Displaying publications 41 - 60 of 88 in total

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  1. Puvaneswary S, Balaji Raghavendran HR, Ibrahim NS, Murali MR, Merican AM, Kamarul T
    Int J Med Sci, 2013;10(12):1608-14.
    PMID: 24151432 DOI: 10.7150/ijms.6496
    The objective of this study was to compare the morphological and chemical composition of bone graft (BG) and coral graft (CG) as well as their osteogenic differentiation potential using rabbit mesenchymal stem cells (rMSCs) in vitro. SEM analysis of BG and CG revealed that the pores in these grafts were interconnected, and their micro-CT confirmed pore sizes in the range of 107-315 µm and 103-514 µm with a total porosity of 92% and 94%, respectively. EDS analysis indicated that the level of calcium in CG was relatively higher than that in BG. FTIR of BG and CG confirmed the presence of functional groups corresponding to carbonyl, aromatic, alkyl, and alkane groups. XRD results revealed that the phase content of the inorganic layer comprised highly crystalline form of calcium carbonate and carbon. Atomic force microscopy analysis showed CG had better surface roughness compared to BG. In addition, significantly higher levels of osteogenic differentiation markers, namely, alkaline phosphatase (ALP), Osteocalcin (OC) levels, and Osteonectin and Runx2, Integrin gene expression were detected in the CG cultures, when compared with those in the BG cultures. In conclusion, our results demonstrate that the osteogenic differentiation of rMSCs is relatively superior in coral graft than in bone graft culture system.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism
  2. Mok PL, Cheong SK, Leong CF, Chua KH, Ainoon O
    Tissue Cell, 2012 Aug;44(4):249-56.
    PMID: 22560724 DOI: 10.1016/j.tice.2012.04.002
    Mesenchymal stromal cells (MSC) are an attractive cell-targeting vehicle for gene delivery. MIDGE (an acronym for Minimalistic, Immunologically Defined Gene Expression) construct is relatively safer than the viral or plasmid expression system as the detrimental eukaryotic and prokaryotic gene and sequences have been eliminated. The objective of this study was to test the ability of the human MSC (hMSC) to deliver the erythropoietin (EPO) gene in a nude mice model following nucleofection using a MIDGE construct. hMSC nucleofected with MIDGE encoding the EPO gene was injected subcutaneously in Matrigel at the dorsal flank of nude mice. Subcutaneous implantation of nucleofected hMSC resulted in increased hemoglobin level with presence of human EPO in the peripheral blood of the injected nude mice in the first two weeks post-implantation compared with the control groups. The basal layer of the hair shaft in the dermal layer was found to be significantly positive for immunohistochemical staining of a human EPO antibody. However, only a few basal layers of the hair shaft were found to be positively stained for CD105. In conclusion, hMSC harboring MIDGE-EPO could deliver and transiently express the EPO gene in the nude mice model. These cells could be localized to the hair follicle and secreted EPO protein might have possible role in hair regeneration.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism
  3. Govindasamy V, Ronald VS, Abdullah AN, Ganesan Nathan KR, Aziz ZA, Abdullah M, et al.
    Cytotherapy, 2011 Nov;13(10):1221-33.
    PMID: 21929379 DOI: 10.3109/14653249.2011.602337
    BACKGROUND AIMS. Dental pulp stromal cells (DPSC) are considered to be a promising source of stem cells in the field of regenerative therapy. However, the usage of DPSC in transplantation requires large-scale expansion to cater for the need for clinical quantity without compromising current good manufacturing practice (cGMP). Existing protocols for cell culturing make use of fetal bovine serum (FBS) as a nutritional supplement. Unfortunately, FBS is an undesirable additive to cells because it carries the risk of transmitting viral and prion diseases. Therefore, the present study was undertaken to examine the efficacy of human platelet lysate (HPL) as a substitute for FBS in a large-scale set-up. METHODS. We expanded the DPSC in Dulbecco's modified Eagle's medium-knock-out (DMEM-KO) with either 10% FBS or 10% HPL, and studied the characteristics of DPSC at pre- (T25 culture flask) and post- (5-STACK chamber) large-scale expansion in terms of their identity, quality, functionality, molecular signatures and cytogenetic stability. RESULTS. In both pre- and post-large-scale expansion, DPSC expanded in HPL showed extensive proliferation of cells (c. 2-fold) compared with FBS; the purity, immune phenotype, colony-forming unit potential and differentiation were comparable. Furthermore, to understand the gene expression profiling, the transcriptomes and cytogenetics of DPSC expanded under HPL and FBS were compared, revealing similar expression profiles. CONCLUSIONS. We present a highly economized expansion of DPSC in HPL, yielding double the amount of cells while retaining their basic characteristics during a shorter time period under cGMP conditions, making it suitable for therapeutic applications.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism*
  4. Munawer NH, Md Zin R, Md Ali SA, Muhammad R, Ali J, Das S
    Biomed J, 2012 Nov-Dec;35(6):486-92.
