Displaying publications 161 - 180 of 247 in total

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  1. Biomimetic hydroxyapatite/poly xylitol sebacic adibate/vitamin K nanocomposite for enhancing bone regeneration
    Dai Z, Dang M, Zhang W, Murugan S, Teh SW, Pan H
    Artif Cells Nanomed Biotechnol, 2019 Dec;47(1):1898-1907.
    PMID: 31066314 DOI: 10.1080/21691401.2019.1573183
    Hydroxyapatite (HAP) is a significant bone mineral that establishes bone strength. HAP composites in combination with biodegradable and bioactive polymer poly xylitol sebacic adipate (PXSA) would result in a constant release at target sites. Numerous studies have shown that vitamin K (VK) might possess a vital function in bone metabolism. The purpose of the present study was to inspect the synthesized composite HAP/PXSA/VK in developing polymeric biomaterials composite for the application of bone tissue regeneration. FTIR, X-ray diffraction, SEM and TEM techniques were applied to characterize the prepared composites. The release of VK from the HAP/PXSA/VK composite was evidenced through UV-Vis spectroscopy. In vitro studies proved that the HAP/PXSA/VK composite is appropriate for mesenchymal stem cell culture. Compared to pure HAP prepared following the same method, HAP/PXSA/VK composite provided favourable microstructures and good biodegradation distinctiveness for the application of tissue engineering, as well as tissue in-growth characteristics and improved scaffold cell penetration. This work reveals that the HAP/PXSA/VK composites have the potential for applications in bone tissue engineering.
    Matched MeSH terms: Mesenchymal Stromal Cells
  2. Fulltext Advancing towards Effective Glioma Therapy: MicroRNA Derived from Umbilical Cord Mesenchymal Stem Cells' Extracellular Vesicles
    Ngadiono E, Hardiany NS
    Malays J Med Sci, 2019 Jul;26(4):5-16.
    PMID: 31496889 DOI: 10.21315/mjms2019.26.4.2
    A glioma, especially a grade IV glioblastoma, is a malignant tumour with a poor prognosis despite growing medical advancements. Researchers have been looking for better and more effective treatments targeting the molecular pathways of gliomas due to glioblastomas' ability to develop resistance to chemotherapies. Moreover, glioma stem cells (GSC) contribute to maintaining the glioma population, which benefits from its ability to self-renew and differentiate. Recent research has reported that through the introduction of umbilical cord mesenchymal stem cells (UCMSC) into glioma cells, the growth and development of the glioma cells can be downregulated. It has more currently been found out that UCMSC release extracellular vesicles (EVs) containing miRNA that are responsible for this phenomenon. Therefore, this review analyses literature to discuss all possible miRNAs contained within the UCMSC's EVs and to elaborate on their molecular mechanisms in halting gliomas and GSC growth. This review will also include the challenges and limitations, to account for which more in vivo research is suggested. In conclusion, this review highlights how miRNAs contained within UCMSC's EVs are able to downregulate multiple prominent pathways in the survival of gliomas.
    Matched MeSH terms: Mesenchymal Stromal Cells
  3. Fulltext Repair of segmental load-bearing bone defect by autologous mesenchymal stem cells and plasma-derived fibrin impregnated ceramic block results in early recovery of limb function
    Ng MH, Duski S, Tan KK, Yusof MR, Low KC, Rose IM, et al.
    Biomed Res Int, 2014;2014:345910.
