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  1. Law JX, Chowdhury SR, Saim AB, Idrus RBH
    J Tissue Viability, 2017 Aug;26(3):208-215.
    PMID: 28615133 DOI: 10.1016/j.jtv.2017.05.003
    Advances in tissue engineering led to the development of various tissue-engineered skin substitutes (TESS) for the treatment of skin injuries. The majority of the autologous TESS required lengthy and costly cell expansion process to fabricate. In this study, we determine the possibility of using a low density of human skin cells suspended in platelet-rich plasma (PRP)-enriched medium to promote the healing of full-thickness skin wounds. To achieve this, full-thickness wounds of size 1.767 cm2 were created at the dorsum part of nude mice and treated with keratinocytes (2 × 104 cells/cm2) and fibroblasts (3 × 104 cells/cm2) suspended in 10% PRP-enriched medium. Wound examination was conducted weekly and the animals were euthanized after 2 weeks. Gross examination showed that re-epithelialization was fastest in the PRP+cells group at both day 7 and 14, followed by the PRP group and NT group receiving no treatment. Only the PRP+cells group achieved complete wound closure by 2 weeks. Epidermal layer was presence in the central region of the wound of the PRP+cells and PRP groups but absence in the NT group. Comparison between the PRP+cells and PRP groups showed that the PRP+cells-treated wound was more mature as indicated by the presence of thinner epidermis with single cell layer thick basal keratinocytes and less cellular dermis. In summary, the combination of low cell density and diluted PRP creates a synergistic effect which expedites the healing of full-thickness wounds. This combination has the potential to be developed as a rapid wound therapy via the direct application of freshly harvested skin cells in diluted PRP.
  2. Zahari NK, Idrus RBH, Chowdhury SR
    Int J Mol Sci, 2017 Oct 30;18(11).
    PMID: 29084180 DOI: 10.3390/ijms18112242
    Myoblasts, the contractile cells of skeletal muscle, have been invaluable for fundamental studies of muscle development and clinical applications for muscle loss. A major limitation to the myoblast-based therapeutic approach is contamination with non-contractile fibroblasts, which overgrow during cell expansion. To overcome these limitations, this study was carried out to establish a 3D culture environment using nanofiber scaffolds to enrich the myoblast population during construct formation. Poly(methyl methacrylate) (PMMA) nanofiber (PM) scaffolds were fabricated using electrospinning techniques and coated with extracellular matrix (ECM) proteins, such as collagen or laminin, in the presence or absence of genipin. A mixed population of myoblasts and fibroblasts was isolated from human skeletal muscle tissues and cultured on plain surfaces, as well as coated and non-coated PM scaffolds. PMMA can produce smooth fibers with an average diameter of 360 ± 50 nm. Adsorption of collagen and laminin on PM scaffolds is significantly enhanced in the presence of genipin, which introduces roughness to the nanofiber surface without affecting fiber diameter and mechanical properties. It was also demonstrated that laminin-coated PM scaffolds significantly enhance myoblast proliferation (0.0081 ± 0.0007 h-1) and migration (0.26 ± 0.04 μm/min), while collagen-coated PM scaffolds favors fibroblasts proliferation (0.0097 ± 0.0009 h-1) and migration (0.23 ± 0.03 μm/min). Consequently, the myoblast population was enriched on laminin-coated PM scaffolds throughout the culture process. Therefore, laminin coating of nanofiber scaffolds could be a potential scaffold for the development of a tissue-engineered muscle substitute.
  3. Ude CC, Miskon A, Idrus RBH, Abu Bakar MB
    Mil Med Res, 2018 02 26;5(1):7.
    PMID: 29502528 DOI: 10.1186/s40779-018-0154-9
    The dynamic nature of modern warfare, including threats and injuries faced by soldiers, necessitates the development of countermeasures that address a wide variety of injuries. Tissue engineering has emerged as a field with the potential to provide contemporary solutions. In this review, discussions focus on the applications of stem cells in tissue engineering to address health risks frequently faced by combatants at war. Human development depends intimately on stem cells, the mysterious precursor to every kind of cell in the body that, with proper instruction, can grow and differentiate into any new tissue or organ. Recent reports have suggested the greater therapeutic effects of the anti-inflammatory, trophic, paracrine