    PMID: 23442362 DOI: 10.4103/2319-4170.104414
    Fibroadenomas (FA) are common while phyllodes tumors (PT) are rare and both tumors are composed of epithelial and stromal components. We evaluated the expression status of ER, Bc12, p53, and MIB-1 protein in these tumors.
    Matched MeSH terms: Stromal Cells/metabolism
  5. 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*
  6. Rafieerad A, Yan W, Sequiera GL, Sareen N, Abu-El-Rub E, Moudgil M, et al.
    Adv Healthc Mater, 2019 08;8(16):e1900569.
    PMID: 31265217 DOI: 10.1002/adhm.201900569
    Inflammation is tightly linked to tissue injury. In regenerative medicine, immune activation plays a key role in rejection of transplanted stem cells and reduces the efficacy of stem cell therapies. Next-generation smart biomaterials are reported to possess multiple biologic properties for tissue repair. Here, the first use of 0D titanium carbide (Ti3 C2 ) MXene quantum dots (MQDs) for immunomodulation is presented with the goal of enhancing material-based tissue repair after injury. MQDs possess intrinsic immunomodulatory properties and selectively reduce activation of human CD4+ IFN-γ+ T-lymphocytes (control 87.1 ± 2.0%, MQDs 68.3 ± 5.4%) while promoting expansion of immunosuppressive CD4+ CD25+ FoxP3+ regulatory T-cells (control 5.5 ± 0.7%, MQDs 8.5 ± 0.8%) in a stimulated lymphocyte population. Furthermore, MQDs are biocompatible with bone marrow-derived mesenchymal stem cells and induced pluripotent stem cell-derived fibroblasts. Finally, Ti3 C2 MQDs are incorporated into a chitosan-based hydrogel to create a 3D platform with enhanced physicochemical properties for stem cell delivery and tissue repair. This composite hydrogel demonstrates increased conductivity while maintaining injectability and thermosensitivity. These findings suggest that this new class of biomaterials may help bridge the translational gap in material and stem cell-based therapies for tissue repair and treatment of inflammatory and degenerative diseases.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism
  7. Alsaeedi HA, Koh AE, Lam C, Rashid MBA, Harun MHN, Saleh MFBM, et al.
    J. Photochem. Photobiol. B, Biol., 2019 Sep;198:111561.
    PMID: 31352000 DOI: 10.1016/j.jphotobiol.2019.111561
    Blindness and vision loss contribute to irreversible retinal degeneration, and cellular therapy for retinal cell replacement has the potential to treat individuals who have lost light sensitive photoreceptors in the retina. Retinal cells are well characterized in function, and are a subject of interest in cellular replacement therapy of photoreceptors and the retinal pigment epithelium. However, retinal cell transplantation is limited by various factors, including the choice of potential stem cell source that can show variability in plasticity as well as host tissue integration. Dental pulp is one such source that contains an abundance of stem cells. In this study we used dental pulp-derived mesenchymal stem cells (DPSCs) to mitigate sodium iodate (NaIO3) insult in a rat model of retinal degeneration. Sprague-Dawley rats were first given an intravitreal injection of 3 × 105 DPSCs as well as a single systemic administration of NaIO3 (40 mg/kg). Electroretinography (ERG) was performed for the next two months and was followed-up by histological analysis. The ERG recordings showed protection of DPSC-treated retinas within 4 weeks, which was statistically significant (* P ≤ .05) compared to the control. Retinal thickness of the control was also found to be thinner (*** P ≤ .001). The DPSCs were found integrated in the photoreceptor layer through immunohistochemical staining. Our findings showed that DPSCs have the potential to moderate retinal degeneration. In conclusion, DPSCs are a potential source of stem cells in the field of eye stem cell therapy due to its protective effects against retinal degeneration.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism
  8. Akhir HM, Teoh PL
    Biosci Rep, 2020 12 23;40(12).