    PMID: 25165699 DOI: 10.1155/2014/345910
    Calcium phosphate-based bone substitutes have not been used to repair load-bearing bone defects due to their weak mechanical property. In this study, we reevaluated the functional outcomes of combining ceramic block with osteogenic-induced mesenchymal stem cells and platelet-rich plasma (TEB) to repair critical-sized segmental tibial defect. Comparisons were made with fresh marrow-impregnated ceramic block (MIC) and partially demineralized allogeneic bone block (ALLO). Six New Zealand White female rabbits were used in each study group and three rabbits with no implants were used as negative controls. By Day 90, 4/6 rabbits in TEB group and 2/6 in ALLO and MIC groups resumed normal gait pattern. Union was achieved significantly faster in TEB group with a radiological score of 4.50 ± 0.78 versus ALLO (1.06 ± 0.32), MIC (1.28 ± 0.24), and negative controls (0). Histologically, TEB group scored the highest percentage of new bone (82% ± 5.1%) compared to ALLO (5% ± 2.5%) and MIC (26% ± 5.2%). Biomechanically, TEB-treated tibiae achieved the highest compressive strength (43.50 ± 12.72 MPa) compared to those treated with ALLO (15.15 ± 3.57 MPa) and MIC (23.28 ± 6.14 MPa). In conclusion, TEB can repair critical-sized segmental load-bearing bone defects and restore limb function.
    Matched MeSH terms: Mesenchymal Stromal Cells/chemistry*
  4. Fulltext Hypoxic culture conditions as a solution for mesenchymal stem cell based regenerative therapy
    Haque N, Rahman MT, Abu Kasim NH, Alabsi AM
    ScientificWorldJournal, 2013;2013:632972.
    PMID: 24068884 DOI: 10.1155/2013/632972
    Cell-based regenerative therapies, based on in vitro propagation of stem cells, offer tremendous hope to many individuals suffering from degenerative diseases that were previously deemed untreatable. Due to the self-renewal capacity, multilineage potential, and immunosuppressive property, mesenchymal stem cells (MSCs) are considered as an attractive source of stem cells for regenerative therapies. However, poor growth kinetics, early senescence, and genetic instability during in vitro expansion and poor engraftment after transplantation are considered to be among the major disadvantages of MSC-based regenerative therapies. A number of complex inter- and intracellular interactive signaling systems control growth, multiplication, and differentiation of MSCs in their niche. Common laboratory conditions for stem cell culture involve ambient O₂ concentration (20%) in contrast to their niche where they usually reside in 2-9% O₂. Notably, O₂ plays an important role in maintaining stem cell fate in terms of proliferation and differentiation, by regulating hypoxia-inducible factor-1 (HIF-1) mediated expression of different genes. This paper aims to describe and compare the role of normoxia (20% O₂) and hypoxia (2-9% O₂) on the biology of MSCs. Finally it is concluded that a hypoxic environment can greatly improve growth kinetics, genetic stability, and expression of chemokine receptors during in vitro expansion and eventually can increase efficiency of MSC-based regenerative therapies.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
  5. Cord blood-derived mesenchymal stem cell does not stimulate nor inhibits T lymphocytes activation
    Tong CK, Seow HF, Ramasamy R
    Med J Malaysia, 2008 Jul;63 Suppl A:77-8.
    PMID: 19024992
    The immune modulatory properties of mesenchymal stem cell (MSC) had brought a new insight in cell-based neotherapy. However, recent works of MSC are focused exclusively on bone marrow-derived MSC. We evaluated the immunogenicity of cord blood-derived MSC (CB-MSC) on T lymphocytes. Human peripheral blood mononuclear cells (PBMC) were prepared by density gradient separation and culture with the presence or absence of CB-MSC. PBMC were collected for activation analysis by flow cytometry at 24-, 48-, and 72- hours. The results showed that, CB-MSC does not stimulate nor inhibit T lymphocyte activation.
    Matched MeSH terms: Mesenchymal Stromal Cells/immunology*
  6. Isolation techniques of murine bone marrow progenitor cells and their adipogenic, neurogenic and osteogenic differentiation capacity
    Ng AM, Kojima K, Kodoma S, Ruszymah BH, Aminuddin BS, Vacanti AC
    Med J Malaysia, 2008 Jul;63 Suppl A:121-2.
    PMID: 19025015
    Bone marrow derived progenitor cells have been widely studied for its multipotent property and have proofed to be an important resource in regenerative medicine. However, the propagation of murine bone marrow appeared to be a great challenge as compared to other mammalian species. In this study, various isolation techniques and the plasticity of the isolated cells were evaluated. Our result shows that magnetic sorting technique yielded the most viable cells and displayed wider differentiation capacity.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
  7. In vitro differences of hydroxyapatite from different resources in simulated body fluid
    Hashim N, Sabudin S, Ibrahim S, Zin NM, Bakar SH, Fazan F
    Med J Malaysia, 2004 May;59 Suppl B:103-4.
