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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.
Fulltext Free radial forearm flap after partial glossectomy for squamous cell carcinoma of the tongue

Chuah, U.C., Kamarul, T., Sara, T.

JUMMEC, 2006;9(2):28-31.
MyJurnal

Squamous cell carcinoma of the tongue is a highly malignant condition and results in high mortality and morbidity in patients despite its early detection (1). Early surgical interventions have been found to reduce mortality but in many reports, tongue reconstructions using live grafts have been found to reduce normal tongue function of speech, swallow and taste. In contrast, our report using free radial forearm flap (FRFF) to reconstruct the defect left over after a radical tongue resection in a 38-year-old gentleman with oral cancer has shown promising results. This type of reconstruction has left the patient with a functional and cosmetically acceptable tongue with minimal alteration in recognizable speech.
Fulltext Fluoroscopy assisted minimally invasive transplantation of allogenic mesenchymal stromal cells embedded in HyStem reduces the progression of nucleus pulposus degeneration in the damaged ntervertebral [corrected] disc: a preliminary study in rabbits

Subhan RA, Puvanan K, Murali MR, Raghavendran HR, Shani S, Abdullah BJ, et al.

ScientificWorldJournal, 2014;2014:818502.
PMID: 24983002 DOI: 10.1155/2014/818502

This study was conducted to develop a technique for minimally invasive and accurate delivery of stem cells to augment nucleus pulposus (NP) in damaged intervertebral discs (IVD). IVD damage was created in noncontiguous discs at L4-L5 level; rabbits (N = 12) were randomly divided into three groups: group I treated with MSCs in HyStem hydrogel, group II treated with HyStem alone, and group III received no intervention. MSCs and hydrogel were administered to the damaged disc under guidance of fluoroscopy. Augmentation of NP was assessed through histological and MRI T2 mapping of the NP after eight weeks of transplantation. T2 weighted signal intensity was higher in group I than in groups II and III (P < 0.05). Disc height index showed maximum disc height in group I compared to groups II and III. Histological score of the degenerative index was significantly (P < 0.05) lower in group I (8.6 ± 1.8) than that in groups II (11.6 ± 2.3) and III (18.0 ± 5.7). Immunohistochemistry staining for collagen type II and aggrecan staining were higher in group I as compared to other groups. Our results demonstrate that the minimally invasive administration of MSCs in hyaluronan hydrogel (HyStem) augments the repair of NP in damaged IVD.
Fulltext Flavokawain derivative FLS induced G2/M arrest and apoptosis on breast cancer MCF-7 cell line

Ali NM, Akhtar MN, Ky H, Lim KL, Abu N, Zareen S, et al.

Drug Des Devel Ther, 2016;10:1897-907.
PMID: 27358555 DOI: 10.2147/DDDT.S102164

Known as naturally occurring biologically active compounds, flavokawain A and B are the leading chalcones that possess anticancer properties. Another flavokawain derivative, (E)-1-(2'-Hydroxy-4',6'-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS) was characterized with (1)H-nuclear magnetic resonance, electron-impact mas spectrometry, infrared spectroscopy, and ultraviolet ((1)H NMR, EI-MS, IR, and UV) spectroscopic techniques. FLS cytotoxic efficacy against human cancer cells (MCF-7, MDA-MB-231, and MCF-10A) resulted in the reduction of IC50 values in a time- and dose-dependent mode with high specificity on MCF-7 (IC50 of 36 μM at 48 hours) against normal breast cell MCF-10A (no IC50 detected up to 180 μM at 72 hours). Light, scanning electron, and fluorescent microscopic analysis of MCF-7 cells treated with 36 μM of FLS displayed cell shrinkage, apoptotic body, and DNA fragmentation. Additionally, induction of G2/M cell arrest within 24 hours and apoptosis at subsequent time points was discovered via flow cytometry analysis. The roles of PLK-1, Wee-1, and phosphorylation of CDC-2 in G2/M arrest and proapoptotic factors (Bax, caspase 9, and p53) in promotion of apoptosis of FLS against MCF-7 cells were discovered using fluorometric, quantitative real-time polymerase chain reaction, and Western blot analysis. Interestingly, the presence of SCH3 (thiomethyl group) on ring B structure contributed to the selective cytotoxicity against MCF-7 cells compared to other chalcones, flavokawain A and B. Overall, our data suggest potential therapeutic value for flavokawain derivative FLS to be further developed as a new anticancer drug.
Finite element analysis of three commonly used external fixation devices for treating Type III pilon fractures

