Displaying publications 1 - 20 of 36 in total

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  1. Fulltext A Three-Dimensional Xeno-Free Culture Condition for Wharton's Jelly-Mesenchymal Stem Cells: The Pros and Cons
    Koh B, Sulaiman N, Fauzi MB, Law JX, Ng MH, Yuan TL, et al.
    Int J Mol Sci, 2023 Feb 13;24(4).
    PMID: 36835154 DOI: 10.3390/ijms24043745
    Xeno-free three-dimensional cultures are gaining attention for mesenchymal stem cell (MSCs) expansion in clinical applications. We investigated the potential of xeno-free serum alternatives, human serum and human platelet lysate, to replace the current conventional use of foetal bovine serum for subsequent MSCs microcarrier cultures. In this study, Wharton's Jelly MSCs were cultured in nine different media combinations to identify the best xeno-free culture media for MSCs culture. Cell proliferation and viability were identified, and the cultured MSCs were characterised in accordance with the minimal criteria for defining multipotent mesenchymal stromal cells by the International Society for Cellular Therapy (ISCT). The selected culture media was then used in the microcarrier culture of MSCs to determine the potential of a three-dimensional culture system in the expansion of MSCs for future clinical applications, and to identify the immunomodulatory potential of cultured MSCs. Low Glucose DMEM (LG) + Human Platelet (HPL) lysate media appeared to be good candidates for replacing conventional MSCs culture media in our monolayer culture system. MSCs cultured in LG-HPL achieved high cell yield, with characteristics that remained as described by ISCT, although the overall mitochondrial activity of the cells was lower than the control and the subsequent effects remained unknown. MSC microcarrier culture, on the other hand, showed comparable cell characteristics with monolayer culture, yet had stagnated cell proliferation, which is potentially due to the inactivation of FAK. Nonetheless, both the MSCs monolayer culture and the microcarrier culture showed high suppressive activity on TNF-α, and only the MSC microcarrier culture has a better suppression of IL-1 secretion. In conclusion, LG-HPL was identified as a good xeno-free media for WJMSCs culture, and although further mechanistic research is needed, the results show that the xeno-free three-dimensional culture maintained MSC characteristics and improved immunomodulatory activities, suggesting the potential of translating the monolayer culture into this culture system in MSC expansion for future clinical application.
  2. A comparative study of skin cell activities in collagen and fibrin constructs
    Law JX, Musa F, Ruszymah BH, El Haj AJ, Yang Y
    Med Eng Phys, 2016 Sep;38(9):854-61.
    PMID: 27349492 DOI: 10.1016/j.medengphy.2016.05.017
    Collagen and fibrin are widely used in tissue engineering due to their excellent biocompatibility and bioactivities that support in vivo tissue formation. These two hydrogels naturally present in different wound healing stages with different regulatory effects on cells, and both of them are mechanically weak in the reconstructed hydrogels. We conducted a comparative study by the growth of rat dermal fibroblasts or dermal fibroblasts and epidermal keratinocytes together in collagen and fibrin constructs respectively with and without the reinforcement of electrospun poly(lactic acid) nanofiber mesh. Cell proliferation, gel contraction and elastic modulus of the constructs were measured on the same gels at multiple time points during the 22 day culturing period using multiple non-destructive techniques. The results demonstrated considerably different cellular activities within the two types of constructs. Co-culturing keratinocytes with fibroblasts in the collagen constructs reduced the fibroblast proliferation, collagen contraction and mechanical strength at late culture point regardless of the presence of nanofibers. Co-culturing keratinocytes with fibroblasts in the fibrin constructs promoted fibroblast proliferation but exerted no influence on fibrin contraction and mechanical strength. The presence of nanofibers in the collagen and fibrin constructs played a favorable role on the fibroblast proliferation when keratinocytes were absent. Thus, this study exhibited new evidence of the strong cross-talk between keratinocytes and fibroblasts, which can be used to control fibroblast proliferation and construct contraction. This cross-talk activity is extracellular matrix-dependent in terms of the fibrous network morphology, density and strength.
