Displaying publications 1 - 20 of 242 in total

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  1. Volak A, LeRoy SG, Natasan JS, Park DJ, Cheah PS, Maus A, et al.
    J Neurooncol, 2018 Sep;139(2):293-305.
    PMID: 29767307 DOI: 10.1007/s11060-018-2889-2
    The malignant primary brain tumor, glioblastoma (GBM) is generally incurable. New approaches are desperately needed. Adeno-associated virus (AAV) vector-mediated delivery of anti-tumor transgenes is a promising strategy, however direct injection leads to focal transgene spread in tumor and rapid tumor division dilutes out the extra-chromosomal AAV genome, limiting duration of transgene expression. Intravenous (IV) injection gives widespread distribution of AAV in normal brain, however poor transgene expression in tumor, and high expression in non-target cells which may lead to ineffective therapy and high toxicity, respectively. Delivery of transgenes encoding secreted, anti-tumor proteins to tumor stromal cells may provide a more stable and localized reservoir of therapy as they are more differentiated than fast-dividing tumor cells. Reactive astrocytes and tumor-associated macrophage/microglia (TAMs) are stromal cells that comprise a large portion of the tumor mass and are associated with tumorigenesis. In mouse models of GBM, we used IV delivery of exosome-associated AAV vectors driving green fluorescent protein expression by specific promoters (NF-κB-responsive promoter and a truncated glial fibrillary acidic protein promoter), to obtain targeted transduction of TAMs and reactive astrocytes, respectively, while avoiding transgene expression in the periphery. We used our approach to express the potent, yet toxic anti-tumor cytokine, interferon beta, in tumor stroma of a mouse model of GBM, and achieved a modest, yet significant enhancement in survival compared to controls. Noninvasive genetic modification of tumor microenvironment represents a promising approach for therapy against cancers. Additionally, the vectors described here may facilitate basic research in the study of tumor stromal cells in situ.
    Matched MeSH terms: Stromal Cells/cytology; Stromal Cells/metabolism*
  2. Abu Kasim NH, Govindasamy V, Gnanasegaran N, Musa S, Pradeep PJ, Srijaya TC, et al.
    J Tissue Eng Regen Med, 2015 Dec;9(12):E252-66.
    PMID: 23229816 DOI: 10.1002/term.1663
    The discovery of mesenchymal stem cells (MSCs) from a myriad of tissues has triggered the initiative of establishing tailor-made stem cells for disease-specific therapy. Nevertheless, lack of understanding on the inherent differential propensities of these cells may restrict their clinical outcome. Therefore, a comprehensive study was done to compare the proliferation, differentiation, expression of cell surface markers and gene profiling of stem cells isolated from different sources, viz. bone marrow, Wharton's jelly, adipose tissue and dental pulp. We found that although all MSCs were phenotypically similar to each other, Wharton's jelly (WJ) MSCs and dental pulp stem cells (DPSCs) were highly proliferative as compared to bone marrow (BM) MSCs and adipose tissue (AD) MSCs. Moreover, indistinguishable cell surface characteristics and differentiation capacity were confirmed to be similar among all cell types. Based on gene expression profiling, we postulate that BM-MSCs constitutively expressed genes related to inflammation and immunodulation, whereas genes implicated in tissue development were highly expressed in AD-MSCs. Furthermore, the transcriptome profiling of WJ-MSCs and DPSCs revealed an inherent bias towards the neuro-ectoderm lineage. Based on our findings, we believe that there is no unique master mesenchymal stem cell that is appropriate to treat all target diseases. More precisely, MSCs from different sources exhibit distinct and unique gene expression signatures that make them competent to give rise to specific lineages rather than others. Therefore, stem cells should be subjected to rigorous characterization and utmost vigilance needs to be adopted in order to choose the best cellular source for a particular disease.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology; Mesenchymal Stromal Cells/metabolism*
  3. Fui LW, Lok MPW, Govindasamy V, Yong TK, Lek TK, Das AK
    J Tissue Eng Regen Med, 2019 12;13(12):2218-2233.
    PMID: 31648415 DOI: 10.1002/term.2966
    Mesenchymal stem cells (MSCs) transplantation seems to be a promising new therapy for diabetic wound healing (DWH), and currently, arrays of MSCs from various sources ranging from umbilical, adipose to dental sources are available as a treatment modality for this disease. However, it now appears that only a fraction of transplanted cells actually assimilate and survive in host tissues suggesting that the major mechanism by which stem cells participate in tissue repair are most likely related to their secretome level. These include a wide range of growth factors, cytokines, and chemokines, which can be found from the conditioned medium (CM) used to culture the cells. Basic studies and preclinical work confirm that the therapeutic effect of CMs are comparable with the application of stem cells. This review describes in detail the wound healing process in diabetes and the cellular and biological factors that influence the process. Subsequently, through a comprehensive literature search of studies related to wound healing in diabetics, we aim to provide an overview of scientific merits of using MSCs-CM in the treatment of diabetic wound as well as the significant caveats, which restricts its potential use in clinical set-ups. To our best knowledge, this is one of the first review papers that collect the importance of stem cells as an alternative treatment to the DWH. We anticipate that the success of this treatment will have a significant clinical impact on diabetic wounds.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism*