and immune-modulatory functions associated with these cells, which induce them to restore normal healing and tissue regeneration by modulating immune reactions, regulating inflammation, and suppressing fibrosis. Therefore, the use of stem cells holds significant promise for the treatment of many battlefield injuries and their complications. These applications include the treatment of injuries to the skin, sensory organs, nervous system tissues, the musculoskeletal system, circulatory/pulmonary tissues and genitals/testicles and of acute radiation syndrome and the development of novel biosensors. The new research developments in these areas suggest that solutions are being developed to reduce critical consequences of wounds and exposures suffered in warfare. Current military applications of stem cell-based therapies are already saving the lives of soldiers who would have died in previous conflicts. Injuries that would have resulted in deaths previously now result in wounds today; similarly, today's permanent wounds may be reduced to tomorrow's bad memories with further advances in stem cell-based therapies.
  4. Sulaiman SB, Idrus RBH, Hwei NM
    Polymers (Basel), 2020 Oct 19;12(10).
    PMID: 33086577 DOI: 10.3390/polym12102404
    The gelatin microsphere (GM) provides an attractive option for tissue engineering due to its versatility, as reported by various studies. This review presents the history, characteristics of, and the multiple approaches to, the production of GM, and in particular, the water in oil emulsification technique. Thereafter, the application of GM as a drug delivery system for cartilage diseases is introduced. The review then focusses on the emerging application of GM as a carrier for cells and biologics, and biologics delivery within a cartilage construct. The influence of GM on chondrocytes in terms of promoting chondrocyte proliferation and chondrogenic differentiation is highlighted. Furthermore, GM seeded with cells has been shown to have a high tendency to form aggregates; hence the concept of using GM seeded with cells as the building block for the formation of a complex tissue construct. Despite the advancement in GM research, some issues must still be addressed, particularly the improvement of GM's ability to home to defect sites. As such, the strategy of intraarticular injection of GM seeded with antibody-coated cells is proposed. By addressing this in future studies, a better-targeted delivery system, that would result in more effective intervention, can be achieved.
  5. Kamil K, Yazid MD, Idrus RBH, Kumar J
    PMID: 32575426 DOI: 10.3390/ijerph17124404
    Recent advances in phytomedicine have explored some potential candidates for nerve regeneration, including hydroxytyrosol (HT). This study was undertaken to explore the potential effects of HT on human Schwann cells' proliferation. Methods: The primary human Schwann cell (hSC) was characterized, and the proliferation rate of hSC supplemented with various concentrations of HT was determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle analysis and protein expression of glial fibrillary acidic protein (GFAP) and p75 nerve growth factor receptor (p75 NGFR) were evaluated via the immunofluorescence technique. Results: In vitro culture of hSCs revealed spindle-like, bipolar morphology with the expression of specific markers of hSC. Hydroxytyrosol at 10 and 20 ng/mL significantly increased the proliferation of hSCs by 30.12 ± 5.9% and 47.8 ± 6.7% compared to control (p < 0.05). Cell cycle analysis showed that HT-treated hSCs have a higher proliferation index (16.2 ± 0.2%) than the control (12.4 ± 0.4%) (p < 0.01). In addition, HT significantly increased the protein expression of GFAP and p75NGFR (p < 0.05). Conclusion: HT stimulates the proliferation of hSCs in vitro, indicated by a significant increase in the hSC proliferation index and protein expression of hSCs' proliferation markers, namely p75 NGFR and GFAP.
  6. Salamt N, Idrus RBH, Kashim MIAM, Mokhtar MH
    Saudi Pharm J, 2021 Jul;29(7):740-750.
    PMID: 34400869 DOI: 10.1016/j.jsps.2021.05.006
