Displaying publications 1 - 20 of 33 in total

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  1. Rohaina CM, Then KY, Ng AM, Wan Abdul Halim WH, Zahidin AZ, Saim A, et al.
    Transl Res, 2014 Mar;163(3):200-10.
    PMID: 24286920 DOI: 10.1016/j.trsl.2013.11.004
    The cornea can be damaged by a variety of clinical disorders or chemical, mechanical, and thermal injuries. The objectives of this study were to induce bone marrow mesenchymal stem cells (BMSCs) to corneal lineage, to form a tissue engineered corneal substitute (TEC) using BMSCs, and to treat corneal surface defects in a limbal stem cell deficiency model. BMSCs were induced to corneal lineage using limbal medium for 10 days. Induced BMSCs demonstrated upregulation of corneal stem cell markers; β1-integrin, C/EBPδ, ABCG2, and p63, increased protein expression of CK3 and p63 significantly compared with the uninduced ones. For TEC formation, passage 1 BMSCs were trypsinized and seeded on amniotic membrane in a transwell co-culture system and were grown in limbal medium. Limbal stem cell deficiency models were induced by alkaline injury, and the TEC was implanted for 8 weeks. Serial slit lamp evaluation revealed remarkable improvement in corneal regeneration in terms of corneal clarity and reduced vascularization. Histologic and optical coherence tomography analyses demonstrated comparable corneal thickness and achieved stratified epithelium with a compact stromal layer resembling that of normal cornea. CK3 and p63 were expressed in the newly regenerated cornea. In conclusion, BMSCs can be induced into corneal epithelial lineage, and these cells are viable for the formation of TEC, to be used for the reconstruction of the corneal surface in the limbal stem cell deficient model.
  2. Chowdhury SR, binti Ismail A, Chee SC, bin Laupa MS, binti Jaffri F, Saberi SE, et al.
    Tissue Eng Part C Methods, 2015 Nov;21(11):1135-42.
    PMID: 26061720 DOI: 10.1089/ten.TEC.2015.0015
    Skeletal myoblasts have been extensively used to study muscle growth and differentiation, and were recently tested for their application as cell therapy and as a gene delivery system to treat muscle and nonmuscle diseases. However, contamination of fibroblasts in isolated cells from skeletal muscle is one of the long-standing problems for routine expansion. This study aimed to establish a simple one-step process to purify myoblasts and maintain their purity during expansion. Mixed cells were preplated serially on laminin- and collagen type I-coated surfaces in a different array for 5, 10, and 15 min. Immunocytochemical staining with antibodies specific to myoblasts was performed to evaluate myoblast attachment efficiency, purity, and yield. It was found that laminin-coated surface favors the attachment of myoblasts. Highest myoblast purity of 78.9% ± 6.8% was achieved by 5 min of preplating only on the laminin-coated surface with a yield of 56.9% ± 3.3%. Primary cells, isolated from skeletal muscle (n = 4), confirm the enhancement of purity through preplating on laminin-coated surface for 5 min. Subsequent expansion after preplating enhanced myoblast purity due to an increase in myoblast growth than fibroblasts. Myoblast purity of ∼ 98% was achieved when another preplating was performed during passaging. In conclusion, myoblasts can be purified and efficiently expanded in one step by preplating on laminin-coated surface, which is a simple and robust technique.
  3. Hasmad H, Yusof MR, Mohd Razi ZR, Hj Idrus RB, Chowdhury SR
    Tissue Eng Part C Methods, 2018 06;24(6):368-378.