  4. Xu Z, Nan W, Zhang X, Sun Y, Yang J, Lu K, et al.
    J Mol Neurosci, 2018 Jun;65(2):222-233.
    PMID: 29845511 DOI: 10.1007/s12031-018-1075-5
    Mesenchymal stem cell (MSC) therapy is a promising prospect for the treatment of Alzheimer's disease (AD); however, the underlying mechanisms by which MSCs mediate positive effects are still unclear. We speculated that MSCs mediate microglial autophagy and enhance the clearance of Aβ. To test this hypothesis, we cultured BV2 microglial cells with umbilical cord mesenchymal stem cells conditioned medium (ucMSCs-CM) in the presence or absence of Aβ25-35 oligomers. We investigated BV2 cell proliferation, cell death, and Aβ25-35 phagocytosis as well as protein expression levels of LC3, Beclin-1, p62, insulin-degrading enzyme (IDE), and neprilysin (Nep) with western blotting. The results showed that ucMSCs-CM inhibited the proliferation and decreased cell death of BV2 cells induced by Aβ25-35. ucMSCs-CM also promoted the phagocytosis of Aβ25-35 by BV2 cells and changed the expression of autophagy-related proteins LC3, Beclin-1, and p62. Treatment also upregulated the expression of Aβ-degrading enzymes IDE and Nep. Furthermore, the culture medium in BV2 cells with Aβ25-35 and ucMSCs-CM prevented neuronal cell SH-SY5Y from cell death compared to control medium without ucMSCs-CM. Altogether, these data suggested that ucMSCs-CM protect microglial and neuronal cells from Aβ25-35-induced cell death and promote Aβ phagocytosis by modulating autophagy and enhancing the expression of Aβ-degrading enzymes in microglia.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism*
  5. Mamidi MK, Pal R, Govindasamy V, Zakaria Z, Bhonde R
    Med Hypotheses, 2011 Apr;76(4):599-601.
    PMID: 21277690 DOI: 10.1016/j.mehy.2011.01.010
    The staggering number of publications featuring the use of stem cells has revolutionized regenerative medicine research. Preclinical studies indicate that allogeneic human mesenchymal stem cells (MSCs) may be useful for the treatment of several clinical disorders, including sepsis, acute renal failure, acute myocardial infarction, and more recently, acute lung injury (ALI). However, considerable success would not be obtained in clinical trials due to poor survival of transplanted cells under the influence of inflammatory conditions. Despite robust approaches like cellular reprogramming, scaffolds and conditioned media have been tested to overcome this problem; however the success rate of these approaches remain questionable. Recently, pretreatment of bioactive compounds in vitro have been shown to suppress cell apoptosis and promote cell survival. Quite likely a similar phenomenon can take place in vivo. Based on such studies, we hypothesize that MSCs derived from human post-natal tissues could be conditioned and prepared for targeted disease therapy. Depending on the disease condition, the MSCs could be treated prior to delivery with appropriate bioactive compounds to allow them survive longer and perform a better role as biocatalyst. The advantage of this approach could be the tailor made availability of MSCs preconditioned with appropriate bioactive compounds for disease specific therapy. Therefore, the choice of suitable bioactive molecule is likely to enhance the efficacy of targeted stem cell therapy and preconditioning may provide a novel strategy in maximizing biological and functional properties of MSCs.
    Matched MeSH terms: Mesenchymal Stromal Cells/drug effects*; Mesenchymal Stromal Cells/physiology*
  6. Alkaisi A, Ismail AR, Mutum SS, Ahmad ZA, Masudi S, Abd Razak NH
    J Oral Maxillofac Surg, 2013 Oct;71(10):1758.e1-13.
    PMID: 24040948 DOI: 10.1016/j.joms.2013.05.016
    The main aim of the present study was to evaluate the capacity of stem cells from human exfoliated deciduous teeth (SHED) to enhance mandibular distraction osteogenesis (DO) in rabbits.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology
  7. Rengasamy M, Singh G, Fakharuzi NA, Siddikuzzaman, Balasubramanian S, Swamynathan P, et al.
    Stem Cell Res Ther, 2017 06 13;8(1):143.
    PMID: 28610623 DOI: 10.1186/s13287-017-0595-1
    BACKGROUND: Mesenchymal stromal cells (MSCs) from various tissues have shown moderate therapeutic efficacy in reversing liver fibrosis in preclinical models. Here, we compared the relative therapeutic potential of pooled, adult human bone marrow (BM)- and neonatal Wharton's jelly (WJ)-derived MSCs to treat CCl4-induced liver fibrosis in rats.