    Camel urine has traditionally been used to treat multiple human diseases and possesses the most beneficial effects amongst the urine of other animals. However, scientific review evaluating the anticancer, antiplatelet, gastroprotective and hepatoprotective effects of camel urine is still scarce. Thus, this scoping review aimed to provide scientific evidence on the therapeutic potentials of camel urine. Three databases were searched to identify relevant articles (Web of Science, PubMed and Scopus) up to September 2020. Original articles published in English that investigated the effects of camel urine in various diseases were included. The literature search identified six potential articles that met all the inclusion criteria. Three articles showed that camel urine possesses cytotoxic activities against different types of cancer cells. Two studies revealed camel urine's protective effects against liver toxicity and gastric ulcers, whilst another study showed the role of camel urine as an antiplatelet agent. All studies demonstrated significant positive effects with different effective dosages. Thus, camel urine shows promising therapeutic potential in treating human diseases, especially cancer. However, the standardised dosage and potential side effects should be determined before camel urine could be offered as an alternative treatment.
  7. Ansari AS, Yazid MD, Sainik NQAV, Razali RA, Saim AB, Idrus RBH
    Stem Cells Int, 2018;2018:2406462.
    PMID: 30534156 DOI: 10.1155/2018/2406462
    Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are emerging as a promising source for bone regeneration in the treatment of bone defects. Previous studies have reported the ability of WJ-MSCs to be induced into the osteogenic lineage. The purpose of this review was to systematically assess the potential of WJ-MSC differentiation into the osteogenic lineage. A comprehensive search was conducted in Medline via Ebscohost and Scopus, where relevant studies published between 1961 and 2018 were selected. The main inclusion criteria were that articles must be primary studies published in English evaluating osteogenic induction of WJ-MSCs. The literature search identified 92 related articles, but only 18 articles met the inclusion criteria. These include two animal studies, three articles containing both in vitro and in vivo assessments, and 13 articles on in vitro studies, all of which are discussed in this review. There were two types of osteogenic induction used in these studies, either chemical or physical. The studies demonstrate that WJ-MSCs are able to differentiate into osteogenic lineage and promote osteogenesis. In light of these observations, it is suggested that WJ-MSCs can be a potential source of stem cells for osteogenic induction, as an alternative to bone marrow-derived mesenchymal stem cells.
  8. Maarof M, Mohd Nadzir M, Sin Mun L, Fauzi MB, Chowdhury SR, Idrus RBH, et al.
    Polymers (Basel), 2021 Feb 08;13(4).
    PMID: 33567703 DOI: 10.3390/polym13040508
    The current strategy for rapid wound healing treatment involves combining a biomaterial and cell-secreted proteins or biomolecules. This study was aimed at characterizing 3-dimensional (3D) collagen hydrogels fortified with dermal fibroblast-conditioned medium (DFCM) as a readily available acellular skin substitute. Confluent fibroblasts were cultured with serum-free keratinocyte-specific medium (KM1 and KM2) and fibroblast-specific medium (FM) to obtain DFCM. Subsequently, the DFCM was mixed with collagen (Col) hydrogel and chondroitin-4-sulphate (C4S) to fabricate 3D constructs termed Col/C4S/DFCM-KM1, Col/C4S/DFCM-KM2, and Col/C4S/DFCM-FM. The constructs successfully formed soft, semi-solid and translucent hydrogels within 1 h of incubation at 37 °C with strength of <2.5 Newton (N). The Col/C4S/DFCM demonstrated significantly lower turbidity compared to the control groups. The Col/C4S/DFCM also showed a lower percentage of porosity (KM1: 35.15 ± 9.76%; KM2: 6.85 ± 1.60%; FM: 14.14 ± 7.65%) compared to the Col (105.14 ± 11.87%) and Col/C4S (143.44 ± 27.72%) constructs. There were no changes in both swelling and degradation among all constructs. Fourier transform infrared spectrometry showed that all groups consisted of oxygen-hydrogen bonds (O-H) and amide I, II, and III. In conclusion, the Col/C4S/DFCM constructs maintain the characteristics of native collagen and can synergistically deliver essential biomolecules for future use in skin therapeutic applications.
  9. Busra FM, Lokanathan Y, Nadzir MM, Saim A, Idrus RBH, Chowdhury SR
    Malays J Med Sci, 2017 Mar;24(2):33-43.
    PMID: 28894402 DOI: 10.21315/mjms2017.24.2.5
    INTRODUCTION: Collagen type I is widely used as a biomaterial for tissue-engineered substitutes. This study aimed to fabricate different three-dimensional (3D) scaffolds using ovine tendon collagen type I (OTC-I), and compare the attachment, proliferation and morphological features of human dermal fibroblasts (HDF) on the scaffolds.