    PMID: 29690856 DOI: 10.1089/ten.TEC.2017.0447
    Fabrication of composite scaffolds is one of the strategies proposed to enhance the functionality of tissue-engineered scaffolds for improved tissue regeneration. By combining multiple elements together, unique biomimetic scaffolds with desirable physical and mechanical properties can be tailored for tissue-specific applications. Despite having a highly porous structure, the utility of electrospun fibers (EF) as scaffold is usually hampered by their insufficient mechanical strength. In this study, we attempted to produce a mechanically competent scaffold with cell-guiding ability by fabricating aligned poly lactic-co-glycolic acid (PLGA) fibers on decellularized human amniotic membrane (HAM), known to possess favorable tensile and wound healing properties. Decellularization of HAM in 18.75 μg/mL of thermolysin followed by a brief treatment in 0.25 M sodium hydroxide efficiently removed the amniotic epithelium and preserved the ultrastructure of the underlying extracellular matrix. The electrospinning of 20% (w/v) PLGA 50:50 polymer on HAM yielded beadless fibers with straight morphology. Subsequent physical characterization revealed that EF-HAM scaffold with a 3-min fabrication had the most aligned fibers with the lowest fiber diameter in comparison with EF-HAM 5- and 7-min scaffolds. Hydrated EF-HAM scaffolds with 3-min deposition had a greater tensile strength than the other scaffolds despite having thinner fibers. Nevertheless, wet HAM and EF-HAMs regardless of the fiber thicknesses had a significantly lower Young's modulus, and hence, a higher elasticity compared with dry HAM and EF-HAMs. Biocompatibility analysis showed that the viability and migration rate of skeletal muscle cells on EF-HAMs were similar to control and HAM alone. Skeletal muscle cells seeded on HAM were shown to display random orientation, whereas cells on EF-HAM scaffolds were oriented along the alignment of the electrospun PLGA fibers. In summary, besides having good mechanical strength and elasticity, EF-HAM scaffold design decorated with aligned fiber topography holds a promising potential for use in the development of aligned tissue constructs.
  4. Salem SA, Rashidbenam Z, Jasman MH, Ho CCK, Sagap I, Singh R, et al.
    Tissue Eng Regen Med, 2020 08;17(4):553-563.
    PMID: 32583275 DOI: 10.1007/s13770-020-00271-7
    BACKGROUND: The urinary tract can be affected by both congenital abnormalities as well as acquired disorders, such as cancer, trauma, infection, inflammation, and iatrogenic injuries, all of which may lead to organ damage requiring eventual reconstruction. As a gold standard, gastrointestinal segment is used for urinary bladder reconstruction. However, one major problem is that while bladder tissue prevents reabsorption of specific solutes, gastrointestinal tissue actually absorbs them. Therefore, tissue engineering approach had been attempted to provide an alternative tissue graft for urinary bladder reconstruction.

    METHODS: Human adipose-derived stem cells isolated from fat tissues were differentiated into smooth muscle cells and then seeded onto a triple-layered PLGA sheet to form a bladder construct. Adult athymic rats underwent subtotal urinary bladder resection and were divided into three treatment groups (n = 3): Group 1 ("sham") underwent anastomosis of the remaining basal region, Group 2 underwent reconstruction with the cell-free scaffold, and Group 3 underwent reconstruction with the tissue-engineered bladder construct. Animals were monitored on a daily basis and euthanisation was performed whenever a decline in animal health was detected.

    RESULTS: All animals in Groups 1, 2 and 3 survived for at least 7 days and were followed up to a maximum of 12 weeks post-operation. It was found that by Day 14, substantial ingrowth of smooth muscle and urothelial cells had occurred in Group 2 and 3. In the long-term follow up of group 3 (tissue-engineered bladder construct group), it was found that the urinary bladder wall was completely regenerated and bladder function was fully restored. Urodynamic and radiological evaluations of the reconstructed bladder showed a return to normal bladder volume and function.Histological analysis revealed the presence of three muscular layers and a urothelium similar to that of a normal bladder. Immunohistochemical staining using human-specific myocyte markers (myosin heavy chain and smoothelin) confirmed the incorporation of the seeded cells in the newly regenerated muscular layers.

    CONCLUSION: Implantation of PLGA construct seeded with smooth muscle cells derived from human adipose stem cells can lead to regeneration of the muscular layers and urothelial ingrowth, leading to formation of a completely functional urinary bladder.