    METHODS: Sprague-Dawley rats were injected with CCl4 for 8 weeks to induce irreversible liver fibrosis. Ex-vivo expanded, pooled human MSCs obtained from BM and WJ were intravenously administered into rats with liver fibrosis at a dose of 10 × 106 cells/animal. Sham control and vehicle-treated animals served as negative and disease controls, respectively. The animals were sacrificed at 30 and 70 days after cell transplantation and hepatic-hydroxyproline content, histopathological, and immunohistochemical analyses were performed.

    RESULTS: BM-MSCs treatment showed a marked reduction in liver fibrosis as determined by Masson's trichrome and Sirius red staining as compared to those treated with the vehicle. Furthermore, hepatic-hydroxyproline content and percentage collagen proportionate area were found to be significantly lower in the BM-MSCs-treated group. In contrast, WJ-MSCs treatment showed less reduction of fibrosis at both time points. Immunohistochemical analysis of BM-MSCs-treated liver samples showed a reduction in α-SMA+ myofibroblasts and increased number of EpCAM+ hepatic progenitor cells, along with Ki-67+ and human matrix metalloprotease-1+ (MMP-1+) cells as compared to WJ-MSCs-treated rat livers.

    CONCLUSIONS: Our findings suggest that BM-MSCs are more effective than WJ-MSCs in treating liver fibrosis in a CCl4-induced model in rats. The superior therapeutic activity of BM-MSCs may be attributed to their expression of certain MMPs and angiogenic factors.

