Displaying publications 81 - 100 of 145 in total

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  1. Almasi D, Iqbal N, Sadeghi M, Sudin I, Abdul Kadir MR, Kamarul T
    Int J Biomater, 2016;2016:8202653.
    PMID: 27127513 DOI: 10.1155/2016/8202653
    There is an increased interest in the use of polyether ether ketone (PEEK) for orthopedic and dental implant applications due to its elastic modulus close to that of bone, biocompatibility, and its radiolucent properties. However, PEEK is still categorized as bioinert due to its low integration with surrounding tissues. Many studies have reported on methods to increase the bioactivity of PEEK, but there is still one-preparation method for preparing bioactive PEEK implant where the produced implant with desirable mechanical and bioactivity properties is required. The aim of this review is to present the progress of the preparation methods for improvement of the bioactivity of PEEK and to discuss the strengths and weaknesses of the existing methods.
  2. Ibrahim MR, Singh S, Merican AM, Raghavendran HR, Murali MR, Naveen SV, et al.
    BMC Vet Res, 2016 Jun 16;12(1):112.
    PMID: 27307015 DOI: 10.1186/s12917-016-0724-6
    Fracture healing in bone gap is one of the major challenges encountered in Orthopedic Surgery. At present, the treatment includes bone graft, employing either internal or external fixation which has a significant impact on the patient, family and even society. New drugs are emerging in the markets such as anabolic bone-forming agents including teriparatide and strontium ranelate to stimulate bone growth. Based on the mechanism of their actions, we embarked on a study on the healing of a fractured ulna with bone gap in a rabbit model. We segregated ten rabbits into two groups: five rabbits in the test group and five rabbits in the control group. We created a 5 mm bone gap in the ulna bone, removing the periosteum as well. Rabbits in the test group received 450 mg/kg of strontium ranelate via oral administration, daily, for six weeks. The x-rays, CT scans and blood tests were performed every two weeks. At the end of six weeks, the rabbits were sacrificed, and the radius and ulna bones harvested for histopathological examination.
  3. Wahab AH, Kadir MR, Harun MN, Kamarul T, Syahrom A
    Med Biol Eng Comput, 2017 Mar;55(3):439-447.
    PMID: 27255451 DOI: 10.1007/s11517-016-1525-6
    The present study was conducted to compare the stability of four commercially available implants by investigating the focal stress distributions and relative micromotion using finite element analysis. Variations in the numbers of pegs between the implant designs were tested. A load of 750 N was applied at three different glenoid positions (SA: superior-anterior; SP: superior-posterior; C: central) to mimic off-center and central loadings during activities of daily living. Focal stress distributions and relative micromotion were measured using Marc Mentat software. The results demonstrated that by increasing the number of pegs from two to five, the total focal stress volumes exceeding 5 MPa, reflecting the stress critical volume (SCV) as the threshold for occurrence of cement microfractures, decreased from 8.41 to 5.21 % in the SA position and from 9.59 to 6.69 % in the SP position. However, in the C position, this change in peg number increased the SCV from 1.37 to 5.86 %. Meanwhile, micromotion appeared to remain within 19-25 µm irrespective of the number of pegs used. In conclusion, four-peg glenoid implants provide the best configuration because they had lower SCV values compared with lesser-peg implants, preserved more bone stock, and reduced PMMA cement usage compared with five-peg implants.
  4. Karunanithi P, Murali MR, Samuel S, Raghavendran HRB, Abbas AA, Kamarul T
    Carbohydr Polym, 2016 08 20;147:294-303.
    PMID: 27178935 DOI: 10.1016/j.carbpol.2016.03.102
    Presence of sulfated polysaccharides like heparan sulphate has often been implicated in the regulation of chondrogenesis. However, recently there has been a plethora of interest in the use of non-animal extracted analogs of heparan sulphate. Here we remodeled alginate (1.5%) by incorporating fucoidan (0.5%), a natural sulphated polysaccharide extracted from seaweeds to form a composite hydrogel (Al-Fu), capable of enhancing chondrogenesis of human mesenchymal stromal cells (hMSCs). We confirmed the efficiency of fucoidan incorporation by FTIR and EDX analysis. Further, its ability to support hMSC attachment and chondrogenic differentiation was confirmed by SEM, biochemical glycosaminoglycan quantification, real-time quantitative PCR and immunocytochemical analyses of chondrogenic markers Sox-9, Collagen II, Aggrecan and COMP. Effect of Al-Fu hydrogel on hMSC hypertrophy was also confirmed by the downregulation of hypertrophic genes Collagen X and Runx2. This composite scaffold can hence be used as a cartilage biomimetic biomaterial to drive hMSC chondrogenesis and for other cartilage repair based therapies.
  5. Chadda H, Naveen SV, Mohan S, Satapathy BK, Ray AR, Kamarul T
    J Prosthet Dent, 2016 Jul;116(1):129-35.
    PMID: 26873771 DOI: 10.1016/j.prosdent.2015.12.013
    STATEMENT OF PROBLEM: Although the physical and mechanical properties of hydroxyapatite-filled dental restorative composite resins have been examined, the biocompatibility of these materials has not been studied in detail.

