriched and enriched detection), reporter systems, and other analytical methods (flow cytometry, fluorescence microscopy/spectroscopy, etc.). The detailed information on methods to detect CSC, CTC, and EPC in this review will assist investigators in successful prognosis, diagnosis, and cancer treatment with greater ease.
    Matched MeSH terms: Neoplastic Stem Cells/pathology
  3. Fulltext Hope on the horizon: Wharton's jelly mesenchymal stem cells in the fight against COVID-19
    Gupta G, Hussain MS, Thapa R, Dahiya R, Mahapatra DK, Bhat AA, et al.
    Regen Med, 2023 Sep;18(9):675-678.
    PMID: 37554111 DOI: 10.2217/rme-2023-0077
    Matched MeSH terms: Mesenchymal Stromal Cells*
  4. Fulltext Melanin pigment of Streptomyces puniceus RHPR9 exhibits antibacterial, antioxidant and anticancer activities
    Polapally R, Mansani M, Rajkumar K, Burgula S, Hameeda B, Alhazmi A, et al.
    PLoS One, 2022;17(4):e0266676.
    PMID: 35468144 DOI: 10.1371/journal.pone.0266676
    The present study reveals the production of dark, extracellular melanin pigment (386 mg/L) on peptone yeast extract iron agar medium by Streptomyces puniceus RHPR9 using the gravimetric method. UV-Visible, Fourier Transform Infrared (FTIR), and Nuclear Magnetic Resonance (1H) (NMR) spectroscopy confirmed the presence of melanin. Extracted melanin showed antibacterial activity against human pathogens such as Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli except for Klebsiella pneumoniae. A potent free radical scavenging activity was observed at 100 μg/mL of melanin by the DPPH method with a concentration of 89.01±0.05% compared with ascorbic acid 96.16±0.01%. Antitumor activity of melanin was evaluated by MTT assay against HEK 293, HeLa, and SK-MEL-28 cell lines with IC50 values of 64.11±0.00, 14.43±0.02, and 13.31±0.01 μg/mL respectively. Melanin showed maximum anti-inflammatory activity with human red blood cells (hRBC) (78.63 ± 0.01%) and minimum hemolysis of 21.37±0.2%. The wound healing potential of the pigment was confirmed on HeLa cells, cell migration was calculated, and it was observed that cell migration efficiency decreased with an increase in the concentration of melanin. To our knowledge, this is the first evidence of melanin produced from S. puniceus RHPR9 that exhibited profound scavenging, anti-inflammatory and cytotoxic activities.
    Matched MeSH terms: HeLa Cells; HEK293 Cells
  5. Revolutionizing colorectal cancer treatment: unleashing the potential of miRNAs in targeting cancer stem cells
    Osei GY, Adu-Amankwaah J, Koomson S, Beletaa S, Ahmad MK, Asiamah EA, et al.
    Future Oncol, 2023 Nov;19(35):2369-2382.
    PMID: 37970643 DOI: 10.2217/fon-2023-0426
    Colorectal cancer (CRC) is a significant contributor to cancer mortality worldwide, and the presence of cancer stem cells (CSC) represents a major challenge for achieving effective treatment. miRNAs have emerged as critical regulators of gene expression, and recent studies have highlighted their role in regulating stemness and therapeutic resistance in CRC stem cells. This review highlights the mechanisms of CSC development, therapy resistance and the potential of miRNAs as therapeutic targets for CRC. It emphasizes the promise of miRNAs as a novel approach to CRC treatment and calls for further research to explore effective miRNA-based therapies and strategies for delivering miRNAs to CSCs in vivo.
    Matched MeSH terms: Neoplastic Stem Cells/metabolism
  6. Human cytokeratin 1 plays a role in the interaction of Pteropine orthoreovirus with Hek293 cells but not HeLa cells
    Siew ZY, Tan YF, Iswara RP, Wong SF, Wong ST, Tan BK, et al.
    Microbes Infect, 2024;26(1-2):105243.
    PMID: 38380604 DOI: 10.1016/j.micinf.2023.105243
    Pteropine orthoreovirus (PRV) causes respiratory tract infections in humans. Despite its emergence as a zoonotic and respiratory virus, little is known about its cell tropism, which hampers progress in fully understanding its pathogenesis in humans. Hek293 cells are most susceptible to PRV infection, while HeLa cells are the least. Human cytokeratin 1 (CK1) was identified as the protein that interacts with PRV. The immunofluorescence assay and qPCR results revealed prior treatment with anti-CK1 may provide Hek293 cells protection against PRV. The KRT1-knockout Hek293 cells were less susceptible to PRV infection. Further study into the pathogenesis of PRV in humans is needed.