    PMID: 33245097 DOI: 10.1042/BSR20201325
    Collagen has been widely shown to promote osteogenesis of bone marrow mesenchymal stromal cells (BM-MSCs). Due to the invasive procedure of obtaining BM-MSCs, MSCs from other tissues have emerged as a promising alternative for regenerative therapy. MSCs originated from different sources, exhibiting different differentiation potentials. Therefore, the applicability of collagen type I (COL), combining with amniotic membrane (AM)-MSCs was examined through proliferation and differentiation assays together with the expression of surface markers and genes associated with stemness and differentiation under basal or induction conditions. No increase in cell growth was observed because AM-MSCs might be directed toward spontaneous osteogenesis. This was evidenced by the calcium deposition and elevated expression of osteogenic genes when AM-MSCs were cultured in collagen plate with basal media. Under the osteogenic condition, reciprocal expression of OCN and CEBPA suggested a shift toward adipogenesis. Surprisingly, adipogenic genes were not elevated upon adipogenic induction, although oil droplets deposition was observed. In conclusion, our findings demonstrated that collagen causes spontaneous osteogenesis in AM-MSCs. However, the presence of exogenous inductors could shift the direction of adipo-osteogenic gene regulatory network modulated by collagen.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism
  9. Muhammad SA, Nordin N, Hussin P, Mehat MZ, Abu Kasim NH, Fakurazi S
    PLoS One, 2020;15(9):e0238449.
    PMID: 32886713 DOI: 10.1371/journal.pone.0238449
    Treatment of osteoarthritis (OA) is still a major clinical challenge due to the limited inherent healing capacity of cartilage. Recent studies utilising stem cells suggest that the therapeutic benefits of these cells are mediated through the paracrine mechanism of bioactive molecules. The present study evaluates the regenerative effect of stem cells from human exfoliated deciduous teeth (SHED) conditioned medium (CM) on OA chondrocytes. The CM was collected after the SHED were cultured in serum-free medium (SFM) for 48 or 72 h and the cells were characterised by the expression of MSC and pluripotency markers. Chondrocytes were stimulated with interleukin-1β and treated with the CM. Subsequently, the expression of aggrecan, collagen type 2 (COL 2), matrix metalloproteinase-13 (MMP-13), nuclear factor-kB (NF-kB) and the level of inflammatory and anti-inflammatory markers were evaluated. SHED expressed mesenchymal stromal cell surface proteins but were negative for haematopoietic markers. SHED also showed protein expression of NANOG, OCT4 and SOX2 with differential subcellular localisation. Treatment of OA chondrocytes with CM enhanced anti-inflammation compared to control cells treated with SFM. Furthermore, the expression of MMP-13 and NF-kB was significantly downregulated in stimulated chondrocytes incubated in CM. The study also revealed that CM increased the expression of aggrecan and COL 2 in OA chondrocytes compared to SFM control. Both CM regenerate extracellular matrix proteins and mitigate increased MMP-13 expression through inhibition of NF-kB in OA chondrocytes due to the presence of bioactive molecules. The study underscores the potential of CM for OA treatment.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism
  10. Hama M, Ishima Y, Chuang VTG, Ando H, Shimizu T, Ishida T
    ACS Appl Mater Interfaces, 2021 May 05;13(17):19736-19744.
    PMID: 33881292 DOI: 10.1021/acsami.1c03065
    Abraxane, an albumin-bound paclitaxel nanoparticle formulation, is superior to conventional paclitaxel preparations because it has better efficacy against unresectable pancreatic cancer. Previous reports suggest that this better efficacy of Abraxane than conventional paclitaxel preparation is probably due to its transport through Gp60, an albumin receptor on the surface of vascular endothelial cells. The increased tumor accumulation of Abraxane is also caused by the secreted protein acid and rich in cysteine in the tumor stroma. However, the uptake mechanism of Abraxane remains poorly understood. In this study, we demonstrated that the delivery of Abraxane occurred via different receptor pathways from that of endogenous albumin. Our results showed that the uptake of endogenous albumin was inhibited by a Gp60 pathway inhibitor in the process of endocytosis through endothelial cells or tumor cells. In contrast, the uptake of Abraxane-derived HSA was less affected by the Gp60 pathway inhibitor but significantly reduced by denatured albumin receptor inhibitors. In conclusion, these data indicate that Abraxane-derived HSA was taken up into endothelial cells or tumor cells by a mechanism different from normal endogenous albumin. These new data on distinct cellular transport pathways of denatured albumin via gp family proteins different from those of innate albumin shed light on the mechanisms of tumor delivery and antitumor activity of Abraxane and provide new scientific rationale for the development of a novel albumin drug delivery strategy via a denatured albumin receptor.