    Matched MeSH terms: Mesenchymal Stromal Cells/cytology
  8. Yap FL, Cheong SK, Ammu R, Leong CF
    Malays J Pathol, 2009 Dec;31(2):113-20.
    PMID: 20514854 MyJurnal
    In this study, we evaluated the biological properties of human mesenchymal stem cells transfected (hMSC) with a plasmid vector expressing human cytokine interleukin-12 (IL-12). Surface markers were analysed by immunophenotyping using flow cytometry. Differentiation capability was evaluated towards adipogenesis and osteogenesis. We demonstrated that successfully transfected hMSC retained their surface immunophenotypes and differentiation potential into adipocytes and osteocytes. These results indicate that hMSC may be a suitable vehicle for gene transduction.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*; Mesenchymal Stromal Cells/metabolism
  9. Wee AS, Lim CK, Merican AM, Ahmad TS, Kamarul T
    In Vitro Cell Dev Biol Anim, 2013 Jun;49(6):424-32.
    PMID: 23708918 DOI: 10.1007/s11626-013-9626-0
    In vitro cellular proliferation and the ability to undergo multilineage differentiation make bone marrow-derived multipotent stromal cells (MSCs) potentially useful for clinical applications. Several methods have been described to isolate a homogenous bone marrow-derived MSCs population; however, none has been proven most effective, mainly due to their effects on proliferation and differentiation capability of the isolated cells. It is hypothesized that our newly established total cell pooling method may provide a better alternative as compared to the standard isolation method (density gradient centrifugation method). For the total cell pooling method, MSCs were isolated from rabbit bone marrow and were subsequently cultured in the growth medium without further separation as in the standard isolation method. The total cell pooling method was 65 min faster than the standard isolation method in completing cell isolation. Nevertheless, both methods did not differ significantly in the number of primary viable cells and population doubling time in the cultures (p > 0.05). The isolated cells from both methods expressed CD29 and CD44 markers, but not CD45 markers. Furthermore, they displayed multilineage differentiation characteristics of chondroblasts, osteoblasts, and adipocytes. In conclusion, both methods provide similar efficiency in the isolation of rabbit bone marrow-derived MSCs; however, the total cell pooling method is technically simpler and more cost effective than the standard isolation method.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
  10. Al-Salihi KA
    Med J Malaysia, 2004 May;59 Suppl B:200-1.
    PMID: 15468887
    In the present study, natural coral of porites species was used as scaffold combined with in vitro expanded bone marrow stem cell derived osteoblasts (BMSC-DO), to develop a tissue-engineered bone graft in a rat model. Coral was molded into the shape of rat mandible seeded with 5x10(6) /ml BMSC-DO subsequently implanted subcutaneously in the back of 5 week Sprague dawely rats for 3 months. Coral alone was implanted as a control. The implants were harvest and processed for gross inspection and histological observations. The results showed that newly bone grafts were successfully formed coral seeded with cells group showed smooth highly vascularized like bone tissue. Histological sections revealed mature bone formation and lots of blood vessel, the bone formation occurred in the manner resemble intramembraneous bone formation. This study demonstrates that coral can be use as a suitable scaffold material for delivering bone marrow mesenchymal stem cells in tissue engineering.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
  11. Karunanithi P, Murali MR, Samuel S, Raghavendran HRB, Abbas AA, Kamarul T
    Carbohydr Polym, 2016 08 20;147:294-303.
    PMID: 27178935 DOI: 10.1016/j.carbpol.2016.03.102
    Presence of sulfated polysaccharides like heparan sulphate has often been implicated in the regulation of chondrogenesis. However, recently there has been a plethora of interest in the use of non-animal extracted analogs of heparan sulphate. Here we remodeled alginate (1.5%) by incorporating fucoidan (0.5%), a natural sulphated polysaccharide extracted from seaweeds to form a composite hydrogel (Al-Fu), capable of enhancing chondrogenesis of human mesenchymal stromal cells (hMSCs). We confirmed the efficiency of fucoidan incorporation by FTIR and EDX analysis. Further, its ability to support hMSC attachment and chondrogenic differentiation was confirmed by SEM, biochemical glycosaminoglycan quantification, real-time quantitative PCR and immunocytochemical analyses of chondrogenic markers Sox-9, Collagen II, Aggrecan and COMP. Effect of Al-Fu hydrogel on hMSC hypertrophy was also confirmed by the downregulation of hypertrophic genes Collagen X and Runx2. This composite scaffold can hence be used as a cartilage biomimetic biomaterial to drive hMSC chondrogenesis and for other cartilage repair based therapies.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
  12. Looi SY, Bastion MC, Leow SN, Luu CD, Hairul NMH, Ruhaslizan R, et al.
    Indian J Ophthalmol, 2022 Jan;70(1):201-209.
    PMID: 34937239 DOI: 10.4103/ijo.IJO_473_21
    Purpose: There are no effective treatments currently available for optic nerve transection injuries. Stem cell therapy represents a feasible future treatment option. This study investigated the therapeutic potential of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation in rats with optic nerve injury.

    Methods: Sprague-Dawley (SD) rats were divided into three groups: a no-treatment control group (n = 6), balanced salt solution (BSS) treatment group (n = 6), and hUC-MSCs treatment group (n = 6). Visual functions were assessed by flash visual evoked potential (fVEP) at baseline, Week 3, and Week 6 after optic nerve crush injury. Right eyes were enucleated after 6 weeks for histology.

    Results: The fVEP showed shortened latency delay and increased amplitude in the hUC-MSCs treated group compared with control and BSS groups. Higher cellular density was detected in the hUC-MSC treated group compared with the BSS and control groups. Co-localized expression of STEM 121 and anti-S100B antibody was observed in areas of higher nuclear density, both in the central and peripheral regions.

    Conclusion: Peribulbar transplantation of hUC-MSCs demonstrated cellular integration that can potentially preserve the optic nerve function with a significant shorter latency delay in fVEP and higher nuclear density on histology, and immunohistochemical studies observed cell migration particularly to the peripheral regions of the optic nerve.