  5. Yunus MH, Siang KC, Hashim NI, Zhi NP, Zamani NF, Sabri PP, et al.
    Tissue Cell, 2014 Aug;46(4):233-40.
    PMID: 24973262 DOI: 10.1016/j.tice.2014.05.003
    The culture of human airway epithelial cells has played an important role in advancing our understanding of the metabolic and molecular mechanisms underlying normal function and disease pathology of airway epithelial cells. The present study focused on investigating the effects of human serum (HS) on the qualitative and quantitative properties of the human respiratory epithelium compared to the fetal bovine serum (FBS), as a supplement in culture. Respiratory epithelial (RE) cells derived from human nasal turbinate were co-cultured with fibroblasts, subsequently separated at 80-90% confluency by differential trypsinization. RE cells were then sub-cultured into 2 different plates containing 5% allogenic HS and FBS supplemented media respectively up to passage 1 (P1). Cell morphology, growth rate, cell viability and population doubling time were assessed under light microscope, and levels of gene expression were measured via real time reverse transcriptase-polymerase chain reaction (qRT-PCR). RE cells appeared as polygonal shape and expanded when cultured in HS whereas RE cells in FBS were observed to be easily matured thus limit the RE cells expansion. Proliferation rate of RE cells in HS supplemented media (7673.18 ± 1207.15) was 3 times higher compared to RE in FBS supplemented media (2357.68 ± 186.85). Furthermore, RE cells cultured in HS-supplemented media required fewer days (9.15 ± 1.10) to double in numbers compared to cells cultured in FBS-supplemented media (13.66 ± 0.81). Both the differences were significant (p<0.05). However, there were no significant differences in the viability of RE cells in both groups (p=0.105). qRT-PCR showed comparable expressions of gene Cytokeratin-14 (CK-14), Cytokeratin-18 (CK-18) and Mucin-5 subtype B (MUC5B) in RE cells cultured in both groups (p>0.05). In conclusion, HS is a comparatively better choice of media supplement in accelerating growth kinetics of RE cells in vitro thus producing a better quality of respiratory epithelium for future tracheal reconstruction.
  6. Ubaidah MA, Chua KH, Ami M, Zainal A, Saim A, Saim L, et al.
    J Int Adv Otol, 2015 Apr;11(1):23-9.
    PMID: 26223713 DOI: 10.5152/iao.2015.539
    Loss of auditory hair cells is a major cause of deafness. The presence of auditory progenitor cells in the inner ear raises the hope for mammalian inner ear cell regeneration. In this study, we aimed to investigate the effect of growth factor supplementations, namely a combination of epidermal growth factor (EGF), insulin-like growth factor (IGF), and beta (β)-fibroblast growth factor (βFGF), on the expression of hair cell-specific markers by cells harvested from the cochlear membrane. This would provide an insight into the capability of these cells to differentiate into hair cells.
  7. Sulaiman SB, Keong TK, Cheng CH, Saim AB, Idrus RB
    Indian J Med Res, 2013 Jun;137(6):1093-101.
    PMID: 23852290
    Various materials have been used as scaffolds to suit different demands in tissue engineering. One of the most important criteria is that the scaffold must be biocompatible. This study was carried out to investigate the potential of HA or TCP/HA scaffold seeded with osteogenic induced sheep marrow cells (SMCs) for bone tissue engineering.
  8. Idrus RB, Mohamad NB, Morat PB, Saim A, Abdul Kadir KB
    Steroids, 1996 Aug;61(8):448-52.