  3. Characteristics and clinical applications of Wharton's jelly-derived mesenchymal stromal cells
    Liau LL, Ruszymah BHI, Ng MH, Law JX
    Curr Res Transl Med, 2020 01;68(1):5-16.
    PMID: 31543433 DOI: 10.1016/j.retram.2019.09.001
    Mesenchymal stromal cells (MSCs) are widely used in the clinic because they involve fewer ethical issues and safety concerns compared to other stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). MSCs derived from umbilical cord Wharton's jelly (WJ-MSCs) have excellent proliferative potential and a faster growth rate and can retain their multipotency for more passages in vitro compared to adult MSCs from bone marrow or adipose tissue. WJ-MSCs are used clinically for repairing tissue injuries of the spinal cord, liver and heart with the aim of regenerating tissue. On the other hand, WJ-MSCs are also used clinically to ameliorate immune-mediated diseases based on their ability to modulate immune responses. In the field of tissue engineering, WJ-MSCs capable of differentiating into multiple cell lineages have been used to produce a variety of engineered tissues in vitro that can then be transplanted in vivo. This review discusses the characteristics of WJ-MSCs, the differences between WJ-MSCs and adult MSCs, clinical studies involving WJ-MSCs and future perspectives of WJ-MSC research and clinical applications. To summarize, WJ-MSCs have shown promise in treating a variety of diseases clinically. However, most clinical trials/studies reported thus far are relatively smaller in scale. The collected evidence is insufficient to support the routine use of WJ-MSC therapy in the clinic. Thus, rigorous clinical trials are needed in the future to obtain more information on WJ-MSC therapy safety and efficacy.
  4. Collagen Type I: A Versatile Biomaterial
    Chowdhury SR, Mh Busra MF, Lokanathan Y, Ng MH, Law JX, Cletus UC, et al.
    Adv Exp Med Biol, 2018 10 26;1077:389-414.
    PMID: 30357700 DOI: 10.1007/978-981-13-0947-2_21
    Collagen type I is the most abundant matrix protein in the human body and is highly demanded in tissue engineering, regenerative medicine, and pharmaceutical applications. To meet the uprising demand in biomedical applications, collagen type I has been isolated from mammalians (bovine, porcine, goat and rat) and non-mammalians (fish, amphibian, and sea plant) source using various extraction techniques. Recent advancement enables fabrication of collagen scaffolds in multiple forms such as film, sponge, and hydrogel, with or without other biomaterials. The scaffolds are extensively used to develop tissue substitutes in regenerating or repairing diseased or damaged tissues. The 3D scaffolds are also used to develop in vitro model and as a vehicle for delivering drugs or active compounds.
  5. Fulltext Comparing the Therapeutic Potential of Stem Cells and their Secretory Products in Regenerative Medicine
    Foo JB, Looi QH, Chong PP, Hassan NH, Yeo GEC, Ng CY, et al.
    Stem Cells Int, 2021;2021:2616807.
    PMID: 34422061 DOI: 10.1155/2021/2616807
    Cell therapy involves the transplantation of human cells to replace or repair the damaged tissues and modulate the mechanisms underlying disease initiation and progression in the body. Nowadays, many different types of cell-based therapy are developed and used to treat a variety of diseases. In the past decade, cell-free therapy has emerged as a novel approach in regenerative medicine after the discovery that the transplanted cells exerted their therapeutic effect mainly through the secretion of paracrine factors. More and more evidence showed that stem cell-derived secretome, i.e., growth factors, cytokines, and extracellular vesicles, can repair the injured tissues as effectively as the cells. This finding has spurred a new idea to employ secretome in regenerative medicine. Despite that, will cell-free therapy slowly replace cell therapy in the future? Or are these two modes of treatment still needed to address different diseases and conditions? This review provides an indepth discussion about the values of stem cells and secretome in regenerative medicine. In addition, the safety, efficacy, advantages, and disadvantages of using these two modes of treatment in regenerative medicine are also critically reviewed.