    PMID: 15468839
    Hydroxyapatite (HA; Ca10(PO4)6(OH)2), is one of the significant implant materials used in Orthopaedics and Dental applications. However, synthetically produced HA may not be stable under ionic environment, which it will unavoidably encounter during its applications. In this paper, the in vitro effects of three HA materials derived from different resources, i.e. commercial HA (HAC), synthesised HA from pure chemicals (HAS) and synthesised HA from kapur sireh; derived traditionally from natural limestone (HAK), were studied. The HA disc samples were prepared and immersed in simulated body fluid (SBF) for 31-day period. The evaluation conducted focuses on the changes of the pH and the Calcium ion (Ca-ion) and Phosphate ion (P-ion) concentrations in the SBF solution, as well as the XRD and SEM data representing the reactions on the HA materials. From the XRD, it was found that HAK has the smallest crystallite sizes, which in turn affect the pH of the SBF during immersion. The Ca and P-ion concentrations generally decrease over time at different rates for different HA. Upon 1-day immersion in SBF, apatite growth was observed onto all three surfaces, which became more pronounced after 3-day immersion. However, the appetites formed were observed to be different in shapes and sizes. The reasons for the difference in the apatite-crystals and their subsequent effects on cells are still being investigated.
    Matched MeSH terms: Mesenchymal Stromal Cells/drug effects*
  8. Bone marrow mesenchymal stem cells differentiation and proliferation on the surface of coral implant
    Al-Salihi KA, Samsudin AR
    Med J Malaysia, 2004 May;59 Suppl B:45-6.
    PMID: 15468811
    This study was designed to evaluate the ability of natural coral implant to provide an environment for marrow cells to differentiate into osteoblasts and function suitable for mineralized tissue formation. DNA content, alkaline phosptatase (ALP) activity, calcium (Ca) content and mineralized nodules, were measured at day 3, day 7 and day 14, in rat bone marrow stromal cells cultured with coral discs glass discs, while cells alone and coral disc alone were cultured as control. DNA content, ALP activity, Ca content measurements showed no difference between coral, glass and cells groups at 3 day which were higher than control (coral disc alone), but there were higher measurement at day 7 and 14 in the cell cultured on coral than on glass discs, control cells and control coral discs. Mineralized nodules formation (both in area and number) was more predominant on the coral surface than in control groups. These results showed that natural coral implant provided excellent and favorable situation for marrow cell to differentiate to osteoblasts, lead to large amount of mineralized tissue formation on coral surface. This in vitro result could explain the rapid bone bonding of coral in vivo.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
  9. Autologous human fibrin as the biomaterial for tissue engineering
    Ruszymah BH
    Med J Malaysia, 2004 May;59 Suppl B:30-1.
    PMID: 15468804
    Patient own fibrin may act as the safest, cheapest and immediate available biodegradable scaffold material in clinical 1 tissue engineering. This study investigated the feasibility of using patient own fibrin isolated from whole blood to construct a new human cartilage, skin and bone. Constructed in vitro tissues were implanted on the dorsal part of the nude mice for in vivo maturation. After 8 weeks of implantation, the engineered tissues were removed for histological analysis. Our results demonstrated autologous fibrin has great potential as clinical scaffold material to construct various human tissues.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology
  10. Neurogenic plasticity of mesenchymal stem cell, an alluring cellular replacement for traumatic brain injury
    Pati S, Muthuraju S, Hadi RA, Huat TJ, Singh S, Maletic-Savatic M, et al.
    Curr Stem Cell Res Ther, 2016;11(2):149-57.