    PMID: 8870163
    11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) is a microsomal enzyme that catalyzes the dehydrogenation of cortisol (F) to cortisone (E) in man and corticosterone (B) to 11-dehydrocorticosterone (A) in rats. 11 beta-OHSD has been identified in a wide variety of tissues. The differential distribution of 11 beta-OHSD suggests that this enzyme has locally defined functions that vary from region to region. The aim of this study was to investigate the effects of the glucocorticoids B and dexamethasone (DM), the mineralocorticoid deoxycorticosterone (DOC), and the inhibitors of 11 beta-OHSD glycyrrhizic acid (Gl) and glycyrrhetinic acid (GE) on 11 beta-OHSD bioactivity at the hypothalamus (HT) and anterior pituitary (AP). Male Wistar rats were treated with GI or were adrenalectomized (ADX) and treated with either B, DM, or DOC for 7 days. All treatments were in vivo except GE, which was used in vitro. At the end of treatment, homogenates of HT and AP were assayed for 11 beta-OHSD bioactivity, expressed as the percentage conversion of B to A in the presence of NADP, 11 beta-OHSD bioactivity is significantly higher (P < 0.0001) in the AP compared with the HT. Adrenalectomy significantly increased the enzyme activity in the AP (P < 0.05), an effect reversed by B or DM. ADX rats treated with DOC showed decreased enzyme activity in the AP (P < 0.001) but increased the activity in the HT (P < 0.0001). Gl increased activity in both HT and AP, whereas GE decreased activity significantly. We conclude that the modulation of 11 beta-OHSD is both steroid specific and tissue specific.
  9. Busra FM, Chowdhury SR, Saim AB, Idrus RB
    Saudi Med J, 2011 Dec;32(12):1311-2.
    PMID: 22159390
  10. Ude CC, Sulaiman SB, Min-Hwei N, Hui-Cheng C, Ahmad J, Yahaya NM, et al.
    PLoS One, 2014;9(6):e98770.
    PMID: 24911365 DOI: 10.1371/journal.pone.0098770
    In this study, Adipose stem cells (ADSC) and bone marrow stem cells (BMSC), multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model.
  11. Ude CC, Ng MH, Chen CH, Htwe O, Amaramalar NS, Hassan S, et al.
    Osteoarthritis Cartilage, 2015 Aug;23(8):1294-306.
    PMID: 25887366 DOI: 10.1016/j.joca.2015.04.003
    OBJECTIVES: Our previous studies on osteoarthritis (OA) revealed positive outcome after chondrogenically induced cells treatment. Presently, the functional improvements of these treated OA knee joints were quantified followed by evaluation of the mechanical properties of the engineered cartilages.
    METHODS: Baseline electromyogram (EMGs) were conducted at week 0 (pre-OA), on the locomotory muscles of nine un-castrated male sheep (Siamese long tail cross) divided into controls, adipose-derived stem cells (ADSCs) and bone marrow stem cells (BMSCs), before OA inductions. Subsequent recordings were performed at week 7 and week 31 which were post-OA and post-treatments. Afterwards, the compression tests of the regenerated cartilage were performed.
    RESULTS: Post-treatment EMG analysis revealed that the control sheep retained significant reductions in amplitudes at the right medial gluteus, vastus lateralis and bicep femoris, whereas BMSCs and ADSCs samples had no further significant reductions (P < 0.05). Grossly and histologically, the treated knee joints demonstrated the presence of regenerated neo cartilages evidenced by the fluorescence of PKH26 tracker. Based on the International Cartilage Repair Society scores (ICRS), they had significantly lower grades than the controls (P < 0.05). The compression moduli of the native cartilages and the engineered cartilages differed significantly at the tibia plateau, patella femoral groove and the patella; whereas at the medial femoral condyle, they had similar moduli of 0.69 MPa and 0.40-0.64 MPa respectively. Their compression strengths at all four regions were within ±10 MPa.
    CONCLUSION: The tissue engineered cartilages provided evidence of functional recoveries associated to the structural regenerations, and their mechanical properties were comparable with the native cartilage.
    KEYWORDS: Cartilage; Cell therapy; Function; Osteoarthritis; Regeneration
  12. Ng AM, Saim AB, Tan KK, Tan GH, Mokhtar SA, Rose IM, et al.
    J Orthop Sci, 2005;10(2):192-9.