    PURPOSE: The purpose of this in vitro study was to analyze the toxicity of acrylate-based restorative composite resins filled with hydroxyapatite and a silica/hydroxyapatite combination.

    MATERIAL AND METHODS: Five different restorative materials based on bisphenol A-glycidyl methacrylate (bis-GMA) and tri-ethylene glycol dimethacrylate (TEGDMA) were developed: unfilled (H0), hydroxyapatite-filled (H30, H50), and silica/hydroxyapatite-filled (SH30, SH50) composite resins. These were tested for in vitro cytotoxicity by using human bone marrow mesenchymal stromal cells. Surface morphology, elemental composition, and functional groups were determined by scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDX), and Fourier-transformed infrared spectroscopy (FTIR). The spectra normalization, baseline corrections, and peak integration were carried out by OPUS v4.0 software.

    RESULTS: Both in vitro cytotoxicity results and SEM analysis indicated that the composite resins developed were nontoxic and supported cell adherence. Elemental analysis with EDX revealed the presence of carbon, oxygen, calcium, silicon, and gold, while the presence of methacrylate, hydroxyl, and methylene functional groups was confirmed through FTIR analysis.

    CONCLUSIONS: The characterization and compatibility studies showed that these hydroxyapatite-filled and silica/hydroxyapatite-filled bis-GMA/TEGDMA-based restorative composite resins are nontoxic to human bone marrow mesenchymal stromal cells and show a favorable biologic response, making them potential biomaterials.