    Matched MeSH terms: Stromal Cells/metabolism
  11. Fonseka M, Ramasamy R, Tan BC, Seow HF
    Cell Biol Int, 2012 Sep;36(9):793-801.
    PMID: 22335239 DOI: 10.1042/CBI20110595
    hUCB-MSC (human umbilical cord blood-derived mesenchymal stem cells) offer an attractive alternative to bone marrow-derived MSC for cell-based therapy by being less invasive a source of biological material. We have evaluated the effect of hUCB-MSC on the proliferation of K562 (an erythromyeloblastoid cell line) and the cytokine secretion pattern of hUCB-MSC. Co-culturing of hUCB-MSC and K562 resulted in inhibition of proliferation of K562 in a dose-dependent manner. However, the anti-proliferative effect was reduced in transwells, suggesting the importance of direct cell-to-cell contact. hUCB-MSC inhibited proliferation of K562, arresting them in the G0 /G1 phase. NO (nitric oxide) was not involved in the hUCB-MSC-mediated tumour suppression. The presence of IL-6 (interleukin 6) and IL-8 were obvious in the hUCB-MSC conditioned media, but no significant increase was found in 29 other cytokines. Th1 cytokines, IFNα (interferon α), Th2 cytokine IL-4 and Th17 cytokine, IL-17 were not secreted by hUCB-MSC. There was an increase in the number of hUCB-MSC expressing the latent membrane-bound form of TGFβ1 co-cultured with K562. The anti-proliferative effect of hUCB-MSC was due to arrest of the growth of K562 in the G0 /G1 phase. The mechanisms underlying increased IL-6 and IL-8 secretion and LAP (latency-associated peptide; TGFβ1) by hUCB-MSC remains unknown.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism*
  12. Lim J, Razi ZR, Law J, Nawi AM, Idrus RB, Ng MH
    Cytotherapy, 2016 12;18(12):1493-1502.
    PMID: 27727016 DOI: 10.1016/j.jcyt.2016.08.003
    BACKGROUND AIMS: Human Wharton's jelly-derived mesenchymal stromal cells (hWJMSCs) are possibly the most suitable allogeneic cell source for stromal cell therapy and tissue engineering applications because of their hypo-immunogenic and non-tumorigenic properties, easy availability and minimal ethical concerns. Furthermore, hWJMSCs possess unique properties of both adult mesenchymal stromal cells and embryonic stromal cells. The human umbilical cord (UC) is approximately 50-60 cm long and the existing studies in the literature have not provided information on which segment of the UC was studied. In this study, hWJMSCs derived from three anatomical segments of the UC are compared.

    METHODS: Three segments of the whole UC, each 3 cm in length, were identified anatomically as the maternal, middle and fetal segments. The hWJMSCs from the different segments were analyzed via trypan blue exclusion assay to determine the growth kinetics and cell viability, flow cytometry for immunophenotyping and immunofluorescence and reverse transcriptase polymerase chain reaction (RT-PCR) for expression of stromal cell transcriptional factors. Furthermore, the trilineage differentiation potential (osteogenic, adipogenic and chondrogenic) of these cells was also assessed.

    RESULTS: hWJMSCs isolated from the maternal and fetal segments displayed greater viability and possessed a significantly higher proliferation rate compared with cells from the middle segment. Immunophenotyping revealed that hWJMSCs derived from all three segments expressed the MSC markers CD105, CD73, CD90, CD44, CD13 and CD29, as well as HLA-ABC and HLA-DR, but were negative for hematopoietic markers CD14, CD34 and CD45. Analysis of the embryonic markers showed that all three segments expressed Nanog and Oct 3/4, but only the maternal and fetal segments expressed SSEA 4 and TRA-160. Cells from all three segments were able to differentiate into chondrogenic, osteogenic and adipogenic lineages with the middle segments showing much lower differentiation potential compared with the other two segments.

    CONCLUSIONS: hWJMSCs derived from the maternal and fetal segments of the UC are a good source of MSCs compared with cells from the middle segment because of their higher proliferation rate and viability. Fetal and maternal segments are the preferred cell source for bone regeneration.

    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism
  13. Nam HY, Balaji Raghavendran HR, Pingguan-Murphy B, Abbas AA, Merican AM, Kamarul T
    PLoS One, 2017;12(6):e0178117.