    METHODS: This study was conducted between the years 2014 to 2016 at the Tissue Engineering Centre, UKM Medical Centre. OTC-I was extracted from ovine tendon, and fabricated into 3D scaffolds in the form of sponge, hydrogel and film. A polystyrene surface coated with OTC-I was used as the 2D culture condition. Genipin was used to crosslink the OTC-I. A non-coated polystyrene surface was used as a control. The mechanical strength of OTC-I scaffolds was evaluated. Attachment, proliferation and morphological features of HDF were assessed and compared between conditions.

    RESULTS: The mechanical strength of OTC-I sponge was significantly higher than that of the other scaffolds. OTC-I scaffolds and the coated surface significantly enhanced HDF attachment and proliferation compared to the control, but no differences were observed between the scaffolds and coated surface. In contrast, the morphological features of HDF including spreading, filopodia, lamellipodia and actin cytoskeletal formation differed between conditions.

    CONCLUSION: OTC-I can be moulded into various scaffolds that are biocompatible and thus could be suitable as scaffolds for developing tissue substitutes for clinical applications and in vitro tissue models. However, further study is required to determine the effect of morphological properties on the functional and molecular properties of HDF.

  10. Man RC, Sulaiman N, Idrus RBH, Ariffin SHZ, Wahab RMA, Yazid MD
    Stem Cells Int, 2019;2019:4596150.
    PMID: 31772587 DOI: 10.1155/2019/4596150
    Cell-free treatment is emerging as an alternative to cell delivery to promote endogenous regeneration using cell-derived factors. The purpose of this article was to systematically review studies of the effects of the dental stem cell secretome on nerve regeneration. PubMed and Scopus databases were used where searched and related studies were selected. The primary search identified 36 articles with the utilized keywords; however, only 13 articles met the defined inclusion criteria. Eight out of thirteen articles included in vivo and in vitro studies. We classified the dental stem cell-derived secretome with its nerve regeneration potential. All studies demonstrated that dental stem cell-derived factors promote neurotrophic effects that can mechanistically stimulate nerve regeneration in neurodegenerative diseases and nerve injury. This data collection will enable researchers to gather information to create a precise formulation for future prescribed treatments.
  11. Kamil K, Yazid MD, Idrus RBH, Das S, Kumar J
    Front Neurol, 2019;10:87.
    PMID: 30941082 DOI: 10.3389/fneur.2019.00087
    Demyelinating diseases represent a spectrum of disorders that impose significant burden on global economy and society. Generally, the prognosis of these diseases is poor and there is no available cure. In recent decades, research has shed some light on the biology and physiology of Schwann cells and its neuroprotective effects in the peripheral nervous system (PNS). Insults to the PNS by various infectious agents, genetic predisposition and immune-related mechanisms jeopardize Schwann cell functions and cause demyelination. To date, there are no effective and reliable biomarkers for PNS-related diseases. Here, we aim to review the following: pathogenesis of various types of peripheral demyelinating diseases such as Guillain-Barre syndrome, Chronic Inflammatory Demyelinating Polyradiculoneuropathy, Anti-Myelin Associated Glycoprotein Neuropathy, POEMS syndrome, and Charcot-Marie-Tooth disease; emerging novel biomarkers for peripheral demyelinating diseases, and Schwann cell associated markers for demyelination.
  12. Koh B, Sulaiman N, Fauzi MB, Law JX, Ng MH, Idrus RBH, et al.
    Cell Biosci, 2020;10:75.
    PMID: 32518618 DOI: 10.1186/s13578-020-00438-8
    Stem cell-based regenerative medicine is a promising approach for tissue reconstruction. However, a large number of cells are needed in a typical clinical study, where conventional monolayer cultures might pose a limitation for scale-up. The purpose of this review was to systematically assess the application of microcarriers in Mesenchymal Stem Cell cultures. A comprehensive search was conducted in Medline via Ebscohost, Pubmed, and Scopus, and relevant studies published between 2015 and 2019 were selected. The literature search identified 53 related studies, but only 14 articles met the inclusion criteria. These include 7 utilised commercially available microcarriers, while the rest were formulated based on different surface characteristics, all of which are discussed in this review. Current applications of microcarriers were focused on MSC expansion and induction of MSCs into different lineages. These studies demonstrated that MSCs could proliferate in a microcarrier culture system in-fold compared to monolayer cultures, and the culture system could simulate a three-dimensional environment which induces cell differentiation. However, detailed studies are still required before this system were to be adapted into the scale of GMP manufacturing.
  13. Hussin HM, Lawi MM, Haflah NHM, Kassim AYM, Idrus RBH, Lokanathan Y
    Tissue Eng Regen Med, 2020 04;17(2):237-251.
    PMID: 32036567 DOI: 10.1007/s13770-019-00235-6
    BACKGROUND: Centella asiatica (L.) is a plant with neuroprotective and neuroregenerative properties; however, its effects on the neurodifferentiation of mesenchymal stem cells (MSCs) and on peripheral nerve injury are poorly explored. This study aimed to investigate the effects of C. asiatica (L.)-neurodifferentiated MSCs on the regeneration of peripheral nerve in a critical-size defect animal model.