    PMID: 15815868
    Osteoprogenitor cells have been reported to be present in periosteum, cancellous and cortical bone, and bone marrow; but no attempt to identify the best cell source for bone tissue engineering has yet been reported. In this study, we aimed to investigate the growth and differentiation pattern of cells derived from these four sources in terms of cell doubling time and expression of osteoblast-specific markers in both monolayer cells and three-dimensional cell constructs in vitro. In parallel, human plasma derived-fibrin was evaluated for use as biomaterial when forming three-dimensional bone constructs. Our findings showed osteoprogenitor cells derived from periosteum to be most proliferative followed by cortical bone, cancellous bone, and then bone marrow aspirate. Bone-forming activity was observed in constructs formed with cells derived from periosteum, whereas calcium deposition was seen throughout the constructs formed with cells derived from cancellous and cortical bones. Although no mineralization activity was seen in constructs formed with osteoprogenitor cells derived from bone marrow, well-organized lacunae as would appear in the early phase of bone reconstruction were noted. Scanning electron microscopy evaluation showed cell proliferation throughout the fibrin matrix, suggesting the possible application of human fibrin as the bioengineered tissue scaffold at non-load-bearing sites.
  13. Hassan NH, Sulong AF, Ng MH, Htwe O, Idrus RB, Roohi S, et al.
    J Orthop Res, 2012 Oct;30(10):1674-81.
    PMID: 22411691 DOI: 10.1002/jor.22102
    Autologous nerve grafts to bridge nerve gaps have donor site morbidity and possible neuroma formation resulting in development of various methods of bridging nerve gaps without using autologous nerve grafts. We have fabricated an acellular muscle stuffed vein seeded with differentiated mesenchymal stem cells (MSCs) as a substitute for nerve autografts. Human vein and muscle were both decellularized by liquid nitrogen immersion with subsequent hydrolysis in hydrochloric acid. Human MSCs were subjected to a series of treatments with a reducing agent, retinoic acid, and a combination of trophic factors. The differentiated MSCs were seeded on the surface of acellular muscle tissue and then stuffed into the vein. Our study showed that 35-75% of the cells expressed neural markers such as S100b, glial fibrillary acidic protein (GFAP), p75 NGF receptor, and Nestin after differentiation. Histological and ultra structural analyses of muscle stuffed veins showed attachment of cells onto the surface of the acellular muscle and penetration of the cells into the hydrolyzed fraction of muscle fibers. We implanted these muscle stuffed veins into athymic mice and at 8 weeks post-implantation, the acellular muscle tissue had fully degraded and replaced with new matrix produced by the seeded cells. The vein was still intact and no inflammatory reactions were observed proving the biocompatibility and biodegradability of the conduit. In conclusion, we have successfully formed a stable living nerve conduit which may serve as a substitute for autologous nerves.
  14. Salem SA, Hwei NM, Bin Saim A, Ho CC, Sagap I, Singh R, et al.
    J Biomed Mater Res A, 2013 Aug;101(8):2237-47.