    PMID: 28654695 DOI: 10.1371/journal.pone.0178117
    The role for mechanical stimulation in the control of cell fate has been previously proposed, suggesting that there may be a role of mechanical conditioning in directing mesenchymal stromal cells (MSCs) towards specific lineage for tissue engineering applications. Although previous studies have reported that calcium signalling is involved in regulating many cellular processes in many cell types, its role in managing cellular responses to tensile loading (mechanotransduction) of MSCs has not been fully elucidated. In order to establish this, we disrupted calcium signalling by blocking stretch-activated calcium channel (SACC) in human MSCs (hMSCs) in vitro. Passaged-2 hMSCs were exposed to cyclic tensile loading (1 Hz + 8% for 6, 24, 48, and 72 hours) in the presence of the SACC blocker, gadolinium. Analyses include image observations of immunochemistry and immunofluorescence staining from extracellular matrix (ECM) production, and measuring related tenogenic and apoptosis gene marker expression. Uniaxial tensile loading increased the expression of tenogenic markers and ECM production. However, exposure to strain in the presence of 20 μM gadolinium reduced the induction of almost all tenogenic markers and ECM staining, suggesting that SACC acts as a mechanosensor in strain-induced hMSC tenogenic differentiation process. Although cell death was observed in prolonged stretching, it did not appear to be apoptosis mediated. In conclusion, the knowledge gained in this study by elucidating the role of calcium in MSC mechanotransduction processes, and that in prolonged stretching results in non-apoptosis mediated cell death may be potential useful for regenerative medicine applications.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism
  14. 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.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism
  15. Subramani B, Subbannagounder S, Ramanathanpullai C, Palanivel S, Ramasamy R
    Exp Biol Med (Maywood), 2017 03;242(6):645-656.
    PMID: 28092181 DOI: 10.1177/1535370216688568
    Redox homeostasis plays a crucial role in the regulation of self-renewal and differentiation of stem cells. However, the behavioral actions of mesenchymal stem cells in redox imbalance state remain elusive. In the present study, the effect of redox imbalance that was induced by either hydrogen peroxide (H2O2) or ascorbic acid on human cardiac-resident (hC-MSCs) and non-resident (umbilical cord) mesenchymal stem cells (hUC-MSCs) was evaluated. Both cells were sensitive and responsive when exposed to either H2O2 or ascorbic acid at a concentration of 400 µmol/L. Ascorbic acid pre-treated cells remarkably ameliorated the reactive oxygen species level when treated with H2O2. The endogenous antioxidative enzyme gene (Sod1, Sod2, TRXR1 and Gpx1) expressions were escalated in both MSCs in response to reactive oxygen species elevation. In contrast, ascorbic acid pre-treated hUC-MSCs attenuated considerable anti-oxidative gene (TRXR1 and Gpx1) expressions, but not the hC-MSCs. Similarly, the cardiogenic gene (Nkx 2.5, Gata4, Mlc2a and β-MHC) and ion-channel gene ( IKDR, IKCa, Ito and INa.TTX) expressions were significantly increased in both MSCs on the oxidative state. On the contrary, reduced environment could not alter the ion-channel gene expression and negatively regulated the cardiogenic gene expressions except for troponin-1 in both cells. In conclusion, redox imbalance potently alters the cardiac-resident and non-resident MSCs stemness, cardiogenic, and ion-channel gene expressions. In comparison with cardiac-resident MSC, non-resident umbilical cord-MSC has great potential to tolerate the redox imbalance and positively respond to cardiac regeneration. Impact statement Human mesenchymal stem cells (h-MSCs) are highly promising candidates for tissue repair in cardiovascular diseases. However, the retention of cells in the infarcted area has been a major challenge due to its poor viability and/or low survival rate after transplantation. The regenerative potential of mesenchymal stem cells (MSCs) repudiate and enter into premature senescence via oxidative stress. Thus, various strategies have been attempted to improve the MSC survival in 'toxic' conditions. Similarly, we investigated the response of cardiac resident MSC (hC-MSCs) and non-resident MSCs against the oxidative stress induced by H2O2. Supplementation of ascorbic acid (AA) into MSCs culture profoundly rescued the stem cells from oxidative stress induced by H2O2. Our data showed that the pre-treatment of AA is able to inhibit the cell death and thus preserving the viability and differentiation potential of MSCs.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism
  16. Siow KS, Abdul Rahman AS, Ng PY, Majlis BY
    Mater Sci Eng C Mater Biol Appl, 2020 Feb;107:110225.