  6. Comparison of three different skin substitutes in promoting wound healing in an ovine model
    Subramaniam T, Shaiful Hadi N, Sulaiman S, Fauzi MB, Hj Idrus RB, Chowdhury SR, et al.
    Burns, 2021 Aug 20.
    PMID: 34893370 DOI: 10.1016/j.burns.2021.08.012
    Skin substitutes are designed dressings intended to promote wound closure. In previous in vitro and in vivo studies on small animal, an acellular skin patch made of collagen hydrogel with dermal fibroblast conditioned medium (Col-DFCM), a collagen sponge scaffold with freshly harvested skin cells (OTC), and a platelet-rich-plasma gel with freshly harvested skin cells (PRP) have been developed and tested for immediate treatment of full-thickness wound. However, to determine the safety and efficacy of these skin patches for clinical applications, further study in a large animal model is needed. The aim of this study is to evaluate the potential of Col-DFCM, OTC and PRP in treating full-thickness wound in an ovine model via histological analysis and immunohistochemistry staining were performed, with the untreated (NT) group serving as the control. Gross examination was conducted on day 7, 14 and 21 to determine the wound closure rate. The findings of percentage of wound size reduction showed that the wound healed fastest in the presence of Col-DFCM (91.34 ± 23.35%) followed by OTC (84.49 ± 23.13%), PRP (77.73 ± 20.9%) and NT group (73.94 ± 23.71%). Histological evaluation with Hematoxylin & Eosin (H & E) and Masson's trichrome staining was used to study the structure of the wound area. The results showed that OTC treated wound was more mature as indicated by the presence of a thinner epidermis followed by the Col-DFCM, PRP and NT group. Immunohistochemistry analysis also confirmed the integrity and maturity of the regenerated skin, with positive expression of cytokeratin 10 (CK10) and involucrin in the epidermal layer. In conclusion, Col-DFCM, OTC and PRP treatments promote healing of full-thickness wound and have the potential to be used clinically for rapid treatment of full-thickness wound.
  7. Fulltext Current Progress in Tendon and Ligament Tissue Engineering
    Lim WL, Liau LL, Ng MH, Chowdhury SR, Law JX
    Tissue Eng Regen Med, 2019 Dec;16(6):549-571.
    PMID: 31824819 DOI: 10.1007/s13770-019-00196-w
    BACKGROUND: Tendon and ligament injuries accounted for 30% of all musculoskeletal consultations with 4 million new incidences worldwide each year and thus imposed a significant burden to the society and the economy. Damaged tendon and ligament can severely affect the normal body movement and might lead to many complications if not treated promptly and adequately. Current conventional treatment through surgical repair and tissue graft are ineffective with a high rate of recurrence.

    METHODS: In this review, we first discussed the anatomy, physiology and pathophysiology of tendon and ligament injuries and its current treatment. Secondly, we explored the current role of tendon and ligament tissue engineering, describing its recent advances. After that, we also described stem cell and cell secreted product approaches in tendon and ligament injuries. Lastly, we examined the role of the bioreactor and mechanical loading in in vitro maturation of engineered tendon and ligament.

    RESULTS: Tissue engineering offers various alternative ways of treatment from biological tissue constructs to stem cell therapy and cell secreted products. Bioreactor with mechanical stimulation is instrumental in preparing mature engineered tendon and ligament substitutes in vitro.

    CONCLUSIONS: Tissue engineering showed great promise in replacing the damaged tendon and ligament. However, more study is needed to develop ideal engineered tendon and ligament.