    PMID: 23349110 DOI: 10.1002/jbm.a.34518
    The chief obstacle for reconstructing the bladder is the absence of a biomaterial, either permanent or biodegradable, that will function as a suitable scaffold for the natural process of regeneration. In this study, polylactic-co-glycolic acid (PLGA) plus collagen or fibrin was evaluated for its suitability as a scaffold for urinary bladder construct. Human adipose-derived stem cells (HADSCs) were cultured, followed by incubation in smooth muscle cells differentiation media. Differentiated HADSCs were then seeded onto PLGA mesh supported with collagen or fibrin. Evaluation of cell-seeded PLGA composite immersed in culture medium was performed under a light and scanning microscope. To determine if the composite is compatible with the urodynamic properties of urinary bladder, porosity and leaking test was performed. The PLGA samples were subjected to tensile testing was pulled until PLGA fibers break. The results showed that the PLGA composite is biocompatible to differentiated HADSCs. PLGA-collagen mesh appeared to be optimal as a cell carrier while the three-layered PLGA-fibrin composite is better in relation to its leaking/ porosity property. A biomechanical test was also performed for three-layered PLGA with biological adhesive and three-layered PLGA alone. The tensile stress at failure was 30.82 ± 3.80 (MPa) and 34.36 ± 2.57 (MPa), respectively. Maximum tensile strain at failure was 19.42 ± 2.24 (mm) and 23.06 ± 2.47 (mm), respectively. Young's modulus was 0.035 ± 0.0083 and 0.043 ± 0.012, respectively. The maximum load at break was 58.55 ± 7.90 (N) and 65.29 ± 4.89 (N), respectively. In conclusion, PLGA-Fibrin fulfils the criteria as a scaffold for urinary bladder reconstruction.
  15. Sha'ban M, Yoon SJ, Ko YK, Ha HJ, Kim SH, So JW, et al.
    J Biomater Sci Polym Ed, 2008;19(9):1219-37.
    PMID: 18727862 DOI: 10.1163/156856208785540163
    Previously, we have proven that fibrin and poly(lactic-co-glycolic acid) (PLGA) scaffolds facilitate cell proliferation, matrix production and early chondrogenesis of rabbit articular chondrocytes in in vitro and in vivo experiments. In this study, we evaluated the potential of fibrin/PLGA scaffold for intervertebral disc (IVD) tissue engineering using annulus fibrosus (AF) and nucleus pulposus (NP) cells in relation to potential clinical application. PLGA scaffolds were soaked in cells-fibrin suspension and polymerized by dropping thrombin-sodium chloride (CaCl(2)) solution. A PLGA-cell complex without fibrin was used as control. Higher cellular proliferation activity was observed in fibrin/PLGA-seeded AF and NP cells at each time point of 3, 7, 14 and 7 days using the MTT assay. After 3 weeks in vitro incubation, fibrin/PLGA exhibited a firmer gross morphology than PLGA groups. A significant cartilaginous tissue formation was observed in fibrin/PLGA, as proven by the development of cells cluster of various sizes and three-dimensional (3D) cartilaginous histoarchitecture and the presence of proteoglycan-rich matrix and glycosaminoglycan (GAG). The sGAG production measured by 1,9-dimethylmethylene blue (DMMB) assay revealed greater sGAG production in fibrin/PLGA than PLGA group. Immunohistochemical analyses showed expressions of collagen type II, aggrecan core protein and collagen type I genes throughout in vitro culture in both fibrin/PLGA and PLGA. In conclusion, fibrin promotes cell proliferation, stable in vitro tissue morphology, superior cartilaginous tissue formation and sGAG production of AF and NP cells cultured in PLGA scaffold. The 3D porous PLGA scaffold-cell complexes using fibrin can provide a vehicle for delivery of cells to regenerate tissue-engineered IVD tissue.
  16. Ishak MF, See GB, Hui CK, Abdullah Ab, Saim Lb, Saim Ab, et al.
    Int J Pediatr Otorhinolaryngol, 2015 Oct;79(10):1634-9.
    PMID: 26250439 DOI: 10.1016/j.ijporl.2015.06.034
    This study aimed to isolate, culture-expand and characterize the chondrocytes isolated from microtic cartilage and evaluate its potential as a cell source for ear cartilage reconstruction. Specific attention was to construct the auricular cartilage tissue by using fibrin as scaffold.
  17. Mok PL, Leow SN, Koh AE, Mohd Nizam HH, Ding SL, Luu C, et al.
    Int J Mol Sci, 2017 Feb 08;18(2).