    METHODS: Nerve conduit was developed using decellularised artery seeded with C. asiatica-neurodifferentiated MSCs (ndMSCs). A 1.5 cm sciatic nerve injury in Sprague-Dawley rat was bridged with reversed autograft (RA) (n = 3, the gold standard treatment), MSC-seeded conduit (MC) (n = 4) or ndMSC-seeded conduit (NC) (n = 4). Pinch test and nerve conduction study were performed every 2 weeks for a total of 12 weeks. At the 12th week, the conduits were examined by histology and transmission electron microscopy.

    RESULTS: NC implantation improved the rats' sensory sensitivity in a similar manner to RA. At the 12th week, nerve conduction velocity was the highest in NC compared with that of RA and MC. Axonal regeneration was enhanced in NC and RA as shown by the expression of myelin basic protein (MBP). The average number of myelinated axons was significantly higher in NC than in MC but significantly lower than in RA. The myelin sheath thickness was higher in NC than in MC but lower than in RA.

    CONCLUSION: NC showed promising effects on nerve regeneration and functional restoration similar to those of RA. These findings revealed the neuroregenerative properties of C. asiatica and its potential as an alternative strategy for the treatment of critical size nerve defect.

  14. Imran SAM, Yazid MD, Idrus RBH, Maarof M, Nordin A, Razali RA, et al.
    Int J Mol Sci, 2021 Apr 09;22(8).
    PMID: 33918710 DOI: 10.3390/ijms22083888
    Epithelial-Mesenchymal Transition (EMT) was first discovered during the transition of cells from the primitive streak during embryogenesis in chicks. It was later discovered that EMT holds greater potential in areas other than the early development of cells and tissues since it also plays a vital role in wound healing and cancer development. EMT can be classified into three types based on physiological functions. EMT type 3, which involves neoplastic development and metastasis, has been the most thoroughly explored. As EMT is often found in cancer stem cells, most research has focused on its association with other factors involving cancer progression, including telomeres. However, as telomeres are also mainly involved in aging, any possible interaction between the two would be worth noting, especially as telomere dysfunction also contributes to cancer and other age-related diseases. Ascertaining the balance between degeneration and cancer development is crucial in cell biology, in which telomeres function as a key regulator between the two extremes. The essential roles that EMT and telomere protection have in aging reveal a potential mutual interaction that has not yet been explored, and which could be used in disease therapy. In this review, the known functions of EMT and telomeres in aging are discussed and their potential interaction in age-related diseases is highlighted.
  15. Nike DU, Katas H, Mohd NF, Hiraoka Y, Tabata Y, Idrus RBH, et al.
    Polymers (Basel), 2021 Sep 17;13(18).
    PMID: 34578052 DOI: 10.3390/polym13183152
    The irregular deep chronic wound is a grand challenge to be healed due to multiple factors including slow angiogenesis that causing regenerated tissue failure. The narrow gap of deep wounds could hinder and slow down normal wound healing. Thus, the current study aimed to develop a polymerised genipin-crosslinked gelatin (gelipin) hydrogel (GNP_GH) as a potential biodegradable filler for the abovementioned limitations. Briefly, GNP_GH bioscaffolds have been developed successfully within three-minute polymerisation at room temperature (22-24 °C). The physicochemical and biocompatibility of GNP_GH bioscaffolds were respectively evaluated. Amongst GNP_GH groups, the 0.1%GNP_GH10% displayed the highest injectability (97.3 ± 0.6%). Meanwhile, the 0.5%GNP_GH15% degraded within more than two weeks with optimum swelling capacity (108.83 ± 15.7%) and higher mechanical strength (22.6 ± 3.9 kPa) than non-crosslinked gelatin hydrogel 15% (NC_GH15%). Furthermore, 0.1%GNP_GH15% offered higher porosity (>80%) and lower wettability (48.7 ± 0.3) than NC_GH15%. Surface and cross-section SEM photographs displayed an interconnected porous structure for all GNP_GH groups. The EDX spectra and maps represented no major changes after GNP modification. Moreover, no toxicity effect of GNP_GH against dermal fibroblasts was shown during the biocompatibility test. In conclusion, the abovementioned findings indicated that gelipin has excellent physicochemical properties and acceptable biocompatibility as an acellular rapid treatment for future use in irregular deep cutaneous wounds.
  16. Man RC, Yong TK, Hwei NM, Halim WHWA, Zahidin AZM, Ramli R, et al.
    Mol. Vis., 2017;23:810-822.
    PMID: 29225457
    Various clinical disorders and injuries, such as chemical, thermal, or mechanical injuries, may lead to corneal loss that results in blindness. PURPOSE: The aims of this study were to differentiate human buccal mucosa (BMuc) into corneal epithelial-like cells, to fabricate engineered corneal tissue using buccal mucosal epithelial cells, and to reconstruct a damaged corneal epithelium in a nude rat model.