  8. Development of an In Vitro Cardiac Ischemic Model Using Primary Human Cardiomyocytes
    Hafez P, Chowdhury SR, Jose S, Law JX, Ruszymah BHI, Mohd Ramzisham AR, et al.
    Cardiovasc Eng Technol, 2018 09;9(3):529-538.
    PMID: 29948837 DOI: 10.1007/s13239-018-0368-8
    Developing experimental models to study ischemic heart disease is necessary for understanding of biological mechanisms to improve the therapeutic approaches for restoring cardiomyocytes function following injury. The aim of this study was to develop an in vitro hypoxic/re-oxygenation model of ischemia using primary human cardiomyocytes (HCM) and define subsequent cytotoxic effects. HCM were cultured in serum and glucose free medium in hypoxic condition with 1% O2 ranging from 30 min to 12 h. The optimal hypoxic exposure time was determined using Hypoxia Inducible Factor 1α (HIF-1α) as the hypoxic marker. Subsequently, the cells were moved to normoxic condition for 3, 6 and 9 h to replicate the re-oxygenation phase. Optimal period of hypoxic/re-oxygenation was determined based on 50% mitochondrial injury via 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay and cytotoxicity via lactate dehydrogenase (LDH) assay. It was found that the number of cells expressing HIF-1α increased with hypoxic time and 3 h was sufficient to stimulate the expression of this marker in all the cells. Upon re-oxygenation, mitochondrial activity reduced significantly whereas the cytotoxicity increased significantly with time. Six hours of re-oxygenation was optimal to induce reversible cell injury. The injury became irreversible after 9 h as indicated by > 60% LDH leakage compared to the control group cultured in normal condition. Under optimized hypoxic reoxygenation experimental conditions, mesenchymal stem cells formed nanotube with ischemic HCM and facilitated transfer of mitochondria suggesting the feasibility of using this as a model system to study molecular mechanisms of myocardial injury and rescue.
  9. Fulltext Early Spatiotemporal Patterns and Population Characteristics of the COVID-19 Pandemic in Southeast Asia
    Zhu M, Kleepbua J, Guan Z, Chew SP, Tan JW, Shen J, et al.
    Healthcare (Basel), 2021 Sep 16;9(9).
    PMID: 34574997 DOI: 10.3390/healthcare9091220
    This observational study aims to investigate the early disease patterns of coronavirus disease 2019 (COVID-19) in Southeast Asia, consequently providing historical experience for further interventions. Data were extracted from official websites of the WHO and health authorities of relevant countries. A total of 1346 confirmed cases of COVID-19, with 217 recoveries and 18 deaths, were reported in Southeast Asia as of 16 March 2020. The basic reproductive number (R0) of COVID-19 in the region was estimated as 2.51 (95% CI:2.31 to 2.73), and there were significant geographical variations at the subregional level. Early transmission dynamics were examined with an exponential regression model: y = 0.30e0.13x (p < 0.01, R2 = 0.96), which could help predict short-term incidence. Country-level disease burden was positively correlated with Human Development Index (r = 0.86, p < 0.01). A potential early shift in spatial diffusion patterns and a spatiotemporal cluster occurring in Malaysia and Singapore were detected. Demographic analyses of 925 confirmed cases indicated a median age of 44 years and a sex ratio (male/female) of 1.25. Age may play a significant role in both susceptibilities and outcomes. The COVID-19 situation in Southeast Asia is challenging and unevenly geographically distributed. Hence, enhanced real-time surveillance and more efficient resource allocation are urgently needed.
  10. Fulltext Electrospun Collagen Nanofibers and Their Applications in Skin Tissue Engineering
    Law JX, Liau LL, Saim A, Yang Y, Idrus R
    Tissue Eng Regen Med, 2017 Dec;14(6):699-718.