    PMID: 28208719 DOI: 10.3390/ijms18020345
    Mesenchymal stem cells are widely used in many pre-clinical and clinical settings. Despite advances in molecular technology; the migration and homing activities of these cells in in vivo systems are not well understood. Labelling mesenchymal stem cells with gold nanoparticles has no cytotoxic effect and may offer suitable indications for stem cell tracking. Here, we report a simple protocol to label mesenchymal stem cells using 80 nm gold nanoparticles. Once the cells and particles were incubated together for 24 h, the labelled products were injected into the rat subretinal layer. Micro-computed tomography was then conducted on the 15th and 30th day post-injection to track the movement of these cells, as visualized by an area of hyperdensity from the coronal section images of the rat head. In addition, we confirmed the cellular uptake of the gold nanoparticles by the mesenchymal stem cells using transmission electron microscopy. As opposed to other methods, the current protocol provides a simple, less labour-intensive and more efficient labelling mechanism for real-time cell tracking. Finally, we discuss the potential manipulations of gold nanoparticles in stem cells for cell replacement and cancer therapy in ocular disorders or diseases.
  18. Razali RA, Lokanathan Y, Yazid MD, Ansari AS, Saim AB, Hj Idrus RB
    Int J Mol Sci, 2019 Jul 16;20(14).
    PMID: 31315241 DOI: 10.3390/ijms20143492
    Epithelial-mesenchymal transition (EMT) is a significant dynamic process that causes changes in the phenotype of epithelial cells, changing them from their original phenotype to the mesenchymal cell phenotype. This event can be observed during wound healing process, fibrosis and cancer. EMT-related diseases are usually caused by inflammation that eventually leads to tissue remodeling in the damaged tissue. Prolonged inflammation causes long-term EMT activation that can lead to tissue fibrosis or cancer. Due to activation of EMT by its signaling pathway, therapeutic approaches that modulate that pathway should be explored. Olea europaea (OE) is well-known for its anti-inflammatory effects and abundant beneficial active compounds. These properties are presumed to modulate EMT events. This article reviews recent evidence of the effects of OE and its active compounds on EMT events and EMT-related diseases. Following evidence from the literature, it was shown that OE could modulate TGFβ/SMAD, AKT, ERK, and Wnt/β-catenin pathways in EMT due to a potent active compound that is present therein.
  19. Vijakumaran U, Yazid MD, Hj Idrus RB, Abdul Rahman MR, Sulaiman N
    Front Pharmacol, 2021;12:663266.
    PMID: 34093194 DOI: 10.3389/fphar.2021.663266
    Objective: Hydroxytyrosol (HT), a polyphenol of olive plant is well known for its antioxidant, anti-inflammatory and anti-atherogenic properties. The aim of this systematic search is to highlight the scientific evidence evaluating molecular efficiency of HT in halting the progression of intimal hyperplasia (IH), which is a clinical condition arises from endothelial inflammation. Methods: A systematic search was performed through PubMed, Web of Science and Scopus, based on pre-set keywords which are Hydroxytyrosol OR 3,4-dihydroxyphenylethanol, AND Intimal hyperplasia OR Neointimal hyperplasia OR Endothelial OR Smooth muscles. Eighteen in vitro and three in vitro and in vivo studies were selected based on a pre-set inclusion and exclusion criteria. Results: Based on evidence gathered, HT was found to upregulate PI3K/AKT/mTOR pathways and supresses inflammatory factors and mediators such as IL-1β, IL-6, E-selectin, P-selectin, VCAM-1, and ICAM-1 in endothelial vascularization and functioning. Two studies revealed HT disrupted vascular smooth muscle cells (SMC) cell cycle by dephosphorylating ERK1/2 and AKT pathways. Therefore, HT was proven to promote endothelization and inhibit vascular SMCs migration thus hampering IH development. However, none of these studies described the effect of HT collectively in both vascular endothelial cells (EC) and SMCs in IH ex vivo model. Conclusions: Evidence from this concise review provides an insight on HT regulation of molecular pathways in reendothelization and inhibition of VSMCs migration. Henceforth, we propose effect of HT on IH prevention could be further elucidated through in vivo and ex vivo model.
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