    Matched MeSH terms: Mesenchymal Stromal Cells*
  13. Wu X, Zhang S, Lai J, Lu H, Sun Y, Guan W
    Exp Clin Transplant, 2020 12;18(7):823-831.
    PMID: 33349209 DOI: 10.6002/ect.2020.0108
    OBJECTIVES: Liver fibrosis is inevitable in the healing process of liver injury. Liver fibrosis will develop into liver cirrhosis unless the damaging factors are removed. This study investigated the potential therapy of Bama pig adipose-derived mesenchymal stem cells in a carbon tetrachloride-induced liver fibrosis Institute of Cancer Research strain mice model.

    MATERIALS AND METHODS: Adipose-derived mesenchymal stem cells were injected intravenously into the tails of mice of the Institute of Cancer Research strain that had been treated with carbon tetrachloride for 4 weeks. Survival rate, migration, and proliferation of adipose-derived mesenchymal stem cells in the liver were observed by histochemistry, fluorescent labeling, and serological detection.

    RESULTS: At 1, 2, and 3 weeks after adipose-derived mesenchymal stem cell injection, liver fibrosis was significantly ameliorated. The injected adipose-derived mesenchymal stem cells had hepatic differentiation potential in vivo, and the survival rate of adipose-derived mesenchymal stem cells declined over time.

    CONCLUSIONS: The findings in this study confirmed that adipose-derived mesenchymal stem cells derived from the Bama pig can be used in the treatment of liver fibrosis, and the grafted adipose-derived mesenchy-mal stem cells can migrate, survive, and differentiate into hepatic cells in vivo.