Ramlee MH, Kadir MR, Murali MR, Kamarul T

Med Eng Phys, 2014 Oct;36(10):1322-30.
PMID: 25127377 DOI: 10.1016/j.medengphy.2014.05.015

Pilon fractures are commonly caused by high energy trauma and can result in long-term immobilization of patients. The use of an external fixator i.e. the (1) Delta, (2) Mitkovic or (3) Unilateral frame for treating type III pilon fractures is generally recommended by many experts owing to the stability provided by these constructs. This allows this type of fracture to heal quickly whilst permitting early mobilization. However, the stability of one fixator over the other has not been previously demonstrated. This study was conducted to determine the biomechanical stability of these external fixators in type III pilon fractures using finite element modelling. Three-dimensional models of the tibia, fibula, talus, calcaneus, navicular, cuboid, three cuneiforms and five metatarsal bones were reconstructed from previously obtained CT datasets. Bones were assigned with isotropic material properties, while the cartilage was assigned as hyperelastic springs with Mooney-Rivlin properties. Axial loads of 350 N and 70 N were applied at the tibia to simulate the stance and the swing phase of a gait cycle. To prevent rigid body motion, the calcaneus and metatarsals were fixed distally in all degrees of freedom. The results indicate that the model with the Delta frame produced the lowest relative micromovement (0.03 mm) compared to the Mitkovic (0.05 mm) and Unilateral (0.42 mm) fixators during the stance phase. The highest stress concentrations were found at the pin of the Unilateral external fixator (509.2 MPa) compared to the Mitkovic (286.0 MPa) and the Delta (266.7 MPa) frames. In conclusion, the Delta external fixator was found to be the most stable external fixator for treating type III pilon fractures.
Finite element analysis of Puddu and Tomofix plate fixation for open wedge high tibial osteotomy

Raja Izaham RM, Abdul Kadir MR, Abdul Rashid AH, Hossain MG, Kamarul T

Injury, 2012 Jun;43(6):898-902.
PMID: 22204773 DOI: 10.1016/j.injury.2011.12.006

The use of open wedge high tibial osteotomy (HTO) to correct varus deformity of the knee is well established. However, the stability of the various implants used in this procedure has not been previously demonstrated. In this study, the two most common types of plates were analysed (1) the Puddu plates that use the dynamic compression plate (DCP) concept, and (2) the Tomofix plate that uses the locking compression plate (LCP) concept. Three dimensional model of the tibia was reconstructed from computed tomography images obtained from the Medical Implant Technology Group datasets. Osteotomy and fixation models were simulated through computational processing. Simulated loading was applied at 60:40 ratios on the medial:lateral aspect during single limb stance. The model was fixed distally in all degrees of freedom. Simulated data generated from the micromotions, displacement and, implant stress were captured. At the prescribed loads, a higher displacement of 3.25 mm was observed for the Puddu plate model (p<0.001). Coincidentally the amount of stresses subjected to this plate, 24.7 MPa, was also significantly lower (p<0.001). There was significant negative correlation (p<0.001) between implant stresses to that of the amount of fracture displacement which signifies a less stable fixation using Puddu plates. In conclusion, this study demonstrates that the Tomofix plate produces superior stability for bony fixation in HTO procedures.
Fulltext Fiber density of collagen grafts impacts rabbit urethral regeneration

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.
Fulltext Fate of tenogenic differentiation potential of human bone marrow stromal cells by uniaxial stretching affected by stretch-activated calcium channel agonist gadolinium