    PMID: 26763886
    Traumatic brain injury (TBI) imposes horrendous neurophysiological alterations leading to most devastating forms of neuro-disability. Which includes impaired cognition, distorted locomotors activity and psychosomatic disability in both youths and adults. Emerging evidence from recent studies has identified mesenchymal stem cells (MSCs) as one of the promising category of stem cells having excellent neuroregenerative capability in TBI victims. Some of the clinical and animal studies reported that MSCs transplantation could cure neuronal damage as well as improve cognitive and locomotors behaviors in TBI. However, mechanism behind their broad spectrum neuroregenerative potential in TBI has not been reviewed yet. Therefore, in the present article, we present a comprehensive data on the important attributes of MSCs, such as neurotransdifferentiation, neuroprotection, axonal repair and plasticity, maintenance of blood-brain integrity, reduction of reactive oxygen species (ROS) and immunomodulation. We have reviewed in detail the crucial neurogenic capabilities of MSCs in vivo and provided consolidated knowledge regarding their cellular remodeling in TBI for future therapeutic implications.
    Matched MeSH terms: Mesenchymal Stromal Cells*
  11. Proliferation and osteogenic differentiation of mesenchymal stromal cells in a novel porous hydroxyapatite scaffold
    Krishnamurithy G, Murali MR, Hamdi M, Abbas AA, Raghavendran HB, Kamarul T
    Regen Med, 2015;10(5):579-90.
    PMID: 26237702 DOI: 10.2217/rme.15.27
    To compare the effect of bovine bone derived porous hydroxyapatite (BDHA) scaffold on proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hMSCs) compared with commercial hydroxyapatite (CHA) scaffold.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
  12. Microenvironmental factors involved in human amnion mesenchymal stem cells fate decisions
    Syva SH, Ampon K, Lasimbang H, Fatimah SS
    J Tissue Eng Regen Med, 2017 02;11(2):311-320.
    PMID: 26073746 DOI: 10.1002/term.2043
    Human amnion mesenchymal stem cells (HAMCs) show great differentiation and proliferation potential and also other remarkable features that could serve as an outstanding alternative source of stem cells in regenerative medicine. Recent reports have demonstrated various kinds of effective artificial niche that mimic the microenvironment of different types of stem cell to maintain and control their fate and function. The components of the stem cell microenvironment consist mainly of soluble and insoluble factors responsible for regulating stem cell differentiation and self-renewal. Extensive studies have been made on regulating HAMCs differentiation into specific phenotypes; however, the understanding of relevant factors in directing stem cell fate decisions in HAMCs remain underexplored. In this review, we have therefore identified soluble and insoluble factors, including mechanical stimuli and cues from the other supporting cells that are involved in directing HAMCs fate decisions. In order to strengthen the significance of understanding on the relevant factors involved in stem cell fate decisions, recent technologies developed to specifically mimic the microenvironments of specific cell lineages are also reviewed. Copyright © 2015 John Wiley & Sons, Ltd.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
  13. Effects of mechanical loading on human mesenchymal stem cells for cartilage tissue engineering
    Choi JR, Yong KW, Choi JY
    J Cell Physiol, 2018 Mar;233(3):1913-1928.
    PMID: 28542924 DOI: 10.1002/jcp.26018
    Today, articular cartilage damage is a major health problem, affecting people of all ages. The existing conventional articular cartilage repair techniques, such as autologous chondrocyte implantation (ACI), microfracture, and mosaicplasty, have many shortcomings which negatively affect their clinical outcomes. Therefore, it is essential to develop an alternative and efficient articular repair technique that can address those shortcomings. Cartilage tissue engineering, which aims to create a tissue-engineered cartilage derived from human mesenchymal stem cells (MSCs), shows great promise for improving articular cartilage defect therapy. However, the use of tissue-engineered cartilage for the clinical therapy of articular cartilage defect still remains challenging. Despite the importance of mechanical loading to create a functional cartilage has been well demonstrated, the specific type of mechanical loading and its optimal loading regime is still under investigation. This review summarizes the most recent advances in the effects of mechanical loading on human MSCs. First, the existing conventional articular repair techniques and their shortcomings are highlighted. The important parameters for the evaluation of the tissue-engineered cartilage, including chondrogenic and hypertrophic differentiation of human MSCs are briefly discussed. The influence of mechanical loading on human MSCs is subsequently reviewed and the possible mechanotransduction signaling is highlighted. The development of non-hypertrophic chondrogenesis in response to the changing mechanical microenvironment will aid in the establishment of a tissue-engineered cartilage for efficient articular cartilage repair.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
  14. Cytoprotective effects of antioxidant supplementation on mesenchymal stem cell therapy
    Panahi M, Rahimi B, Rahimi G, Yew Low T, Saraygord-Afshari N, Alizadeh E
    J Cell Physiol, 2020 10;235(10):6462-6495.