    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism; Mesenchymal Stromal Cells/physiology*
  14. Kardia E, Zakaria N, Sarmiza Abdul Halim NS, Widera D, Yahaya BH
    Regen Med, 2017 03;12(2):203-216.
    PMID: 28244823 DOI: 10.2217/rme-2016-0112
    The therapeutic use of mesenchymal stromal cells (MSCs) represents a promising alternative clinical strategy for treating acute and chronic lung disorders. Several preclinical reports demonstrated that MSCs can secrete multiple paracrine factors and that their immunomodulatory properties can support endothelial and epithelial regeneration, modulate the inflammatory cascade and protect lungs from damage. The effects of MSC transplantation into patients suffering from lung diseases should be fully evaluated through careful assessment of safety and associated risks, which is a prerequisite for translation of preclinical research into clinical practice. In this article, we summarize the current status of preclinical research and review initial MSC-based clinical trials for treating lung injuries and lung disorders.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
  15. Nam HY, Pingguan-Murphy B, Amir Abbas A, Mahmood Merican A, Kamarul T
    Biomech Model Mechanobiol, 2015 Jun;14(3):649-63.
    PMID: 25351891 DOI: 10.1007/s10237-014-0628-y
    It has been previously demonstrated that mechanical stimuli are important for multipotent human bone marrow-derived mesenchymal stromal cells (hMSCs) to maintain good tissue homeostasis and even to enhance tissue repair processes. In tendons, this is achieved by promoting the cellular proliferation and tenogenic expression/differentiation. The present study was conducted to determine the optimal loading conditions needed to achieve the best proliferation rates and tenogenic differentiation potential. The effects of mechanical uniaxial stretching using different rates and strains were performed on hMSCs cultured in vitro. hMSCs were subjected to cyclical uniaxial stretching of 4, 8 or 12 % strain at 0.5 or 1 Hz for 6, 24, 48 or 72 h. Cell proliferation was analyzed using alamarBlue[Formula: see text] assay, while hMSCs differentiation was analyzed using total collagen assay and specific tenogenic gene expression markers (type I collagen, type III collagen, decorin, tenascin-C, scleraxis and tenomodulin). Our results demonstrate that the highest cell proliferation is observed when 4 % strain [Formula: see text] 1 Hz was applied. However, at 8 % strain [Formula: see text] 1 Hz loading, collagen production and the tenogenic gene expression were highest. Increasing strain or rates thereafter did not demonstrate any significant increase in both cell proliferation and tenogenic differentiation. In conclusion, our results suggest that 4 % [Formula: see text] 1 Hz cyclic uniaxial loading increases cell proliferation, but higher strains are required for superior tenogenic expressions. This study suggests that selected loading regimes will stimulate tenogenesis of hMSCs.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
  16. Al Faqeh H, Nor Hamdan BM, Chen HC, Aminuddin BS, Ruszymah BH
    Exp Gerontol, 2012 Jun;47(6):458-64.
    PMID: 22759409 DOI: 10.1016/j.exger.2012.03.018
    In recent years, the use of bone marrow mesenchymal stem cell (BMSC) implantation has provided an alternative treatment for osteoarthritis. The objective of this study is to determine whether or not an intra-articular injection of a single dose of autologous chondrogenic induced BMSC could retard the progressive destruction of cartilage in a surgically induced osteoarthritis in sheep. Sheep BMSCs were isolated and divided into two groups. One group was cultured in chondrogenic media containing (Ham's F12:DMEM, 1:1) FD+1% FBS+5 ng/ml TGFβ3+50 ng/ml IGF-1 (CM), and the other group was cultured in the basal media, FD+10% FBS (BM). The procedure for surgically induced osteoarthritis was performed on the donor sheep 6 weeks prior to intra-articular injection into the knee joint of a single dose of BMSC from either group, suspended in 5 ml FD at density of 2 million cells/ml. The control groups were injected with basal media, without cells. Six weeks after injection, gross evidence of retardation of cartilage destruction was seen in the osteoarthritic knee joints treated with CM as well as BM. No significant ICRS (International Cartilage Repair Society) scoring was detected between the two groups with cells. However macroscopically, meniscus repair was observed in the knee joint treated with CM. Severe osteoarthritis and meniscal injury was observed in the control group. Interestingly, histologically the CM group demonstrated good cartilage histoarchitecture, thickness and quality, comparable to normal knee joint cartilage. As a conclusion, intra-articular injection of a single dose of BMSC either chondrogenically induced or not, could retard the progression of osteoarthritis (OA) in a sheep model, but the induced cells indicated better results especially in meniscus regeneration.
    Study site: Universiti Kebangsaan Malaysia, Kuala Lumpur
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology
  17. Abdul Rahman R, Mohamad Sukri N, Md Nazir N, Ahmad Radzi MA, Zulkifly AH, Che Ahmad A, et al.
    Tissue Cell, 2015 Aug;47(4):420-30.
    PMID: 26100682 DOI: 10.1016/j.tice.2015.06.001
    Articular cartilage is well known for its simple uniqueness of avascular and aneural structure that has limited capacity to heal itself when injured. The use of three dimensional construct in tissue engineering holds great potential in regenerating cartilage defects. This study evaluated the in vitro cartilaginous tissue formation using rabbit's bone marrow mesenchymal stem cells (BMSCs)-seeded onto poly(lactic-co-glycolic acid) PLGA/fibrin and PLGA scaffolds. The in vitro cartilaginous engineered constructs were evaluated by gross inspection, histology, cell proliferation, gene expression and sulphated glycosaminoglycan (sGAG) production at week 1, 2 and 3. After 3 weeks of culture, the PLGA/fibrin construct demonstrated gross features similar to the native tissue with smooth, firm and glistening appearance, superior histoarchitectural and better cartilaginous extracellular matrix compound in concert with the positive glycosaminoglycan accumulation on Alcian blue. Significantly higher cell proliferation in PLGA/fibrin construct was noted at day-7, day-14 and day-21 (p<0.05 respectively). Both constructs expressed the accumulation of collagen type II, collagen type IX, aggrecan and sox9, showed down-regulation of collagen type I as well as produced relative sGAG content with PLGA/fibrin construct exhibited better gene expression in all profiles and showed significantly higher relative sGAG content at each time point (p<0.05). This study suggested that with optimum in vitro manipulation, PLGA/fibrin when seeded with pluripotent non-committed BMSCs has the capability to differentiate into chondrogenic lineage and may serve as a prospective construct to be developed as functional tissue engineered cartilage.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism*; Mesenchymal Stromal Cells/chemistry