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.
Fulltext Factors Influencing the Successful Isolation and Expansion of Aging Human Mesenchymal Stem Cells

Chong PP, Selvaratnam L, Abbas AA, Kamarul T

Open Life Sci, 2018 Jan;13:279-284.
PMID: 33817094 DOI: 10.1515/biol-2018-0034

Most studies highlight mesenchymal stem cells (MSCs) extracted primarily from bone marrow (BM), very few report the use of peripheral blood (PB), often due to the associated low seeding density and difficulties with extraction techniques. As ageing populations are becoming more predominant globally, together with escalating demands for MSC transplantation and tissue regeneration, obtaining quality MSCs suitable for induced differentiation and biological therapies becomes increasingly important. In this study, BM and PB were obtained from elderly patients and extracted MSCs grown in vitro to determine their successful isolation and expansion. Patients' socio-demographic background and other medical information were obtained from medical records. Successful and failed cultures were correlated with key demographic and medical parameters. A total of 112 samples (BM or PB) were used for this study. Of these, 50 samples (44.6%) were successfully cultured according to standardised criteria with no signs of contamination. Our comparative analyses demonstrated no statistical correlation between successful MSC cultures and any of the six demographic or medical parameters examined, including sample quantity, age, sex, race, habits and underlying comorbidities of sample donors. In conclusion, the present study demonstrates that typical demographics and comorbidities do not influence successful MSC isolation and expansion in culture.
Fabrication and in vitro biological activity of βTCP-Chitosan-Fucoidan composite for bone tissue engineering

Puvaneswary S, Talebian S, Raghavendran HB, Murali MR, Mehrali M, Afifi AM, et al.

Carbohydr Polym, 2015 Dec 10;134:799-807.
PMID: 26428187 DOI: 10.1016/j.carbpol.2015.07.098

We developed tricalcium phosphate-chitosan-fucoidan biocomposite scaffold (TCP-Ch-Fu) by using the freeze-drying technique. The fabricated biocomposite scaffolds were analyzed by spectroscopy and porosity measurement. The biomechanical properties of scaffolds were assessed by compression test and the results suggested that the incorporation of Fucoidan into the biocomposite improves the compression strength of scaffolds. Biomineralization of scaffolds was evaluated by soaking them in simulated body fluid and the results revealed that the addition of Fucoidan into the scaffolds enhanced the formation of apatite layer on the surface of biocomposite after 7 days of immersion. Alamar Blue assay confirmed that the cell viability of human-derived bone marrow stromal cell was superior in the TCP-Ch-Fuscaffold. The addition of Fucoidan to TCP-Ch increased the release of osteocalcin, confirming that it can support osteogenic differentiation of human mesenchymal stromal cells in in vitro culture. Thus, TCP-Ch-Fu could be a potential candidate for bone-tissue engineering applications.
Expansion and preservation of multipotentiality of rabbit bone-marrow derived mesenchymal stem cells in dextran-based microcarrier spin culture

Boo L, Selvaratnam L, Tai CC, Ahmad TS, Kamarul T

J Mater Sci Mater Med, 2011 May;22(5):1343-56.
PMID: 21461701 DOI: 10.1007/s10856-011-4294-7

The use of mesenchymal stem cells (MSCs) in tissue repair and regeneration despite their multipotentiality has been limited by their cell source quantity and decelerating proliferative yield efficiency. A study was thus undertaken to determine the feasibility of using microcarrier beads in spinner flask cultures for MSCs expansion and compared to that of conventional monolayer cultures and static microcarrier cultures. Isolation and characterization of bone marrow derived MSCs were conducted from six adult New Zealand white rabbits. Analysis of cell morphology on microcarriers and culture plates at different time points (D0, D3, D10, D14) during cell culture were performed using scanning electron microscopy and bright field microscopy. Cell proliferation rates and cell number were measured over a period of 14 days, respectively followed by post-expansion characterization. MTT proliferation assay demonstrated a 3.20 fold increase in cell proliferation rates in MSCs cultured on microcarriers in spinner flask as compared to monolayer cultures (p < 0.05). Cell counts at day 14 were higher in those seeded on stirred microcarrier cultures (6.24 ± 0.0420 cells/ml) × 10(5) as compared to monolayer cultures (0.22 ± 0.004 cells/ml) × 10(5) and static microcarrier cultures (0.20 ± 0.002 cells/ml) × 10(5). Scanning electron microscopy demonstrated an increase in cell colonization of the cells on the microcarriers in stirred cultures. Bead-expanded MSCs were successfully differentiated into osteogenic and chondrogenic lineages. This system offers an improved and efficient alternative for culturing MSCs with preservation to their phenotype and multipotentiality.
Fulltext Exclusive breastfeeding practice during first six months of an infant's life in Bangladesh: a country based cross-sectional study