    Matched MeSH terms: HeLa Cells; HEK293 Cells
  7. Dielectric properties of urine in relation to bladder cancer
    Zhu CZ, Ting HN, Ng KH, Mun KS, Ong TA
    Phys Eng Sci Med, 2024 Mar;47(1):61-71.
    PMID: 37843766 DOI: 10.1007/s13246-023-01341-5
    Many studies have investigated the dielectric properties of human and animal tissues, particularly to differentiate between normal cells and tumors. However, these studies are invasive as tissue samples have to be excised to measure the properties. This study aims to investigate the dielectric properties of urine in relation to bladder cancer, which is safe and non-invasive to patients. 30 healthy subjects and 30 bladder cancer patients were recruited. Their urine samples were subjected to urinalysis and cytology assessment. A vector network analyzer was used to measure the dielectric constant (Ɛ') and loss factor (Ɛ″) at microwave frequencies of between 0.2 and 50 GHz at 25 °C, 30 °C and 37 °C. Significant differences in Ɛ' and Ɛ″ were observed between healthy subjects and patients, especially at frequencies of between 25 and 40 GHz at 25 °C. Bladder cancer patients had significant lower Ɛ' and higher Ɛ″ compared with healthy subjects. The Ɛ' was negatively correlated with urinary exfoliated urothelial cell number, and Ɛ″ was positively correlated. The study achieved a receiver operating characteristic area under curve (ROC-AUC) score of 0.69099 and an optimum accuracy of 75% with a sensitivity of 80% and a specificity of 70%. The number of exfoliated urothelial cell had significant effect on the dielectric properties, especially in bladder cancer patients. Urinary dielectric properties could potentially be used as a tool to detect bladder cancer.
    Matched MeSH terms: Epithelial Cells/pathology
  8. Mesenchymal stem cells in the management of oral submucous fibrosis-An enigma to be solved
    Kizhakkoottu S, Ramani P, Tilakaratne WM
    J Oral Pathol Med, 2024 May;53(5):275-276.
    PMID: 38685571 DOI: 10.1111/jop.13539
    Matched MeSH terms: Mesenchymal Stromal Cells*
  9. Estrogen receptor alpha mediates 17β-estradiol, up-regulates autophagy and alleviates hydrogen peroxide-induced vascular senescence
    Xiang X, Xie L, Lin J, Pare R, Huang G, Huang J, et al.
    Biogerontology, 2023 Oct;24(5):783-799.
    PMID: 36683095 DOI: 10.1007/s10522-023-10015-4
    Atherosclerosis threatens human health by developing cardiovascular diseases, the deadliest disease world widely. The major mechanism contributing to the formation of atherosclerosis is mainly due to vascular endothelial cell (VECs) senescence. We have shown that 17β-estradiol (17β-E2) may protect VECs from senescence by upregulating autophagy. However, little is known about how 17β-E2 activates the autophagy pathway to alleviate cellular senescence. Therefore, the aim of this study is to determine the role of estrogen receptor (ER) α and β in the effects of 17β-E2 on vascular autophagy and aging through in vitro and in vivo models. Hydrogen peroxide (H2O2) was used to establish Human Umbilical Vein Endothelial Cells (HUVECs) senescence. Autophagy activity was measured through immunofluorescence and immunohistochemistry staining of light chain 3 (LC3) expression. Inhibition of ER activity was established using shRNA gene silencing and ER antagonist. Compared with ER-β knockdown, we found that knockdown of ER-α resulted in a significant increase in the extent of HUVEC senescence and senescence-associated secretory phenotype (SASP) secretion. ER-α-specific shRNA was found to reduce 17β-E2-induced autophagy, promote HUVEC senescence, disrupt the morphology of HUVECs, and increase the expression of Rb dephosphorylation and SASP. These in vitro findings were found consistent with the in vivo results. In conclusion, our data suggest that 17β-E2 activates the activity of ER-α and then increases the formation of autophagosomes (LC3 high expression) and decreases the fusion of lysosomes with autophagic vesicles (P62 low expression), which in turn serves to decrease the secretion of SASP caused by H2O2 and consequently inhibit H2O2-induced senescence in HUVEC cells.