    Methods: BMuc were subjected to 10 d of induction factors to investigate the potential of cells to differentiate into corneal lineages.

    Results: Corneal stem cell markers β1-integrin, C/EBPδ, ABCG2, p63, and CK3 were upregulated in the gene expression analysis in induced BMuc, whereas CK3 and p63 showed significant protein expression in induced BMuc compared to the uninduced cells. BMuc were then left to reach 80% confluency after differential trypsinization. The cells were harvested and cultivated on a commercially available untreated air-dried amniotic membrane (AM) in a Transwell system in induction medium. The corneal constructs were fabricated and then implanted into damaged rat corneas for up to 8 weeks. A significant improvement was detected in the treatment group at 8 weeks post-implantation, as revealed by slit lamp biomicroscopy analysis. The structure and thickness of the corneal layer were also analyzed using histological staining and time-domain optical coherence tomography scans and were found to resemble a native corneal layer. The protein expression for CK3 and p63 were continuously detected throughout the corneal epithelial layer in the corneal construct.

    Conclusions: In conclusion, human BMuc can be induced to express a corneal epithelial-like phenotype. The addition of BMuc improves corneal clarity, prevents vascularization, increases corneal thickness and stromal alignment, and appears to have no adverse effect on the host after implantation.

  17. Lim J, Razi ZRM, Law JX, Nawi AM, Idrus RBH, Chin TG, et al.
    Tissue Eng Regen Med, 2018 Feb;15(1):75-87.
    PMID: 30603536 DOI: 10.1007/s13770-017-0086-6
    Umbilical cord (UC) is a discarded product from the operating theatre and a ready source of mesenchymal stromal cells (MSCs). MSCs from UC express both embryonic and adult mesenchymal stem cell markers and are known to be hypoimmunogenic and non-tumorigenic and thus suitable for allogeneic cell transplantation. Our study aimed to determine the degree of immunotolerance and bone-forming capacity of osteodifferentiated human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs) from different segments of UC in an allogenic setting. UCs were obtained from healthy donors delivering a full-term infant by elective Caesarean section. hWJ-MSCs were isolated from 3 cm length segment from the maternal and foetal ends of UCs. Three-dimensional fibrin constructs were formed and implanted intramuscularly into immunocompetent mice. The mice were implanted with 1) fibrin construct with maternal hWJ-MSCs, 2) fibrin construct with foetal hWJ-MSCs, or 3) fibrin without cells; the control group received sham surgery. After 1 month, the lymphoid organs were analysed to determine the degree of immune rejection and bone constructs were analysed to determine the amount of bone formed. A pronounced immune reaction was noted in the fibrin group. The maternal segment constructs demonstrated greater osteogenesis than the foetal segment constructs. Both maternal and foetal segment constructs caused minimal immune reaction and thus appear to be safe for allogeneic bone transplant. The suppression of inflammation may be a result of increased anti-inflammatory cytokine production mediated by the hWJ-MSC. In summary, this study demonstrates the feasibility of using bone constructs derived from hWJ-MSCs in an allogenic setting.
  18. Hassan MNFB, Yazid MD, Yunus MHM, Chowdhury SR, Lokanathan Y, Idrus RBH, et al.
    Stem Cells Int, 2020;2020:9529465.
    PMID: 32733574 DOI: 10.1155/2020/9529465
    Mesenchymal stem cells (MSCs) are multipotent stem cells with strong immunosuppressive property that renders them an attractive source of cells for cell therapy. MSCs have been studied in multiple clinical trials to treat liver diseases, peripheral nerve damage, graft-versus-host disease, autoimmune diseases, diabetes mellitus, and cardiovascular damage. Millions to hundred millions of MSCs are required per patient depending on the disease, route of administration, frequency of administration, and patient body weight. Multiple large-scale cell expansion strategies have been described in the literature to fetch the cell quantity required for the therapy. In this review, bioprocessing strategies for large-scale expansion of MSCs were systematically reviewed and discussed. The literature search in Medline and Scopus databases identified 26 articles that met the inclusion criteria and were included in this review. These articles described the large-scale expansion of 7 different sources of MSCs using 4 different bioprocessing strategies, i.e., bioreactor, spinner flask, roller bottle, and multilayered flask. The bioreactor, spinner flask, and multilayered flask were more commonly used to upscale the MSCs compared to the roller bottle. Generally, a higher expansion ratio was achieved with the bioreactor and multilayered flask. Importantly, regardless of the bioprocessing strategies, the expanded MSCs were able to maintain its phenotype and potency. In summary, the bioreactor, spinner flask, roller bottle, and multilayered flask can be used for large-scale expansion of MSCs without compromising the cell quality.
  19. Koh B, Sulaiman N, Ismadi SNSW, Ramli R, Yunus SSM, Idrus RBH, et al.
    Biol Proced Online, 2021 Sep 15;23(1):18.
    PMID: 34521356 DOI: 10.1186/s12575-021-00155-7
    BACKGROUND: In the area of oral and maxillofacial surgery, regenerative endodontics aims to present alternative options to conventional treatment strategies. With continuous advances in regenerative medicine, the source of cells used for pulp tissue regeneration is not only limited to mesenchymal stem cells as the non-mesenchymal stem cells have shown capabilities too. In this review, we are systematically assessing the recent findings on odontoblastic differentiation induction with scaffold and non-scaffold approaches.