    PMID: 32239727 DOI: 10.1002/jcp.29660
    Mesenchymal stem cells (MSCs) are earmarked as perfect candidates for cell therapy and tissue engineering due to their capacity to differentiate into different cell types. However, their potential for application in regenerative medicine declines when the levels of the reactive oxygen and nitrogen species (RONS) increase from the physiological levels, a phenomenon which is at least inevitable in ex vivo cultures and air-exposed damaged tissues. Increased levels of RONS can alter the patterns of osteogenic and adipogenic differentiation and inhibit proliferation, as well. Besides, oxidative stress enhances senescence and cell death, thus lowering the success rates of the MSC engraftment. Hence, in this review, we have selected some representatives of antioxidants and newly emerged nano antioxidants in three main categories, including chemical compounds, biometabolites, and protein precursors/proteins, which are proved to be effective in the treatment of MSCs. We will focus on how antioxidants can be applied to optimize the clinical usage of the MSCs and their associated signaling pathways. We have also reviewed several paralleled properties of some antioxidants and nano antioxidants which can be simultaneously used in real-time imaging, scaffolding techniques, and other applications in addition to their primary antioxidative function.
    Matched MeSH terms: Mesenchymal Stromal Cells/drug effects*
  15. Fulltext Human Mesenchymal Stem Cells-mediated Transcriptomic Regulation of Leukemic Cells in Delivering Anti-tumorigenic Effects
    Sarmadi VH, Ahmadloo S, Boroojerdi MH, John CM, Al-Graitte SJR, Lawal H, et al.
    Cell Transplant, 2020 2 7;29:963689719885077.
    PMID: 32024378 DOI: 10.1177/0963689719885077
    Treatment of leukemia has become much difficult because of resistance to the existing anticancer therapies. This has thus expedited the search for alternativ therapies, and one of these is the exploitation of mesenchymal stem cells (MSCs) towards control of tumor cells. The present study investigated the effect of human umbilical cord-derived MSCs (UC-MSCs) on the proliferation of leukemic cells and gauged the transcriptomic modulation and the signaling pathways potentially affected by UC-MSCs. The inhibition of growth of leukemic tumor cell lines was assessed by proliferation assays, apoptosis and cell cycle analysis. BV173 and HL-60 cells were further analyzed using microarray gene expression profiling. The microarray results were validated by RT-qPCR and western blot assay for the corresponding expression of genes and proteins. The UC-MSCs attenuated leukemic cell viability and proliferation in a dose-dependent manner without inducing apoptosis. Cell cycle analysis revealed that the growth of tumor cells was arrested at the G0/G1 phase. The microarray results identified that HL-60 and BV173 share 35 differentially expressed genes (DEGs) (same expression direction) in the presence of UC-MSCs. In silico analysis of these selected DEGs indicated a significant influence in the cell cycle and cell cycle-related biological processes and signaling pathways. Among these, the expression of DBF4, MDM2, CCNE2, CDK6, CDKN1A, and CDKN2A was implicated in six different signaling pathways that play a pivotal role in the anti-tumorigenic activity exerted by UC-MSCs. The UC-MSCs perturbate the cell cycle process of leukemic cells via dysregulation of tumor suppressor and oncogene expression.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism*
  16. In vitro differentiation of mesenchymal stem cells into mesangial cells when co-cultured with injured mesangial cells
    Wong CY, Tan EL, Cheong SK
    Cell Biol Int, 2014 Apr;38(4):497-501.