  6. 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.
  7. Nouri F, Salehinejad P, Nematollahi-Mahani SN, Kamarul T, Zarrindast MR, Sharifi AM
    Cell Mol Neurobiol, 2016 Jul;36(5):689-700.
    PMID: 26242172 DOI: 10.1007/s10571-015-0249-8
    Transplantation of neural-like cells is considered as a promising therapeutic strategy developed for neurodegenerative disease in particular for ischemic stroke. Since cell survival is a major concern following cell implantation, a number of studies have underlined the protective effects of preconditioning with hypoxia or hypoxia mimetic pharmacological agents such as deferoxamine (DFO), induced by activation of hypoxia inducible factor-1 (HIF-1) and its target genes. The present study has investigated the effects of DFO preconditioning on some factors involved in cell survival, angiogenesis, and neurogenesis of neural-like cells derived from human Wharton's jelly mesenchymal stem cells (HWJ-MSCs) in presence of hydrogen peroxide (H2O2). HWJ-MSCs were differentiated toward neural-like cells for 14 days and neural cell markers were identified using immunocytochemistry. HWJ-MSC-derived neural-like cells were then treated with 100 µM DFO, as a known hypoxia mimetic agent for 48 h. mRNA and protein expression of HIF-1 target genes including brain-derived neurotrophic factors (BDNF) and vascular endothelial growth factor (VEGF) significantly increased using RT-PCR and Western blotting which were reversed by HIF-1α inhibitor, while, gene expression of Akt-1, Bcl-2, and Bax did not change significantly but pAkt-1 was up-regulated as compared to poor DFO group. However, addition of H2O2 to DFO-treated cells resulted in higher resistance to H2O2-induced cell death. Western blotting analysis also showed significant up-regulation of HIF-1α, BDNF, VEGF, and pAkt-1, and decrease of Bax/Bcl-2 ratio as compared to poor DFO. These results may suggest that DFO preconditioning of HWJ-MSC-derived neural-like cells improves their tolerance and therapeutic potential and might be considered as a valuable strategy to improve cell therapy.
  8. Fatihhi SJ, Harun MN, Abdul Kadir MR, Abdullah J, Kamarul T, Öchsner A, et al.
    Ann Biomed Eng, 2015 Oct;43(10):2487-502.
    PMID: 25828397 DOI: 10.1007/s10439-015-1305-8
    Fatigue assessment of the trabecular bone has been developed to give a better understanding of bone properties. While most fatigue studies are relying on uniaxial compressive load as the method of assessment, in various cases details are missing, or the uniaxial results are not very realistic. In this paper, the effect of three different load histories from physiological loading applied on the trabecular bone were studied in order to predict the first failure surface and the fatigue lifetime. The fatigue behaviour of the trabecular bone under uniaxial load was compared to that of multiaxial load using a finite element simulation. The plastic strain was found localized at the trabecular structure under multiaxial load. On average, applying multiaxial loads reduced more than five times the fatigue life of the trabecular bone. The results provide evidence that multiaxial loading is dominated in the low cycle fatigue in contrast to the uniaxial one. Both bone volume fraction and structural model index were best predictors of failure (p 
  9. Dashtdar H, Rothan HA, Tay T, Ahmad RE, Ali R, Tay LX, et al.
    J Orthop Res, 2011 Sep;29(9):1336-42.
    PMID: 21445989 DOI: 10.1002/jor.21413
    Chondrogenic differentiated mesenchymal stem cells (CMSCs) have been shown to produce superior chondrogenic expression markers in vitro. However, the use of these cells in vivo has not been fully explored. In this study, in vivo assessment of cartilage repair potential between allogenic-derived chondrogenic pre-differentiated mesenchymal stem cells and undifferentiated MSCs (MSCs) were compared. Bilateral full thickness cartilage defects were created on the medial femoral condyles of 12 rabbits (n = 12). Rabbits were divided into two groups. In one group, the defects in the right knees were repaired using alginate encapsulated MSCs while in the second group, CMSCs were used. The animals were sacrificed and the repaired and control knees were assessed at 3 and 6 months after implantation. Quantitative analysis was performed by measuring the Glycosaminoglycans (GAGs)/total protein content. The mean Brittberg score was higher in the transplanted knees as compared to the untreated knee at 6 months (p  0.05). This study demonstrates that the use of either MSC or CMSC produced superior healing when compared to cartilage defects that were untreated. However, both cells produced comparable treatment outcomes.
  10. Mehrabani M, Najafi M, Kamarul T, Mansouri K, Iranpour M, Nematollahi MH, et al.
    Cell Prolif, 2015 Oct;48(5):532-49.
    PMID: 26332145 DOI: 10.1111/cpr.12209
    OBJECTIVES: Both excessive and insufficient angiogenesis are associated with progression of diabetic complications, of which poor angiogenesis is an important feature. Currently, adipose-derived stem cells (ADSCs) are considered to be a promising source to aid therapeutic neovascularization. However, functionality of these cells is impaired by diabetes which can result from a defect in hypoxia-inducible factor-1 (HIF-1), a key mediator involved in neovascularization. In the current study, we sought to explore effectiveness of pharmacological priming with deferoxamine (DFO) as a hypoxia mimetic agent, to restore the compromised angiogenic pathway, with the aid of ADSCs derived from streptozotocin (STZ)-induced type 1 diabetic rats ('diabetic ADSCs').