    METHODS: A comprehensive search was conducted in Pubmed, and Scopus, and relevant studies published between 2015 and 2020 were selected following the PRISMA guideline. The main inclusion criteria were that articles must be revolving on method for osteoblast differentiation in vitro study. Therefore, in vivo and human or animal clinical studies were excluded. The search outcomes identified all articles containing the word "odontoblast", "differentiation", and "mesenchymal stem cell".

    RESULTS: The literature search identified 99 related studies, but only 11 articles met the inclusion criteria. These include 5 odontoblastic differentiation induction with scaffold, 6 inductions without scaffolds. The data collected were characterised into two main categories: type of cells undergo odontoblastic differentiation, and odontoblastic differentiation techniques using scaffolds or non-scaffold.

    CONCLUSION: Based on the data analysis, the scaffold-based odontoblastic induction method seems to be a better option compared to the non-scaffold method. In addition of that, the combination of growth factors in scaffold-based methods could possibly enhance the differentiation. Thus, further detailed studies are still required to understand the mechanism and the way to enhance odontoblastic differentiation.

  20. Chan AML, Ng AMH, Mohd Yunus MH, Idrus RBH, Law JX, Yazid MD, et al.
    Nutrients, 2021 Jul 22;13(8).
    PMID: 34444658 DOI: 10.3390/nu13082497
    Metabolic syndrome (MetS) is the physiological clustering of hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, and insulin resistance. The MetS-related chronic illnesses encompass obesity, the cardiovascular system, renal operation, hepatic function, oncology, and mortality. To perform pre-clinical research, it is imperative that these symptoms be successfully induced and optimized in lower taxonomy. Therefore, novel and future applications for a disease model, if proven valid, can be extrapolated to humans. MetS model establishment is evaluated based on the significance of selected test parameters, paradigm shifts from new discoveries, and the accessibility of the latest technology or advanced methodologies. Ultimately, the outcome of animal studies should be advantageous for human clinical trials and solidify their position in advanced medicine for clinicians to treat and adapt to serious or specific medical situations. Rodents (Rattus norvegicus and Mus musculus) have been ideal models for mammalian studies since the 18th century and have been mapped extensively. This review compiles and compares studies published in the past five years between the multitude of rodent comparative models. The response factors, niche parameters, and replicability of diet protocols are also compiled and analyzed to offer insight into MetS-related disease-specific modelling.
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