    Matched MeSH terms: Cells, Cultured; Human Umbilical Vein Endothelial Cells
  10. Application of Platelet-Rich Plasma as a Stem Cell Treatment - an Attempt to Clarify a Common Public Misconception
    Fareez IM, Liew FF, Widera D, Mayeen NF, Mawya J, Abu Kasim NH, et al.
    Curr Mol Med, 2024;24(6):689-701.
    PMID: 37171013 DOI: 10.2174/1566524023666230511152646
    In recent years, there has been a significant increase in the practice of regenerative medicine by health practitioners and direct-to-consumer businesses globally. Among different tools of regenerative medicine, platelet-rich plasma (PRP) and stem cell-based therapies have received considerable attention. The use of PRP, in particular, has gained popularity due to its easy access, simple processing techniques, and regenerative potential. However, it is important to address a common misconception amongst the general public equating to PRP and stem cells due to the demonstrated efficacy of PRP in treating musculoskeletal and dermatological disorders. Notably, PRP promotes regeneration by providing growth factors or other paracrine factors only. Therefore, it cannot replenish or replace the lost cells in conditions where a large number of cells are required to regenerate tissues and/or organs. In such cases, cellbased therapies are the preferred option. Additionally, other tools of regenerative medicine, such as bioprinting, organoids, and mechanobiology also rely on stem cells for their success. Hence, healthcare and commercial entities offering direct-to-customer regenerative therapies should not mislead the public by claiming that the application of PRP is a stem cell-based therapy. Furthermore, it is important for regulatory bodies to strictly monitor these profit-driven entities to prevent them from providing unregulated regenerative treatments and services that claim a broad variety of benefits with little proof of efficacy, safety concerns, and obscure scientific justification.
    Matched MeSH terms: Stem Cells/cytology
  11. Spermatogonial Stem Cells Protein Identification in In Vitro Culture from Non-Obstructive Azoospermia Patient
    Abdul Wahab AY, Md Isa ML, Ramli R
    Malays J Med Sci, 2016 May;23(3):40-8.
    PMID: 27418868
    Spermatogonial stem cells (SSCs) are classifiedas a unique adult stem cells that have capability to propagate, differentiate, and transmit genetic information to the next generation. Studies on human SSCs may help resolve male infertility problems, especially in azoospermia patients. Therefore, this study aims to propagate SSCs in-vitro with a presence of growth factor and detect SSC-specific protein cell surface markers.
    Matched MeSH terms: Adult Stem Cells; Adult Germline Stem Cells
  12. Fulltext Frequent co-expression of miRNA-5p and -3p species and cross-targeting in induced pluripotent stem cells
    Huang CJ, Nguyen PN, Choo KB, Sugii S, Wee K, Cheong SK, et al.
    Int J Med Sci, 2014;11(8):824-33.
    PMID: 24936146 DOI: 10.7150/ijms.8358
    A miRNA precursor generally gives rise to one major miRNA species derived from the 5' arm, and are called miRNA-5p. However, more recent studies have shown co-expression of miRNA-5p and -3p, albeit in different concentrations, in cancer cells targeting different sets of transcripts. Co-expression and regulation of the -5p and -3p miRNA species in stem cells, particularly in the reprogramming process, have not been studied.
    Matched MeSH terms: Embryonic Stem Cells/metabolism*; Induced Pluripotent Stem Cells/metabolism*; Mesenchymal Stromal Cells/metabolism*
  13. Generation of induced pluripotent stem cells by a polycistronic lentiviral vector in feeder- and serum- free defined culture
    Al Abbar A, Nordin N, Ghazalli N, Abdullah S
    Tissue Cell, 2018 Dec;55:13-24.