    MATERIALS AND METHODS: Diabetic ADSCs were treated with DFO and compared to normal and non-treated diabetic ADSCs for expression of HIF-1α, VEGF, FGF-2 and SDF-1, at mRNA and protein levels, using qRT-PCR, western blotting and ELISA assay. Activity of matrix metalloproteinases -2 and -9 were measured using a gelatin zymography assay. Angiogenic potential of conditioned media derived from normal, DFO-treated and non-treated diabetic ADSCs were determined by in vitro (in HUVECs) and in vivo experiments including scratch assay, three-dimensional tube formation testing and surgical wound healing models.

    RESULTS: DFO remarkably enhanced expression of noted genes by mRNA and protein levels and restored activity of matrix metalloproteinases -2 and -9. Compromised angiogenic potential of conditioned medium derived from diabetic ADSCs was restored by DFO both in vitro and in vivo experiments.

    CONCLUSION: DFO preconditioning restored neovascularization potential of ADSCs derived from diabetic rats by affecting the HIF-1α pathway.

  11. Tan HY, Tan SL, Teo SH, Roebuck MM, Frostick SP, Kamarul T
    PeerJ, 2020;8:e8740.
    PMID: 32587790 DOI: 10.7717/peerj.8740
    Background: Type 2 diabetes mellitus (T2DM) had been reported to be associated with tendinopathy. However, the underlying mechanisms of diabetic tendinopathy still remain largely to be discovered. The purpose of this study was to develop insulin resistance (IR) model on primary human tenocytes (hTeno) culture with tumour necrosis factor-alpha (TNF-α) treatment to study tenocytes homeostasis as an implication for diabetic tendinopathy.

    Methods: hTenowere isolated from human hamstring tendon. Presence of insulin receptor beta (INSR-β) on normal tendon tissues and the hTeno monolayer culture were analyzed by immunofluorescence staining. The presence of Glucose Transporter Type 1 (GLUT1) and Glucose Transporter Type 4 (GLUT4) on the hTeno monolayer culture were also analyzed by immunofluorescence staining. Primary hTeno were treated with 0.008, 0.08, 0.8 and 8.0 µM of TNF-α, with and without insulin supplement. Outcome measures include 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) assay to determine the glucose uptake activity; colourimetric total collagen assay to quantify the total collagen expression levels; COL-I ELISA assay to measure the COL-I expression levels and real-time qPCR to analyze the mRNA gene expressions levels of Scleraxis (SCX), Mohawk (MKX), type I collagen (COL1A1), type III collagen (COL3A1), matrix metalloproteinases (MMP)-9 and MMP-13 in hTeno when treated with TNF-α. Apoptosis assay for hTeno induced with TNF-α was conducted using Annexin-V FITC flow cytometry analysis.

    Results: Immunofluorescence imaging showed the presence of INSR-β on the hTeno in the human Achilles tendon tissues and in the hTeno in monolayer culture. GLUT1 and GLUT4 were both positively expressed in the hTeno. TNF-α significantly reduced the insulin-mediated 2-NBDG uptake in all the tested concentrations, especially at 0.008 µM. Total collagen expression levels and COL-I expression levels in hTeno were also significantly reduced in hTeno treated with 0.008 µM of TNF-α. The SCX, MKX and COL1A1 mRNA expression levels were significantly downregulated in all TNF-α treated hTeno, whereas the COL3A1, MMP-9 and MMP-13 were significantly upregulated in the TNF-α treated cells. TNF-α progressively increased the apoptotic cells at 48 and 72 h.