    PMID: 30603521 DOI: 10.1007/s13770-017-0075-9
    Electrospinning is a simple and versatile technique to fabricate continuous fibers with diameter ranging from micrometers to a few nanometers. To date, the number of polymers that have been electrospun has exceeded 200. In recent years, electrospinning has become one of the most popular scaffold fabrication techniques to prepare nanofiber mesh for tissue engineering applications. Collagen, the most abundant extracellular matrix protein in the human body, has been electrospun to fabricate biomimetic scaffolds that imitate the architecture of native human tissues. As collagen nanofibers are mechanically weak in nature, it is commonly cross-linked or blended with synthetic polymers to improve the mechanical strength without compromising the biological activity. Electrospun collagen nanofiber mesh has high surface area to volume ratio, tunable diameter and porosity, and excellent biological activity to regulate cell function and tissue formation. Due to these advantages, collagen nanofibers have been tested for the regeneration of a myriad of tissues and organs. In this review, we gave an overview of electrospinning, encompassing the history, the instrument settings, the spinning process and the parameters that affect fiber formation, with emphasis given to collagen nanofibers' fabrication and application, especially the use of collagen nanofibers in skin tissue engineering.
  11. Fulltext Establishing SW1353 Chondrocytes as a Cellular Model of Chondrolysis
    Pang KL, Chow YY, Leong LM, Law JX, Ghafar NA, Soelaiman IN, et al.
    Life (Basel), 2021 Mar 25;11(4).
    PMID: 33805920 DOI: 10.3390/life11040272
    Osteoarthritis (OA) is the most common degenerative joint disease characterised by chondrocyte cell death. An in vitro model of chondrocyte cell death may facilitate drug discovery in OA management. In this study, the cytotoxicity and mode of cell death of SW1353 chondrocytes treated with 24 h of OA inducers, including interleukin-1β (IL-1β), hydrogen peroxide (H2O2) and monosodium iodoacetate (MIA), were investigated. The microscopic features, oxidative (isoprostane) and inflammatory markers (tumour necrosis factor-alpha; TNF-α) for control and treated cells were compared. Our results showed that 24 h of H2O2 and MIA caused oxidative stress and a concentration-dependent reduction of SW1353 cell viability without TNF-α level upregulation. H2O2 primarily induced chondrocyte apoptosis with the detection of blebbing formation, cell shrinkage and cellular debris. MIA induced S-phase arrest on chondrocytes with a reduced number of attached cells but without significant cell death. On the other hand, 24 h of IL-1β did not affect the cell morphology and viability of SW1353 cells, with a significant increase in intracellular TNF-α levels without inducing oxidative stress. In conclusion, each OA inducer exerts differential effects on SW1353 chondrocyte cell fate. IL-1β is suitable in the inflammatory study but not for chondrocyte cell death. H2O2 and MIA are suitable for inducing chondrocyte cell death and growth arrest, respectively.
  12. Fulltext Feasibility of Human Platelet Lysate as an Alternative to Foetal Bovine Serum for In Vitro Expansion of Chondrocytes
    Liau LL, Hassan MNFB, Tang YL, Ng MH, Law JX
    Int J Mol Sci, 2021 Jan 28;22(3).
    PMID: 33525349 DOI: 10.3390/ijms22031269
    Osteoarthritis (OA) is a degenerative joint disease that affects a lot of people worldwide. Current treatment for OA mainly focuses on halting or slowing down the disease progress and to improve the patient's quality of life and functionality. Autologous chondrocyte implantation (ACI) is a new treatment modality with the potential to promote regeneration of worn cartilage. Traditionally, foetal bovine serum (FBS) is used to expand the chondrocytes. However, the use of FBS is not ideal for the expansion of cells mean for clinical applications as it possesses the risk of animal pathogen transmission and animal protein transfer to host. Human platelet lysate (HPL) appears to be a suitable alternative to FBS as it is rich in biological factors that enhance cell proliferation. Thus far, HPL has been found to be superior in promoting chondrocyte proliferation compared to FBS. However, both HPL and FBS cannot prevent chondrocyte dedifferentiation. Discrepant results have been reported for the maintenance of chondrocyte redifferentiation potential by HPL. These differences are likely due to the diversity in the HPL preparation methods. In the future, more studies on HPL need to be performed to develop a standardized technique which is capable of producing HPL that can maintain the chondrocyte redifferentiation potential reproducibly. This review discusses the in vitro expansion of chondrocytes with FBS and HPL, focusing on its capability to promote the proliferation and maintain the chondrogenic characteristics of chondrocytes.