    PMID: 30503056 DOI: 10.1016/j.tice.2018.09.004
    Induced pluripotent stem cells (iPSCs) have great potentials for regenerative medicine. However, serious concerns such as the use of the viral-mediated reprogramming strategies and exposure of iPSCs to animal products from feeder cells and serum-containing medium have restricted the application of iPSCs in the clinics. Therefore, the generation of iPSCs with minimal viral integrations and in non-animal sourced and serum-free medium is necessary. In this report, a polycistronic lentiviral vector carrying Yamanaka's factors was used to reprogram mouse fibroblasts into iPSCs in feeder- and xeno-free culture environment. The generated iPSCs exhibited morphology and self-renewal properties of embryonic stem cells (ESCs), expression of specific pluripotent markers, and potentials to differentiate into the three-major distinct specialized germ layers in vitro. The iPSCs were also shown to have the potential to differentiate into neural precursor and neurons in culture, with greater than 95% expression of nestin, Pax6 and βIII-tubulin. This body of work describes an alternative method of generating iPSCs by using polycistronic lentiviral vector that may minimize the risks associated with viral vector-mediated reprogramming and animal derived products in the culture media.
    Matched MeSH terms: Embryonic Stem Cells/cytology*; Induced Pluripotent Stem Cells/cytology*; Feeder Cells/cytology*
  14. Fulltext Isolation, characterization and the multi-lineage differentiation potential of rabbit bone marrow-derived mesenchymal stem cells
    Tan SL, Ahmad TS, Selvaratnam L, Kamarul T
    J Anat, 2013 Apr;222(4):437-50.
    PMID: 23510053 DOI: 10.1111/joa.12032
    Mesenchymal stem cells (MSCs) are recognized by their plastic adherent ability, fibroblastic-like appearance, expression of specific surface protein markers, and are defined by their ability to undergo multi-lineage differentiation. Although rabbit bone marrow-derived MSCs (rbMSCs) have been used extensively in previous studies especially in translational research, these cells have neither been defined morphologically and ultrastructurally, nor been compared with their counterparts in humans in their multi-lineage differentiation ability. A study was therefore conducted to define the morphology, surface marker proteins, ultrastructure and multi-lineage differentiation ability of rbMSCs. Herein, the primary rbMSC cultures of three adult New Zealand white rabbits (at least 4 months old) were used for three independent experiments. rbMSCs were isolated using the gradient-centrifugation method, an established technique for human MSCs (hMSCs) isolation. Cells were characterized by phase contrast microscopy observation, transmission electron microscopy analysis, reverse transcriptase-polymerase chain reaction (PCR) analysis, immunocytochemistry staining, flow cytometry, alamarBlue(®) assay, histological staining and quantitative (q)PCR analysis. The isolated plastic adherent cells were in fibroblastic spindle-shape and possessed eccentric, irregular-shaped nuclei as well as rich inner cytoplasmic zones similar to that of hMSCs. The rbMSCs expressed CD29, CD44, CD73, CD81, CD90 and CD166, but were negative (or dim positive) for CD34, CD45, CD117 and HLD-DR. Despite having similar morphology and phenotypic expression, rbMSCs possessed significantly larger cell size but had a lower proliferation rate as compared with hMSCs. Using established protocols to differentiate hMSCs, rbMSCs underwent osteogenic, adipogenic and chondrogenic differentiation. Interestingly, differentiated rbMSCs demonstrated higher levels of osteogenic (Runx2) and chondrogenic (Sox9) gene expressions than that of hMSCs (P  0.05). rbMSCs possess similar morphological characteristics to hMSCs, but have a higher potential for osteogenic and chondrogenic differentiation, despite having a lower cell proliferation rate than hMSCs. The characteristics reported here may be used as a comprehensive set of criteria to define or characterize rbMSCs.
    Matched MeSH terms: Bone Marrow Cells/cytology*; Mesenchymal Stromal Cells/cytology*; Mesenchymal Stromal Cells/physiology; Mesenchymal Stromal Cells/ultrastructure
  15. Human Pluripotent Stem Cell Culture on Polyvinyl Alcohol-Co-Itaconic Acid Hydrogels with Varying Stiffness Under Xeno-Free Conditions
    Sung TC, Li HF, Higuchi A, Ling QD, Yang JS, Tseng YC, et al.
    J Vis Exp, 2018 02 03.