    Conclusion: At 0.008 µM of TNF-α, an IR condition was induced in hTeno, supported with the significant reduction in glucose uptake, as well as significantly reduced total collagen, specifically COL-I expression levels, downregulation of candidate tenogenic markers genes (SCX and MKX), and upregulation of ECM catabolic genes (MMP-9 and MMP-13). Development of novel IR model in hTeno provides an insight on how tendon homeostasis could be affected and can be used as a tool for further discovering the effects on downstream molecular pathways, as the implication for diabetic tendinopathy.

  12. Tai L, Huang CJ, Choo KB, Cheong SK, Kamarul T
    Int J Med Sci, 2020;17(4):457-470.
    PMID: 32174776 DOI: 10.7150/ijms.38832
    Oxidative stress has been linked to senescence and tumorigenesis via modulation of the cell cycle. Using a hydrogen peroxide (H2O2)-induced oxidative stress-induced premature senescence (OSIPS) model previously reported by our group, this study aimed to investigate the effects of oxidative stress on microRNA (miRNA) expression in relation to the G1-to-S-phase (G1/S) transition of the cell cycle and cell proliferation. On global miRNA analysis of the OSIPS cells, twelve significantly up- or down-regulated miRNAs were identified, the target genes of which are frequently associated with cancers. Four down-regulated miR-17 family miRNAs are predicted to target key pro- and anti-proliferative proteins of the p21/cyclin D-dependent kinase (CDK)/E2F1 pathway to modulate G1/S transition. Two miR-17 miRNAs, miR-20-5p and miR-106-5p, were confirmed to be rapidly and stably down-regulated under oxidative stress. While H2O2 treatment hampered G1/S transition and suppressed DNA synthesis, miR-20b-5p/miR-106a-5p over-expression rescued cells from growth arrest in promoting G1/S transition and DNA synthesis. Direct miR-20b-5p/miR-106a-5p regulation of p21, CCND1 and E2F1 was demonstrated by an inverse expression relationship in miRNA mimic-transfected cells. However, under oxidative stress, E2F1 expression was down-regulated, consistent with hampered G1/S transition and suppressed DNA synthesis and cell proliferation. To explain the observed E2F1 down-regulation under oxidative stress, a scheme is proposed which includes miR-20b-5p/miR-106a-5p-dependent regulation, miRNA-E2F1 autoregulatory feedback and E2F1 response to repair oxidative stress-induced DNA damages. The oxidative stress-modulated expression of miR-17 miRNAs and E2F1 may be used to develop strategies to retard or reverse MSC senescence in culture, or senescence in general.
  13. Alizadeh M, Kadir MR, Fadhli MM, Fallahiarezoodar A, Azmi B, Murali MR, et al.
    J Orthop Res, 2013 Sep;31(9):1447-54.
    PMID: 23640802 DOI: 10.1002/jor.22376
    Posterior instrumentation is a common fixation method used to treat thoracolumbar burst fractures. However, the role of different cross-link configurations in improving fixation stability in these fractures has not been established. A 3D finite element model of T11-L3 was used to investigate the biomechanical behavior of short (2 level) and long (4 level) segmental spine pedicle screw fixation with various cross-links to treat a hypothetical L1 vertebra burst fracture. Three types of cross-link configurations with an applied moment of 7.5 Nm and 200 N axial force were evaluated. The long construct was stiffer than the short construct irrespective of whether the cross-links were used (p < 0.05). The short constructs showed no significant differences between the cross-link configurations. The XL cross-link provided the highest stiffness and was 14.9% stiffer than the one without a cross-link. The long construct resulted in reduced stress to the adjacent vertebral bodies and screw necks, with 66.7% reduction in bending stress on L2 when the XL cross-link was used. Thus, the stability for L1 burst fracture fixation was best achieved by using long segmental posterior instrumentation constructs and an XL cross-link configuration. Cross-links did not improved stability when a short structure was used.
  14. Nam HY, Murali MR, Ahmad RE, Pingguan-Murphy B, Raghavendran HRB, Kamarul T
    Stem Cells Int, 2020;2020:5385960.