    PMID: 24375917 DOI: 10.1002/cbin.10231
    Mesangial cells are one of the three major cell types of the kidney glomerulus that provide physical support for the glomerular capillary lumen of the kidney. Loss of mesangial cells due to pathologic conditions, such as glomerulonephritis and diabetic nephropathy, can impair renal function. Mesenchymal stem cells (MSC) are attractive candidates for kidney repair therapy since they can enhance recovery and protect against kidney failure. MSC can differentiate into mesangial cells in vivo. We have investigated the ability of MSC to differentiate into mesangial cells in vitro; they were co-cultured with oxidant-injured mesangial cells before being analysed by flow cytometry and for contractility. MSC co-cultured with injured mesangial cells had a mesangial cell-like morphology and contracted in response to angiotensin II. They expressed CD54(-) CD62E(+) in direct contrast to the CD54(+) CD62E(-) of pure MSC. In conclusion, MSC can differentiate into mesangial cells in vitro when co-cultured with injured mesangial cells.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
  17. Fulltext Human mesenchymal stem cells inhibit the differentiation and effector functions of monocytes
    Maqbool M, Algraittee SJR, Boroojerdi MH, Sarmadi VH, John CM, Vidyadaran S, et al.
    Innate Immun, 2020 07;26(5):424-434.
    PMID: 32635840 DOI: 10.1177/1753425919899132
    Although monocytes represent an essential part of the host defence system, their accumulation and prolonged stimulation could be detrimental and may aggravate chronic inflammatory diseases. The present study has explored the less-understood immunomodulatory effects of mesenchymal stem cells on monocyte functions. Isolated purified human monocytes were co-cultured with human umbilical cord-derived mesenchymal stem cells under appropriate culture conditions to assess monocytes' vital functions. Based on the surface marker analysis, mesenchymal stem cells halted monocyte differentiation into dendritic cells and macrophages and reduced their phagocytosis functions, which rendered an inability to stimulate T-cell proliferation. The present study confers that mesenchymal stem cells exerted potent immunosuppressive activity on monocyte functions such as differentiation, phagocytosis and Ag presentation; hence, they promise a potential therapeutic role in down-regulating the unwanted monocyte-mediated immune responses in the context of chronic inflammatory diseases.
    Matched MeSH terms: Mesenchymal Stromal Cells/physiology*
  18. Development of multisubstituted hydroxyapatite nanopowders as biomedical materials for bone tissue engineering applications
    Baba Ismail YM, Wimpenny I, Bretcanu O, Dalgarno K, El Haj AJ
    J Biomed Mater Res A, 2017 Jun;105(6):1775-1785.
    PMID: 28198131 DOI: 10.1002/jbm.a.36038
    Ionic substitutions have been proposed as a tool to control the functional behavior of synthetic hydroxyapatite (HA), particularly for Bone Tissue Engineering applications. The effect of simultaneous substitution of different levels of carbonate (CO3) and silicon (Si) ions in the HA lattice was investigated. Furthermore, human bone marrow-derived mesenchymal stem cells (hMSCs) were cultured on multi-substituted HA (SiCHA) to determine if biomimetic chemical compositions were osteoconductive. Of the four different compositions investigates, SiCHA-1 (0.58 wt % Si) and SiCHA-2 (0.45 wt % Si) showed missing bands for CO3and Si using FTIR analysis, indicating competition for occupation of the phosphate site in the HA lattice; 500°C was considered the most favorable calcination temperature as: (i) the powders produced possessed a similar amount of CO3(2-8 wt %) and Si (<1.0 wt %) as present in native bone; and (ii) there was a minimal loss of CO3and Si from the HA structure to the surroundings during calcination. Higher Si content in SiCHA-1 led to lower cell viability and at most hindered proliferation, but no toxicity effect occurred. While, lower Si content in SiCHA-2 showed the highest ALP/DNA ratio after 21 days culture with hMSCs, indicating that the powder may stimulate osteogenic behavior to a greater extent than other powders. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1775-1785, 2017.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology
  19. Fulltext Mesenchymal Stem Cell Expressing TRAIL as Targeted Therapy against Sensitised Tumour
    Fakiruddin KS, Ghazalli N, Lim MN, Zakaria Z, Abdullah S
    Int J Mol Sci, 2018 07 27;19(8).