  18. Zulkifli A, Ahmad RE, Krishnan S, Kong P, Nam HY, Kamarul T
    Tissue Cell, 2023 Jun;82:102075.
    PMID: 37004269 DOI: 10.1016/j.tice.2023.102075
    Tendon injuries account up to 50% of all musculoskeletal problems and remains a challenge to treat owing to the poor intrinsic reparative ability of tendon tissues. The natural course of tendon healing is very slow and often leads to fibrosis and disorganized tissues with inferior biomechanical properties. Mesenchymal stem cells (MSC) therapy is a promising alternative strategy to augment tendon repair due to its proliferative and multilineage differentiation potential. Hypoxic conditioning of MSC have been shown to enhance their tenogenic differentiation capacity. However, the mechanistic pathway by which this is achieved is yet to be fully defined. A key factor involved in this pathway is hypoxia-inducible factor-1-alpha (HIF-1α). This review aims to discuss the principal mechanism underlying the enhancement of MSC tenogenic differentiation by hypoxic conditioning, particularly the central role of HIF-1α in mediating activation of tenogenic pathways in the MSC. We focus on the interaction between HIF-1α with fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta 1 (TGF-β1) in regulating MSC tenogenic differentiation pathways in hypoxic conditions. Strategies to promote stabilization of HIF-1α either through direct manipulation of oxygen tension or the use of hypoxia mimicking agents are therefore beneficial in increasing the efficacy of MSC therapy for tendon repair.
    Matched MeSH terms: Mesenchymal Stromal Cells*
  19. Krishnamurithy G, Mohan S, Yahya NA, Mansor A, Murali MR, Raghavendran HRB, et al.
    PLoS One, 2019;14(3):e0214212.
    PMID: 30917166 DOI: 10.1371/journal.pone.0214212
    It has been demonstrated that nanocrystalline forsterite powder synthesised using urea as a fuel in sol-gel combustion method had produced a pure forsterite (FU) and possessed superior bioactive characteristics such as bone apatite formation and antibacterial properties. In the present study, 3D-scaffold was fabricated using nanocrystalline forsterite powder in polymer sponge method. The FU scaffold was used in investigating the physicochemical, biomechanics, cell attachment, in vitro biocompatibility and osteogenic differentiation properties. For physicochemical characterisation, Fourier-transform infrared spectroscopy (FTIR), Energy dispersive X-ray (EDX), X-ray diffraction (XRD), Raman spectroscopy, X-ray photoemission spectrometer (XPS) and Brunauer-Emmett-Teller (BET) were used. FTIR, EDX, XRD peaks and Raman spectroscopy demonstrated correlating to FU. The XPS confirmed the surface chemistry associating to FU. The BET revealed FU scaffold surface area of 12.67 m2/g and total pore size of 0.03 cm3/g. Compressive strength of the FU scaffold was found to be 27.18 ± 13.4 MPa. The human bone marrow derived mesenchymal stromal cells (hBMSCs) characterisation prior to perform seeding on FU scaffold verified the stromal cell phenotypic and lineage commitments. SEM, confocal images and presto blue viability assay suggested good cell attachment and proliferation of hBMSCs on FU scaffold and comparable to a commercial bone substitutes (cBS). Osteogenic proteins and gene expression from day 7 onward indicated FU scaffold had a significant osteogenic potential (p<0.05), when compared with day 1 as well as between FU and cBS. These findings suggest that FU scaffold has a greater potential for use in orthopaedic and/or orthodontic applications.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology; Mesenchymal Stromal Cells/metabolism*
  20. Ramasamy R, Tong CK, Seow HF, Vidyadaran S, Dazzi F
    Cell Immunol, 2008 Feb;251(2):131-6.
    PMID: 18502411 DOI: 10.1016/j.cellimm.2008.04.009
    Mesenchymal stem cells (MSC) are non-haematopoietic stem cells that are capable of differentiating into tissues of mesodermal origin. MSC play an important role in supporting the development of fetal and adult haematopoiesis. More recently, MSC have also been found to exhibit inhibitory effect on T cell responses. However, there is little information on the mechanism of this immunosuppression and our study addresses this issue by targeting T cell functions at various level of immune responses. We have generated MSC from human adult bone marrow (BM) and investigated their immunoregulatory function at different phases of T cell responses. MSC showed the ability to inhibit mitogen (CD3/CD28 microbeads)-activated T cell proliferation in a dose-dependent manner. In order to evaluate the specificity of this immunosuppression, the proliferation of CD4(+) and CD8(+) cells were measured. MSC equally inhibit CD4(+) and CD8(+) subpopulations of T cells in response to PHA stimulation. However, the antiproliferative effect of MSC is not due to the inhibition of T cell activation. The expression of early activation markers of T cells, namely CD25 and CD69 were not significantly altered by MSC at 24, 48 and 72h. Furthermore, the immunosuppressive effect of MSC mainly targets T cell proliferation rather than their effector function since cytotoxicity of T cells is not affected. This work demonstrates that the immunosuppressive effect of MSC is exclusively a consequence of an anti-proliferative activity, which targets T cells of different subpopulations. For this reason, they have the potential to be exploited in the control of unwanted immune responses such as graft versus host disease (GVHD) and autoimmunity.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology; Mesenchymal Stromal Cells/immunology*
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