    PMID: 32908542 DOI: 10.1155/2020/5385960
    It has been suggested that mechanical strain may elicit cell differentiation in adult somatic cells through activation of epithelial sodium channels (ENaC). However, such phenomenon has not been previously demonstrated in mesenchymal stromal cells (MSCs). The present study was thus conducted to investigate the role of ENaC in human bone marrow-derived MSCs (hMSCs) tenogenic differentiation during uniaxial tensile loading. Passaged-2 hMSCs were seeded onto silicone chambers coated with collagen I and subjected to stretching at 1 Hz frequency and 8% strain for 6, 24, 48, and 72 hours. Analyses at these time points included cell morphology and alignment observation, immunocytochemistry and immunofluorescence staining (collagen I, collagen III, fibronectin, and N-cadherin), and gene expression (ENaC subunits, and tenogenic markers). Unstrained cells at similar time points served as the control group. To demonstrate the involvement of ENaC in the differentiation process, an ENaC blocker (benzamil) was used and the results were compared to the noninhibited hMSCs. ENaC subunits' (α, β, γ, and δ) expression was observed in hMSCs, although only α subunit was significantly increased during stretching. An increase in tenogenic genes' (collagen1, collagen3, decorin, tenascin-c, scleraxis, and tenomodulin) and proteins' (collagen I, collagen III, fibronectin, and N-cadherin) expression suggests that hMSCs underwent tenogenic differentiation when subjected to uniaxial loading. Inhibition of ENaC function resulted in decreased expression of these markers, thereby suggesting that ENaC plays a vital role in tenogenic differentiation of hMSCs during mechanical loading.
  15. Zeimaran E, Kadir MR, Nor HM, Kamarul T, Djordjevic I
    Bioorg Med Chem Lett, 2013 Dec 15;23(24):6616-9.
    PMID: 24215893 DOI: 10.1016/j.bmcl.2013.10.053
    In this study aliphatic polyacids were synthesized using palm acid oil (PAO) and sunflower oil (SFO) via addition reaction technique. The synthesized materials were characterized using Fourier-transform infra-red (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF-MS) and thermo-gravimetric analysis (TGA). Mixing formic acid and hydrogen peroxide with PAO or SFO at the ratio 3:10:1 produced the lowest iodine value of 10.57 and 9.24 respectively, indicating the increase in epoxidization of both oils. Adding adipic acid to the epoxidized oils at a ratio of 1:10 increases the acid values of SFO and PAO to 11.22 and 6.73 respectively. The existence of multi-acid groups present in synthesized polyacid was confirmed by MALD-ToF-MS. This feature indicates a possible value to the biomaterials development.
  16. Wee AS, Lim CK, Merican AM, Ahmad TS, Kamarul T
    In Vitro Cell Dev Biol Anim, 2013 Jun;49(6):424-32.
    PMID: 23708918 DOI: 10.1007/s11626-013-9626-0
    In vitro cellular proliferation and the ability to undergo multilineage differentiation make bone marrow-derived multipotent stromal cells (MSCs) potentially useful for clinical applications. Several methods have been described to isolate a homogenous bone marrow-derived MSCs population; however, none has been proven most effective, mainly due to their effects on proliferation and differentiation capability of the isolated cells. It is hypothesized that our newly established total cell pooling method may provide a better alternative as compared to the standard isolation method (density gradient centrifugation method). For the total cell pooling method, MSCs were isolated from rabbit bone marrow and were subsequently cultured in the growth medium without further separation as in the standard isolation method. The total cell pooling method was 65 min faster than the standard isolation method in completing cell isolation. Nevertheless, both methods did not differ significantly in the number of primary viable cells and population doubling time in the cultures (p > 0.05). The isolated cells from both methods expressed CD29 and CD44 markers, but not CD45 markers. Furthermore, they displayed multilineage differentiation characteristics of chondroblasts, osteoblasts, and adipocytes. In conclusion, both methods provide similar efficiency in the isolation of rabbit bone marrow-derived MSCs; however, the total cell pooling method is technically simpler and more cost effective than the standard isolation method.