  13. Full-thickness skin wound healing using autologous keratinocytes and dermal fibroblasts with fibrin: bilayered versus single-layered substitute
    Idrus RB, Rameli MA, Low KC, Law JX, Chua KH, Latiff MB, et al.
    Adv Skin Wound Care, 2014 Apr;27(4):171-80.
    PMID: 24637651 DOI: 10.1097/01.ASW.0000445199.26874.9d
    Split-skin grafting (SSG) is the gold standard treatment for full-thickness skin defects. For certain patients, however, an extensive skin lesion resulted in inadequacies of the donor site. Tissue engineering offers an alternative approach by using a very small portion of an individual's skin to harvest cells for propagation and biomaterials to support the cells for implantation. The objective of this study was to determine the effectiveness of autologous bilayered tissue-engineered skin (BTES) and single-layer tissue-engineered skin composed of only keratinocytes (SLTES-K) or fibroblasts (SLTES-F) as alternatives for full-thickness wound healing in a sheep model. Full-thickness skin biopsies were harvested from adult sheep. Isolated fibroblasts were cultured using medium Ham's F12: Dulbecco modified Eagle medium supplemented with 10% fetal bovine serum, whereas the keratinocytes were cultured using Define Keratinocytes Serum Free Medium. The BTES, SLTES-K, and SLTES-F were constructed using autologous fibrin as a biomaterial. Eight full-thickness wounds were created on the dorsum of the body of the sheep. On 4 wounds, polyvinyl chloride rings were used as chambers to prevent cell migration at the edge. The wounds were observed at days 7, 14, and 21. After 3 weeks of implantation, the sheep were euthanized and the skins were harvested. The excised tissues were fixed in formalin for histological examination via hematoxylin-eosin, Masson trichrome, and elastin van Gieson staining. The results showed that BTES, SLTES-K, and SLTES-F promote wound healing in nonchambered and chambered wounds, and BTES demonstrated the best healing potential. In conclusion, BTES proved to be an effective tissue-engineered construct that can promote the healing of full-thickness skin lesions. With the support of further clinical trials, this procedure could be an alternative to SSG for patients with partial- and full-thickness burns.
  14. Fulltext In Vitro Cell Proliferation and Migration Properties of Oral Mucosal Fibroblasts: A Comparative Study on the Effects of Cord Blood- and Peripheral Blood-Platelet Lysate
    Azmi AF, Yahya MAAM, Azhar NA, Ibrahim N, Ghafar NA, Ghani NAA, et al.
    Int J Mol Sci, 2023 Mar 17;24(6).
    PMID: 36982842 DOI: 10.3390/ijms24065775
    Cord blood-platelet lysate (CB-PL), containing growth factors such as a platelet-derived growth factor, has a similar efficacy to peripheral blood-platelet lysate (PB-PL) in initiating cell growth and differentiation, which makes it a unique alternative to be implemented into oral ulceration healing. This research study aimed to compare the effectiveness of CB-PL and PB-PL in promoting oral wound closure in vitro. Alamar blue assay was used to determine the optimal concentration of CB-PL and PB-PL in enhancing the proliferation of human oral mucosal fibroblasts (HOMF). The percentage of wound closure was measured using the wound-healing assay for CB-PL and PB-PL at the optimal concentration of 1.25% and 0.3125%, respectively. The gene expressions of cell phenotypic makers (Col. I, Col. III, elastin and fibronectin) were determined via qRT-PCR. The concentrations of PDGF-BB were quantified using ELISA. We found that CB-PL was as effective as PB-PL in promoting wound-healing and both PL were more effective compared to the control (CTRL) group in accelerating the cell migration in the wound-healing assay. The gene expressions of Col. III and fibronectin were significantly higher in PB-PL compared to CB-PL. The PDGF-BB concentration of PB-PL was the highest and it decreased after the wound closed on day 3. Therefore, we concluded that PL from both sources can be a beneficial treatment for wound-healing, but PB-PL showed the most promising wound-healing properties in this study.