    PMID: 29443075 DOI: 10.3791/57314
    The effect of physical cues, such as the stiffness of biomaterials on the proliferation and differentiation of stem cells, has been investigated by several researchers. However, most of these investigators have used polyacrylamide hydrogels for stem cell culture in their studies. Therefore, their results are controversial because those results might originate from the specific characteristics of the polyacrylamide and not from the physical cue (stiffness) of the biomaterials. Here, we describe a protocol for preparing hydrogels, which are not based on polyacrylamide, where various stem, cells including human embryonic stem (ES) cells and human induced pluripotent stem (iPS) cells, can be cultured. Hydrogels with varying stiffness were prepared from bioinert polyvinyl alcohol-co-itaconic acid (P-IA), with stiffness controlled by crosslinking degree by changing crosslinking time. The P-IA hydrogels grafted with and without oligopeptides derived from extracellular matrix were investigated as a future platform for stem cell culture and differentiation. The culture and passage of amniotic fluid stem cells, adipose-derived stem cells, human ES cells, and human iPS cells is described in detail here. The oligopeptide P-IA hydrogels showed superior performances, which were induced by their stiffness properties. This protocol reports the synthesis of the biomaterial, their surface manipulation, along with controlling the stiffness properties and finally, their impact on stem cell fate using xeno-free culture conditions. Based on recent studies, such modified substrates can act as future platforms to support and direct the fate of various stem cells line to different linkages; and further, regenerate and restore the functions of the lost organ or tissue.
    Matched MeSH terms: Cells, Cultured; Pluripotent Stem Cells/cytology; Pluripotent Stem Cells/metabolism*; Induced Pluripotent Stem Cells/cytology
  16. Autogenic feeder free system from differentiated mesenchymal progenitor cells, maintains pluripotency of the MEL-1 human embryonic stem cells
    Khoo TS, Hamidah Hussin N, Then SM, Jamal R
    Differentiation, 2013 Feb;85(3):110-8.
    PMID: 23722082 DOI: 10.1016/j.diff.2013.01.004
    Human embryonic stem cells (hESc) are known for its pluripotency and self renewal capability, thus possess great potential in regenerative medicine. However, the lack of suitable xenofree extracellular matrix substrate inhibits further applications or the use of hESc in cell-based therapy. In this study, we described a new differentiation method, which generates a homogeneous population of mesenchymal progenitor cells (hESc-MPC) from hESc via epithelial-mesenchymal transition. The extracellular matrix (ECM) proteins from hESc-MPC had in turn supported the undifferentiated expansion of hESc. Immunocytochemistry and flow cytometry characterization of hESc-MPC revealed the presence of early mesenchymal markers. Tandem mass spectometry analysis of ECM produced by hESc-MPC revealed the presence of a mixture of extracellular proteins which includes tenascin C, fibronectin, and vitronectin. The pluripotency of hESc (MEL-1) cultured on the ECM was maintained as shown by the expression of pluripotent genes (FoxD3, Oct-4, Tdgf1, Sox-2, Nanog, hTERT, Rex1), protein markers (SSEA-3, SSEA-4, TRA-1-81, TRA-1-60, Oct-4) and the ability to differentiate into cells representative of ectoderm, endoderm and mesoderm. In summary, we have established a xeno-free autogenic feeder free system to support undifferentiated expansion of hESc, which could be of clinical relevance.
    Matched MeSH terms: Pluripotent Stem Cells/cytology; Pluripotent Stem Cells/metabolism; Embryonic Stem Cells/cytology*; Mesenchymal Stromal Cells/cytology*; Mesenchymal Stromal Cells/drug effects; Feeder Cells/cytology*
  17. Fulltext Transfected human mesenchymal stem cells do not lose their surface markers and differentiation properties
    Yap FL, Cheong SK, Ammu R, Leong CF
    Malays J Pathol, 2009 Dec;31(2):113-20.
    PMID: 20514854 MyJurnal
    In this study, we evaluated the biological properties of human mesenchymal stem cells transfected (hMSC) with a plasmid vector expressing human cytokine interleukin-12 (IL-12). Surface markers were analysed by immunophenotyping using flow cytometry. Differentiation capability was evaluated towards adipogenesis and osteogenesis. We demonstrated that successfully transfected hMSC retained their surface immunophenotypes and differentiation potential into adipocytes and osteocytes. These results indicate that hMSC may be a suitable vehicle for gene transduction.
    Matched MeSH terms: Bone Marrow Cells/cytology; Bone Marrow Cells/metabolism; Cells, Cultured; Mesenchymal Stromal Cells/cytology*; Mesenchymal Stromal Cells/metabolism
  18. 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: Cells, Cultured; Hematopoietic Stem Cells/drug effects*; Hematopoietic Stem Cells/metabolism; Mesenchymal Stromal Cells/drug effects*; Mesenchymal Stromal Cells/metabolism
  19. Fulltext Decoding the differentiation of mesenchymal stem cells into mesangial cells at the transcriptomic level
    Wong CY, Chang YM, Tsai YS, Ng WV, Cheong SK, Chang TY, et al.