Hossain M, Islam A, Kamarul T, Hossain G

BMC Pediatr, 2018 03 02;18(1):93.
PMID: 29499670 DOI: 10.1186/s12887-018-1076-0

BACKGROUND: Breastfeeding offers incredible health benefits to both child and mother. It is suggested by World Health Organization that an able mother should practice and maintain exclusive breastfeeding for first six months of her infant's life. The objective of this study was to determine the prevalence and factors associated with exclusive breastfeeding for first six months of an infant's life in Bangladesh.
METHODS: Data was extracted from Bangladesh Demographic and Health Survey (BDHS-2014). BDHS-2014 collected data from 17,863 Bangladeshi married women in reproductive age from the entire country using two stages stratified cluster sampling. We included only mothers having at least one child currently aged not less than 6 months. Mothers who did not have child to breastfeed, some incomplete information and missing samples were excluded from the data set and consequently 3541 mothers were considered in the present study. Chi-square test, binary logistic regression models were used in this study.
RESULTS: The prevalence of exclusive breastfeeding (EBF) for first six months of an infant's life in Bangladesh was 35.90%. Binary multivariable logistic regression model demonstrated that relatively less educated mothers were more likely to exclusively breastfeed their children than higher educated mothers. (AOR = 2.28, 95% CI: 1.05-4.93; p
Evaluating the Protective Effects and Mechanisms of Diallyl Disulfide on Interlukin-1β-Induced Oxidative Stress and Mitochondrial Apoptotic Signaling Pathways in Cultured Chondrocytes

Hosseinzadeh A, Jafari D, Kamarul T, Bagheri A, Sharifi AM

J Cell Biochem, 2017 Jul;118(7):1879-1888.
PMID: 28169456 DOI: 10.1002/jcb.25907

The protective effects and mechanisms of DADS on IL-1β-mediated oxidative stress and mitochondrial apoptosis were investigated in C28I2 human chondrocytes. The effect of various concentrations of DADS (1, 5 10, 25, 50, and 100 μM) on C28I2 cell viability was evaluated in different times (2, 4, 8, 16, and 24 h) to obtain the non-cytotoxic concentrations of drug by MTT-assay. The protective effect of non-toxic concentrations of DADS on experimentally induced oxidative stress and apoptosis by IL-1β in C28I2 was evaluated. The effects of DADS on IL-1β-induced intracellular ROS production and lipid peroxidation were detected and the proteins expression of Nrf2, Bax, Bcl-2, caspase-3, total and phosphorylated JNK, and P38 MAPKs were analyzed by Western blotting. The mRNA expression of detoxifying phase II/antioxidant enzymes including heme oxygenase-1, NAD(P)H quinine oxidoreductase, glutathione S-transferase-P1, catalase, superoxide dismutase-1, glutathione peroxidase-1, -3, -4 were evaluated by reverse transcription-polymerase chain reaction. DADS in 1, 5, 10, and 25 μM concentrations had no cytotoxic effect after 24 h. Pretreatment with DADS remarkably increased Nrf2 nuclear translocation as well as the genes expression of detoxifying phase II/antioxidant enzymes and reduced IL-1β-induced elevation of ROS, lipid peroxidation, Bax/Bcl-2 ratio, caspase-3 activation, and JNK and P38 phosphorylation. DADS could considerably reduce IL-1β-induced oxidative stress and consequent mitochondrial apoptosis, as the major mechanisms of chondrocyte cell death in an experimental model of osteoarthritis. It may be considered as natural product in protecting OA-induced cartilage damage in clinical setting. J. Cell. Biochem. 118: 1879-1888, 2017. © 2017 Wiley Periodicals, Inc.
Fulltext Enhancement of mesenchymal stem cell chondrogenesis with short-term low intensity pulsed electromagnetic fields