  15. Large-Scale Expansion of Human Mesenchymal Stem Cells
    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.
  16. Mesenchymal Stem Cell Transplantation for the Treatment of Age-Related Musculoskeletal Frailty
    Mahindran E, Law JX, Ng MH, Nordin F
    Int J Mol Sci, 2021 Sep 29;22(19).
    PMID: 34638883 DOI: 10.3390/ijms221910542
    Projected life expectancy continues to grow worldwide owing to the advancement of new treatments and technologies leading to rapid growth of geriatric population. Thus, age-associated diseases especially in the musculoskeletal system are becoming more common. Loss of bone (osteoporosis) and muscle (sarcopenia) mass are conditions whose prevalence is increasing because of the change in population distribution in the world towards an older mean age. The deterioration in the bone and muscle functions can cause severe disability and seriously affects the patients' quality of life. Currently, there is no treatment to prevent and reverse age-related musculoskeletal frailty. Existing interventions are mainly to slow down and control the signs and symptoms. Mesenchymal stem cell (MSC) transplantation is a promising approach to attenuate age-related musculoskeletal frailty. This review compiles the present knowledge of the causes and changes of the musculoskeletal frailty and the potential of MSC transplantation as a regenerative therapy for age-related musculoskeletal frailty.
  17. Fulltext Mesenchymal Stromal Cells from the Maternal Segment of Human Umbilical Cord is Ideal for Bone Regeneration in Allogenic Setting
    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. Fulltext Molecular Phylogenesis and Spatiotemporal Spread of SARS-CoV-2 in Southeast Asia
    Zhu M, Shen J, Zeng Q, Tan JW, Kleepbua J, Chew I, et al.
    Front Public Health, 2021 07 30;9:685315.
    PMID: 34395364 DOI: 10.3389/fpubh.2021.685315
    Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented challenge to public health in Southeast Asia, a tropical region with limited resources. This study aimed to investigate the evolutionary dynamics and spatiotemporal patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the region. Materials and Methods: A total of 1491 complete SARS-CoV-2 genome sequences from 10 Southeast Asian countries were downloaded from the Global Initiative on Sharing Avian Influenza Data (GISAID) database on November 17, 2020. The evolutionary relationships were assessed using maximum likelihood (ML) and time-scaled Bayesian phylogenetic analyses, and the phylogenetic clustering was tested using principal component analysis (PCA). The spatial patterns of SARS-CoV-2 spread within Southeast Asia were inferred using the Bayesian stochastic search variable selection (BSSVS) model. The effective population size (Ne) trajectory was inferred using the Bayesian Skygrid model. Results: Four major clades (including one potentially endemic) were identified based on the maximum clade credibility (MCC) tree. Similar clustering was yielded by PCA; the first three PCs explained 46.9% of the total genomic variations among the samples. The time to the most recent common ancestor (tMRCA) and the evolutionary rate of SARS-CoV-2 circulating in Southeast Asia were estimated to be November 28, 2019 (September 7, 2019 to January 4, 2020) and 1.446 × 10-3 (1.292 × 10-3 to 1.613 × 10-3) substitutions per site per year, respectively. Singapore and Thailand were the two most probable root positions, with posterior probabilities of 0.549 and 0.413, respectively. There were high-support transmission links (Bayes factors exceeding 1,000) in Singapore, Malaysia, and Indonesia; Malaysia involved the highest number (7) of inferred transmission links within the region. A twice-accelerated viral population expansion, followed by a temporary setback, was inferred during the early stages of the pandemic in Southeast Asia. Conclusions: With available genomic data, we illustrate the phylogeography and phylodynamics of SARS-CoV-2 circulating in Southeast Asia. Continuous genomic surveillance and enhanced strategic collaboration should be listed as priorities to curb the pandemic, especially for regional communities dominated by developing countries.