  17. Choudhary R, Vecstaudza J, Krishnamurithy G, Raghavendran HRB, Murali MR, Kamarul T, et al.
    Mater Sci Eng C Mater Biol Appl, 2016 Nov 01;68:89-100.
    PMID: 27524000 DOI: 10.1016/j.msec.2016.04.110
    Diopside was synthesized from biowaste (Eggshell) by sol-gel combustion method at low calcination temperature and the influence of two different fuels (urea, l-alanine) on the phase formation temperature, physical and biological properties of the resultant diopside was studied. The synthesized materials were characterized by heating microscopy, FTIR, XRD, BET, SEM and EDAX techniques. BET analysis reveals particles were of submicron size with porosity in the nanometer range. Bone-like apatite deposition ability of diopside scaffolds was examined under static and circulation mode of SBF (Simulated Body Fluid). It was noticed that diopside has the capability to deposit HAP (hydroxyapatite) within the early stages of immersion. ICP-OES analysis indicates release of Ca, Mg, Si ions and removal of P ions from the SBF, but in different quantities from diopside scaffolds. Cytocompatability studies on human bone marrow stromal cells (hBMSCs) revealed good cellular attachment on the surface of diopside scaffolds and formation of extracellular matrix (ECM). This study suggests that the usage of eggshell biowaste as calcium source provides an effective substitute for synthetic starting materials to fabricate bioproducts for biomedical applications.
  18. Nam HY, Balaji Raghavendran HR, Pingguan-Murphy B, Abbas AA, Merican AM, Kamarul T
    PLoS One, 2017;12(6):e0178117.
    PMID: 28654695 DOI: 10.1371/journal.pone.0178117
    The role for mechanical stimulation in the control of cell fate has been previously proposed, suggesting that there may be a role of mechanical conditioning in directing mesenchymal stromal cells (MSCs) towards specific lineage for tissue engineering applications. Although previous studies have reported that calcium signalling is involved in regulating many cellular processes in many cell types, its role in managing cellular responses to tensile loading (mechanotransduction) of MSCs has not been fully elucidated. In order to establish this, we disrupted calcium signalling by blocking stretch-activated calcium channel (SACC) in human MSCs (hMSCs) in vitro. Passaged-2 hMSCs were exposed to cyclic tensile loading (1 Hz + 8% for 6, 24, 48, and 72 hours) in the presence of the SACC blocker, gadolinium. Analyses include image observations of immunochemistry and immunofluorescence staining from extracellular matrix (ECM) production, and measuring related tenogenic and apoptosis gene marker expression. Uniaxial tensile loading increased the expression of tenogenic markers and ECM production. However, exposure to strain in the presence of 20 μM gadolinium reduced the induction of almost all tenogenic markers and ECM staining, suggesting that SACC acts as a mechanosensor in strain-induced hMSC tenogenic differentiation process. Although cell death was observed in prolonged stretching, it did not appear to be apoptosis mediated. In conclusion, the knowledge gained in this study by elucidating the role of calcium in MSC mechanotransduction processes, and that in prolonged stretching results in non-apoptosis mediated cell death may be potential useful for regenerative medicine applications.
  19. Hiew MSY, Cheng HP, Huang CJ, Chong KY, Cheong SK, Choo KB, et al.
    J Biomed Sci, 2018 Jul 19;25(1):57.
    PMID: 30025541 DOI: 10.1186/s12929-018-0461-1
    BACKGROUND: Induced pluripotency in cancer cells by ectopic expression of pluripotency-regulating factors may be used for disease modeling of cancers. MicroRNAs (miRNAs) are negative regulators of gene expression that play important role in reprogramming somatic cells. However, studies on the miRNA expression profile and the expression patterns of the mesenchymal-epithelial transition (MET)/epithelial-mesenchymal transition (EMT) genes in induced pluripotent cancer (iPC) cells are lacking.