    BMC Genomics, 2020 Jul 07;21(1):467.
    PMID: 32635896 DOI: 10.1186/s12864-020-06868-5
    BACKGROUND: Mesangial cells play an important role in the glomerulus to provide mechanical support and maintaine efficient ultrafiltration of renal plasma. Loss of mesangial cells due to pathologic conditions may lead to impaired renal function. Mesenchymal stem cells (MSC) can differentiate into many cell types, including mesangial cells. However transcriptomic profiling during MSC differentiation into mesangial cells had not been studied yet. The aim of this study is to examine the pattern of transcriptomic changes during MSC differentiation into mesangial cells, to understand the involvement of transcription factor (TF) along the differentiation process, and finally to elucidate the relationship among TF-TF and TF-key gene or biomarkers during the differentiation of MSC into mesangial cells.

    RESULTS: Several ascending and descending monotonic key genes were identified by Monotonic Feature Selector. The identified descending monotonic key genes are related to stemness or regulation of cell cycle while ascending monotonic key genes are associated with the functions of mesangial cells. The TFs were arranged in a co-expression network in order of time by Time-Ordered Gene Co-expression Network (TO-GCN) analysis. TO-GCN analysis can classify the differentiation process into three stages: differentiation preparation, differentiation initiation and maturation. Furthermore, it can also explore TF-TF-key genes regulatory relationships in the muscle contraction process.

    CONCLUSIONS: A systematic analysis for transcriptomic profiling of MSC differentiation into mesangial cells has been established. Key genes or biomarkers, TFs and pathways involved in differentiation of MSC-mesangial cells have been identified and the related biological implications have been discussed. Finally, we further elucidated for the first time the three main stages of mesangial cell differentiation, and the regulatory relationships between TF-TF-key genes involved in the muscle contraction process. Through this study, we have increased fundamental understanding of the gene transcripts during the differentiation of MSC into mesangial cells.

    Matched MeSH terms: Cells, Cultured; Mesangial Cells/metabolism*; Mesangial Cells/physiology; Mesenchymal Stromal Cells/cytology; Mesenchymal Stromal Cells/metabolism*
  20. Genetically-modified human mesenchymal stem cells to express erythropoietin enhances differentiation into retinal photoreceptors: An in-vitro study
    Ding SLS, Koh AE, Kumar S, Ali Khan MS, Alzahrani B, Mok PL
    J. Photochem. Photobiol. B, Biol., 2019 Jun;195:33-38.
    PMID: 31060031 DOI: 10.1016/j.jphotobiol.2019.04.008
    Dysfunctional or death of retinal photoreceptors is an irreversible phenomenon that is closely associated with a broad range of retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration (AMD), resulting in successive loss of visual function and blindness. In search for viable treatment for retinal degenerative diseases, mesenchymal stem cells (MSCs) has demonstrated promising therapeutic capabilities to repair and replace damaged photoreceptor cells in both in vitro and in vivo conditions. Nevertheless, the dearth of MSC differentiation capacity into photoreceptors has limited its use in cell replacement therapy. Erythropoietin (EPO) has vital role in early neural retinal cell differentiation and demonstrated rescue potential on dying photoreceptor cells. Hence, we aimed to evaluate the differentiation capacity of MSCs into photoreceptor cells in the presence of human EPO protein. We derived the MSC from human Wharton's jelly of umbilical cord and transduced the cells with lentivirus particles encoding EPO and green fluorescent protein (GFP) as reporter gene. The transduced cells were selectively cultured and induced to differentiate into photoreceptors by exposing to photoreceptor differentiation cocktail. Our preliminary results showed that transduced cells exposed to induction medium had an enhanced differentiation capacity when compared to non-transduced cells. Our results demonstrated a novel strategy to increase the yield of in vitro photoreceptor differentiation and may be potentially useful in improving the efficiency of stem cell transplantation for ocular disorders.
    Matched MeSH terms: Cells, Cultured; Photoreceptor Cells, Vertebrate/cytology; Photoreceptor Cells, Vertebrate/metabolism*; Mesenchymal Stromal Cells/cytology; Mesenchymal Stromal Cells/metabolism*
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