Parate D, Franco-Obregón A, Fröhlich J, Beyer C, Abbas AA, Kamarul T, et al.

Sci Rep, 2017 08 25;7(1):9421.
PMID: 28842627 DOI: 10.1038/s41598-017-09892-w

Pulse electromagnetic fields (PEMFs) have been shown to recruit calcium-signaling cascades common to chondrogenesis. Here we document the effects of specified PEMF parameters over mesenchymal stem cells (MSC) chondrogenic differentiation. MSCs undergoing chondrogenesis are preferentially responsive to an electromagnetic efficacy window defined by field amplitude, duration and frequency of exposure. Contrary to conventional practice of administering prolonged and repetitive exposures to PEMFs, optimal chondrogenic outcome is achieved in response to brief (10 minutes), low intensity (2 mT) exposure to 6 ms bursts of magnetic pulses, at 15 Hz, administered only once at the onset of chondrogenic induction. By contrast, repeated exposures diminished chondrogenic outcome and could be attributed to calcium entry after the initial induction. Transient receptor potential (TRP) channels appear to mediate these aspects of PEMF stimulation, serving as a conduit for extracellular calcium. Preventing calcium entry during the repeated PEMF exposure with the co-administration of EGTA or TRP channel antagonists precluded the inhibition of differentiation. This study highlights the intricacies of calcium homeostasis during early chondrogenesis and the constraints that are placed on PEMF-based therapeutic strategies aimed at promoting MSC chondrogenesis. The demonstrated efficacy of our optimized PEMF regimens has clear clinical implications for future regenerative strategies for cartilage.
Elevated plasma and synovial fluid interleukin-8 and interleukin-18 may be associated with the pathogenesis of knee osteoarthritis

Koh SM, Chan CK, Teo SH, Singh S, Merican A, Ng WM, et al.

Knee, 2020 Jan;27(1):26-35.
PMID: 31917106 DOI: 10.1016/j.knee.2019.10.028

PURPOSE: Osteoarthritis (OA) of the knee is a multifactorial degenerative disease typically defined as the 'wear and tear' of articular joint cartilage. However, recent studies suggest that OA is a disease arising from chronic low-grade inflammation. We conducted a study to investigate the relationship between chronic inflammatory mediators present in both the systemic peripheral blood system and localised inflammation in synovial fluid (SF) of OA and non-OA knees; and subsequently made direct comparative analyses to understand the mechanisms that may underpin the processes involved in OA.
METHODS: 20-Plex proteins were quantified using Human Magnetic Luminex® assay (R&D Systems, USA) from plasma and SF of OA (n = 14) and non-OA (n = 14) patients. Ingenuity Pathway Analysis (IPA) software was used to predict the relationship and possible interaction of molecules pertaining to OA.
RESULTS: There were significant differences in plasma level for matrix metalloproteinase (MMP)-3, interleukin (IL)-27, IL-8, IL-4, tumour necrosis factor-alpha, MMP-1, IL-15, IL-21, IL-10, and IL-1 beta between the groups, as well as significant differences in SF level for IL-15, IL-8, vascular endothelial growth factor (VEGF), MMP-1, and IL-18. Our predictive OA model demonstrated that toll-like receptor (TLR) 2, macrophage migration inhibitory factor (MIF), TLR4 and IL-1 were the main regulators of IL-1B, IL-4, IL-8, IL-10, IL-15, IL-21, IL-27, MMP-1 and MMP-3 in the plasma system; whilst IL-1B, TLR4, IL-1, and basigin (BSG) were the regulators of IL-4, IL-8, IL-10, IL-15, IL-18, IL-21, IL-27, MMP-1, and MMP-3 in the SF system.
CONCLUSION: The elevated plasma IL-8 and SF IL-18 may be associated with the pathogenesis of OA via the activation of MMP-3.
Elastomeric biocomposite of silver-containing mesoporous bioactive glass and poly(1,8-octanediol citrate): Physiochemistry and in vitro antibacterial capacity in tissue engineering applications

Pourshahrestani S, Zeimaran E, Kadri NA, Gargiulo N, Jindal HM, Hasikin K, et al.