    METHODS: iPC clones were generated from two colorectal cancer (CRC) cell lines by retroviral transduction of the Yamanaka factors. The iPC clones obtained were characterized by morphology, expression of pluripotency markers and the ability to undergo in vitro tri-lineage differentiation. Genome-wide miRNA profiles of the iPC cells were obtained by microarray analysis and bioinformatics interrogation. Gene expression was done by real-time RT-PCR and immuno-staining; MET/EMT protein levels were determined by western blot analysis.

    RESULTS: The CRC-iPC cells showed embryonic stem cell-like features and tri-lineage differentiation abilities. The spontaneously-differentiated post-iPC cells obtained were highly similar to the parental CRC cells. However, down-regulated pluripotency gene expression and failure to form teratoma indicated that the CRC-iPC cells had only attained partial pluripotency. The CRC-iPC cells shared similarities in the genome-wide miRNA expression profiles of both cancer and pluripotent embryonic stem cells. One hundred and two differentially-expressed miRNAs were identified in the CRC-iPC cells, which were predicted by bioinformatics analysis be closely involved in regulating cellular pluripotency and the expression of the MET/EMT genes, possibly via the phosphatidylinositol-3 kinases-protein kinase B (PI3K-Akt) and transforming growth factor beta (TGF-β) signaling pathways. Irregular and inconsistent expression patterns of the EMT vimentin and Snai1 and MET E-cadherin and occludin proteins were observed in the four CRC-iPC clones analyzed, which suggested an epithelial/mesenchymal hybrid phenotype in the partially reprogrammed CRC cells. MET/EMT gene expression was also generally reversed on re-differentiation, also suggesting epigenetic regulation.

    CONCLUSIONS: Our data support the elite model for cancer cell-reprogramming in which only a selected subset of cancer may be fully reprogrammed; partial cancer cell reprogramming may also elicit an epithelial-mesenchymal mixed phenotype, and highlight opportunities and challenges in cancer cell-reprogramming.

  20. Larsson HM, Vythilingam G, Pinnagoda K, Vardar E, Engelhardt EM, Sothilingam S, et al.
    Sci Rep, 2018 07 03;8(1):10057.
    PMID: 29968749 DOI: 10.1038/s41598-018-27621-9
    There is a need for efficient and "off-the-shelf" grafts in urethral reconstructive surgery. Currently available surgical techniques require harvesting of grafts from autologous sites, with increased risk of surgical complications and added patient discomfort. Therefore, a cost-effective and cell-free graft with adequate regenerative potential has a great chance to be translated into clinical practice. Tubular cell-free collagen grafts were prepared by varying the collagen density and fiber distribution, thereby creating a polarized low fiber density collagen graft (LD-graft). A uniform, high fiber density collagen graft (HD-graft) was engineered as a control. These two grafts were implanted to bridge a 2 cm long iatrogenic urethral defect in a rabbit model. Histology revealed that rabbits implanted with the LD-graft had a better smooth muscle regeneration compared to the HD-graft. The overall functional outcome assessed by contrast voiding cystourethrography showed patency of the urethra in 90% for the LD-graft and in 66.6% for the HD-graft. Functional regeneration of the rabbit implanted with the LD-graft could further be demonstrated by successful mating, resulting in healthy offspring. In conclusion, cell-free low-density polarized collagen grafts show better urethral regeneration than high-density collagen grafts.
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