    PMID: 30060445 DOI: 10.3390/ijms19082188
    Tapping into the ability of engineered mesenchymal stem cells (MSCs) to mobilise into the tumour has expanded the scope of cancer treatment. Engineered MSCs expressing tumour necrosis factor (TNF)-related apoptosis inducing ligand (MSC-TRAIL) could serve as a platform for an efficient and targeted form of therapy. However, the presence of cancer stem cells (CSCs) that are resistant to TRAIL and apoptosis may represent a challenge for effective treatment. Nonetheless, with the discovery of small molecular inhibitors that could target CSCs and tumour signalling pathways, a higher efficacy of MSC-TRAIL mediated tumour inhibition can be achieved. This might pave the way for a more effective form of combined therapy, which leads to a better treatment outcome. In this review, we first discuss the tumour-homing capacity of MSCs, its effect in tumour tropism, the different approach behind genetically-engineered MSCs, and the efficacy and safety of each agent delivered by these MSCs. Then, we focus on how sensitisation of CSCs and tumours using small molecular inhibitors can increase the effect of these cells to either TRAIL or MSC-TRAIL mediated inhibition. In the conclusion, we address a few questions and safety concerns regarding the utilization of engineered MSCs for future treatment in patients.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism*
  20. Fulltext Selective activation of miRNAs of the primate-specific chromosome 19 miRNA cluster (C19MC) in cancer and stem cells and possible contribution to regulation of apoptosis
    Nguyen PN, Huang CJ, Sugii S, Cheong SK, Choo KB
    J Biomed Sci, 2017 Mar 07;24(1):20.
    PMID: 28270145 DOI: 10.1186/s12929-017-0326-z
    BACKGROUND: The human chromosome 19 miRNA cluster (C19MC) of 43 genes is a primate-specific miRNA cluster that may have biological significance in the genetic complexity of the primate. Despite previous reports on individual C19MC miRNA expression in cancer and stem cells, systematic studies on C19MC miRNA expression and biological functions are lacking.

    RESULTS: Cluster-wide C19MC miRNA expression profiling by microarray analysis showed wholesome C19MC activation in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). However, in multipotent adipose-derived mesenchymal stem cells (MSCs) and a unipotent human white pre-adipocyte cell line, only selected C19MC miRNAs were expressed. MiRNA copy number analysis also showed selective C19MC expression in cancer cells with expression patterns highly similar to those in MSCs, suggesting similar miRNA regulatory mechanisms in these cells. Selective miRNA expression also suggests complex transcriptional mechanism(s) regulating C19MC expression under specific cellular and pathological conditions. Bioinformatics analysis showed that sixteen of the C19MC miRNAs share the same "AAGUGC" seed sequence with members of the miR-302/-372 family, which are known cellular reprogramming factors. In particular, C19MC-AAGUGC-miRNAs with the nucleotides 2-7 canonical seed position as in miR-302/-372 miRNAs, may play similar roles as miR-302/-372 in induced pluripotency. A biased 3p-arm selection of the C19MC-AAGUGC-miRNAs was observed indicating that targets of the 3p species of these miRNAs may be biologically significant in regulating stemness. Furthermore, bioinformatics analysis of the putative targets of the C19MC-AAGUGC-miRNAs predicted significant involvement of signaling pathways in reprogramming, many of which contribute to promoting apoptosis by indirect activation of the pro-apoptotic proteins BAK/BAX via suppression of genes of the cell survival pathways, or by enhancing caspase-8 activation through targeting inhibitors of TRAIL-inducing apoptosis.

    CONCLUSIONS: This work demonstrated selective C19MC expression in MSCs and cancer cells, and, through miRNA profiling and bioinformatics analysis, predicted C19MC modulation of apoptosis in induced pluripotency and tumorigenesis.

    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism
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