Mater Sci Eng C Mater Biol Appl, 2019 May;98:1022-1033.
PMID: 30812986 DOI: 10.1016/j.msec.2019.01.022

A novel series of silver-doped mesoporous bioactive glass/poly(1,8-octanediol citrate) (AgMBG/POC) elastomeric biocomposite scaffolds were successfully constructed by a salt-leaching technique for the first time and the effect of inclusion of different AgMBG contents (5, 10, and 20 wt%) on physicochemical and biological properties of pure POC elastomer was evaluated. Results indicated that AgMBG particles were uniformly dispersed in the POC matrix and increasing the AgMBG concentration into POC matrix up to 20 wt% enhanced thermal behaviour, mechanical properties and water uptake ability of the composite scaffolds compared to those from POC. The 20%AgMBG/POC additionally showed higher degradation rate in Tris(hydroxymethyl)-aminomethane-HCl (Tris-HCl) compared with pure POC and lost about 26% of its initial weight after soaking for 28 days. The AgMBG phase incorporation also significantly endowed the resulting composite scaffolds with efficient antibacterial properties against Escherichia coli and Staphylococcus aureus bacteria while preserving their favorable biocompatibility with soft tissue cells (i.e., human dermal fibroblast cells). Taken together, our results suggest that the synergistic effect of both AgMBG and POC make these newly designed AgMBG/POC composite scaffold an attractive candidate for soft tissue engineering applications.
Effect of torsional loading on compressive fatigue behaviour of trabecular bone

Fatihhi SJ, Rabiatul AA, Harun MN, Kadir MR, Kamarul T, Syahrom A

J Mech Behav Biomed Mater, 2016 Feb;54:21-32.
PMID: 26410762 DOI: 10.1016/j.jmbbm.2015.09.006

The present study reports the effects of combined torsional and compressive cyclic loading on trabecular bone in order to mimic true physiological conditions and thereby provides improved data that represents clinical and real life conditions. However, only compressive behaviour is evaluated in most previous studies of bone mechanics. From the monotonic evaluation, it is observed that lower stress is needed for the onset of microcrack in the sample under torsional loading, compared to the stress needed in compression. Trabecular bone samples were subjected to a combination of torsion and compression fatigue at different stress levels during which they were compared to compressive axial fatigue. The stress levels were determined by considering the monotonic strength at 25-50% for both compressive and shear stresses. Significant decrease in fatigue lifetime is observed in between samples of pure compression fatigue and those with superpositioned torsional loading (p<0.05). The reduction in fatigue lifetime became more evident at a high torsional stress level. In this case, the failure of the sample is said to be 'torsional dominant'. Fatigue behaviour of bovine trabecular bone begins with plastic deformation, followed by strain accumulation and modulus reduction. As the strain rate increases, more energy dissipates and the sample finally failed. Further, the analysis of fractograph revealed something on the trabeculae by bending in sample with superpositioned torsional loading. In conclusion, torsional loading decreases the quality of the trabecular properties in terms of stiffness, life and structural integrity. It is hoped that results from this study will improve the understanding of the behaviour of trabecular bone under combined fatigue and help to develop future assessments of trabecular failure.
Effect of growth differentiation factor 5 on the proliferation and tenogenic differentiation potential of human mesenchymal stem cells in vitro

Tan SL, Ahmad RE, Ahmad TS, Merican AM, Abbas AA, Ng WM, et al.