  19. Fulltext Natural Killer Cell-Derived Extracellular Vesicles as a Promising Immunotherapeutic Strategy for Cancer: A Systematic Review
    Chan AML, Cheah JM, Lokanathan Y, Ng MH, Law JX
    Int J Mol Sci, 2023 Feb 16;24(4).
    PMID: 36835438 DOI: 10.3390/ijms24044026
    Cancer is the second leading contributor to global deaths caused by non-communicable diseases. The cancer cells are known to interact with the surrounding non-cancerous cells, including the immune cells and stromal cells, within the tumor microenvironment (TME) to modulate the tumor progression, metastasis and resistance. Currently, chemotherapy and radiotherapy are the standard treatments for cancers. However, these treatments cause a significant number of side effects, as they damage both the cancer cells and the actively dividing normal cells indiscriminately. Hence, a new generation of immunotherapy using natural killer (NK) cells, cytotoxic CD8+ T-lymphocytes or macrophages was developed to achieve tumor-specific targeting and circumvent the adverse effects. However, the progression of cell-based immunotherapy is hindered by the combined action of TME and TD-EVs, which render the cancer cells less immunogenic. Recently, there has been an increase in interest in using immune cell derivatives to treat cancers. One of the highly potential immune cell derivatives is the NK cell-derived EVs (NK-EVs). As an acellular product, NK-EVs are resistant to the influence of TME and TD-EVs, and can be designed for "off-the-shelf" use. In this systematic review, we examine the safety and efficacy of NK-EVs to treat various cancers in vitro and in vivo.
  20. Fulltext Physicochemical Properties and Biocompatibility of Electrospun Polycaprolactone/Gelatin Nanofibers
    Lim WL, Chowdhury SR, Ng MH, Law JX
    Int J Environ Res Public Health, 2021 04 29;18(9).
    PMID: 33947053 DOI: 10.3390/ijerph18094764
    Tissue-engineered substitutes have shown great promise as a potential replacement for current tissue grafts to treat tendon/ligament injury. Herein, we have fabricated aligned polycaprolactone (PCL) and gelatin (GT) nanofibers and further evaluated their physicochemical properties and biocompatibility. PCL and GT were mixed at a ratio of 100:0, 70:30, 50:50, 30:70, 0:100, and electrospun to generate aligned nanofibers. The PCL/GT nanofibers were assessed to determine the diameter, alignment, water contact angle, degradation, and surface chemical analysis. The effects on cells were evaluated through Wharton's jelly-derived mesenchymal stem cell (WJ-MSC) viability, alignment and tenogenic differentiation. The PCL/GT nanofibers were aligned and had a mean fiber diameter within 200-800 nm. Increasing the GT concentration reduced the water contact angle of the nanofibers. GT nanofibers alone degraded fastest, observed only within 2 days. Chemical composition analysis confirmed the presence of PCL and GT in the nanofibers. The WJ-MSCs were aligned and remained viable after 7 days with the PCL/GT nanofibers. Additionally, the PCL/GT nanofibers supported tenogenic differentiation of WJ-MSCs. The fabricated PCL/GT nanofibers have a diameter that closely resembles the native tissue's collagen fibrils and have good biocompatibility. Thus, our study demonstrated the suitability of PCL/GT nanofibers for tendon/ligament tissue engineering applications.
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