Cells Tissues Organs (Print), 2012;196(4):325-38.
PMID: 22653337

The use of growth differentiation factor 5 (GDF-5) in damaged tendons has been shown to improve tendon repair. It has been hypothesized that further improvements may be achieved when GDF-5 is used to promote cell proliferation and induce tenogenic differentiation in human bone marrow-derived mesenchymal stem cells (hMSCs). However, the optimal conditions required to produce these effects on hMSCs have not been demonstrated in previous studies. A study to determine cell proliferation and tenogenic differentiation in hMSCs exposed to different concentrations of GDF-5 (0, 5, 25, 50, 100 and 500 ng/ml) was thus conducted. No significant changes were observed in the cell proliferation rate in hMSCs treated at different concentrations of GDF-5. GDF-5 appeared to induce tenogenic differentiation at 100 ng/ml, as reflected by (1) a significant increase in total collagen expression, similar to that of the primary native human tenocyte culture; (2) a significant upregulation in candidate tenogenic marker gene expression, i.e. scleraxis, tenascin-C and type-I collagen; (3) the ratio of type-I collagen to type-III collagen expression was elevated to levels similar to that of human tenocyte cultures, and (4) a significant downregulation of the non-tenogenic marker genes runt-related transcription factor 2 and sex determining region Y (SRY)-box 9 at day 7 of GDF-5 induction, further excluding hMSC differentiation into other lineages. In conclusion, GDF-5 does not alter the proliferation rates of hMSCs, but, instead, induces an optimal tenogenic differentiation response at 100 ng/ml.
Effect of Chitosan Nanoparticle-Loaded Thymus serpyllum on Hydrogen Peroxide-Induced Bone Marrow Stromal Cell Damage

Baig S, Azizan AHS, Raghavendran HRB, Natarajan E, Naveen S, Murali MR, et al.

Stem Cells Int, 2019;2019:5142518.
PMID: 30956670 DOI: 10.1155/2019/5142518

We have determined the protective effects of Thymus serpyllum (TS) extract and nanoparticle-loaded TS on hydrogen peroxide-induced cell death of mesenchymal stromal cells (MSCs) in vitro. Gas chromatography-mass spectroscopy confirmed the spectrum of active components in the extract. Out of the three different extracts, the hexane extract showed significant free radical scavenging activity. Treatment of MSCs with H2O2 (hydrogen peroxide) significantly increased intracellular cell death; however, pretreatment with TS extract and nanoparticle-loaded TS (200 μg/ml) suppressed H2O2-induced elevation of Cyt-c and MMP13 and increased the survival rates of MSCs. H2O2-induced (0.1 mM) changes in cytokines were attenuated in the extract and nanoparticles by pretreatment and cotreatment at two time points (p < 0.05). H2O2 increased cell apoptosis. In contrast, treatment with nanoparticle-loaded TS suppressed the percentage of apoptosis considerably (p < 0.05). Therefore, TS may be considered as a potential candidate for enhancing the effectiveness of MSC transplantation in cell therapy.
Effect of 17β-estradiol on mediators involved in mesenchymal stromal cell trafficking in cell therapy of diabetes

Mirzamohammadi S, Aali E, Najafi R, Kamarul T, Mehrabani M, Aminzadeh A, et al.

Cytotherapy, 2015 Jan;17(1):46-57.
PMID: 25457279 DOI: 10.1016/j.jcyt.2014.06.009

Mesenchymal stromal cells (MSCs) have shown great promise for cell therapy of a wide range of diseases such as diabetes. However, insufficient viability of transplanted cells reaching to damaged tissues has limited their potential therapeutic effects. Expression of estrogen receptors on stem cells may suggest a role for 17β-estradiol (E2) in regulating some functions in these cells. There is evidence that E2 enhances homing of stem cells. Induction of hypoxia-inducible factor-1α (HIF-1α) by E2 and the profound effect of HIF-1α on migration of cells have previously been demonstrated. We investigated the effect of E2 on major mediators involved in trafficking and subsequent homing of MSCs both in vitro and in vivo in diabetic rats.

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