    PMID: 31761201 DOI: 10.1016/j.msec.2019.110225
    Role of sulfur (S) and nitrogen (N) groups in promoting cell adhesion or commonly known as biocompatibility, is well established, but their role in reducing bacterial attachment and growth is less explored or not well-understood. Natural sulfur-based compounds, i.e. sulfide, sulfoxide and sulfinic groups, have shown to inhibit bacterial adhesion and biofilm formation. Hence, we mimicked these surfaces by plasma polymerizing thiophene (ppT) and air-plasma treating this ppT to achieve coatings with S of similar oxidation states as natural compounds (ppT-air). In addition, the effects of these N and S groups from ppT-air were also compared with the biocompatible amine-amide from n-heptylamine plasma polymer. Crystal violet assay and live and dead fluorescence staining of E. coli and S. aureus showed that all the N and S coated surfaces generated, including ppHA, ppT and ppT-air, produced similarly potent, growth reduction of both bacteria by approximately 65% at 72 h compared to untreated glass control. The ability of osteogenic differentiation in Wharton's jelly mesenchymal stem cells (WJ-MSCs) were also used to test the cell biocompatibility of these surfaces. Alkaline phosphatase assay and scanning electron microscopy imaging of these WJ-MSCs growths indicated that ppHA, and ppT-air were cell-friendly surfaces, with ppHA showing the highest osteogenic activity. In summary, the N and S containing surfaces could reduce bacteria growth while promoting mammalian cell growth, thus serve as potential candidate surfaces to be explored further for biomaterial applications.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism
  17. Venugopal C, K S, Rai KS, Pinnelli VB, Kutty BM, Dhanushkodi A
    Curr Gene Ther, 2018;18(5):307-323.
    PMID: 30209999 DOI: 10.2174/1566523218666180913152615
    INTRODUCTION: Mesenchymal Stem Cell (MSC) therapy in recent years has gained significant attention. Though the functional outcomes following MSC therapy for neurodegenerative diseases are convincing, various mechanisms for the functional recovery are being debated. Nevertheless, recent studies convincingly demonstrated that recovery following MSC therapy could be reiterated with MSC secretome per se thereby shifting the dogma from cell therapy to cell "based" therapy. In addition to various functional proteins, stem cell secretome also includes extracellular membrane vesicles like exosomes. Exosomes which are of "Nano" size have attracted significant interest as they can pass through the bloodbrain barrier far easily than macro size cells or growth factors. Exosomes act as a cargo between cells to bring about significant alterations in target cells. As the importance of exosomes is getting unveil, it is imperial to carry out a comprehensive study to evaluate the neuroprotective potential of exosomes as compared to conventional co-culture or total condition medium treatments.

    OBJECTIVE: Thus, the present study is designed to compare the neuroprotective potential of MSC derived exosomes with MSC-condition medium or neuron-MSC-co-culture system against kainic acid induced excitotoxicity in in vitro condition. The study also aims at comparing the neuroprotective efficacy of exosomes/condition medium/co-culture of two MSC viz., neural crest derived human Dental Pulp Stem Cells (hDPSC) and human Bone-Marrow Mesenchymal Stem Cells (hBM-MSC) to identify the appropriate MSC source for treating neurodegenerative diseases.

    RESULT: Our results demonstrated that neuroprotective efficacy of MSC-exosomes is as efficient as MSC-condition medium or neuron-MSC co-culture system and treating degenerating hippocampal neurons with all three MSC based approaches could up-regulate host's endogenous growth factor expressions and prevent apoptosis by activating cell survival PI3K-B-cell lymphoma-2 (Bcl-2) pathway.

    CONCLUSION: Thus, the current study highlights the possibilities of treating neurodegenerative diseases with "Nano" size exosomes as opposed to transplanting billions of stem cells which inherit several disadvantages.

    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism*
  18. Samuel S, Ahmad RE, Ramasamy TS, Karunanithi P, Naveen SV, Kamarul T
    Platelets, 2019;30(1):66-74.
    PMID: 29090639 DOI: 10.1080/09537104.2017.1371287
    Platelet-rich concentrate (PRC), used in conjunction with other chondroinductive growth factors, have been shown to induce chondrogenesis of human mesenchymal stromal cells (hMSC) in pellet culture. However, pellet culture systems promote cell hypertrophy and the presence of other chondroinductive growth factors in the culture media used in previous studies obscures accurate determination of the effect of platelet itself in inducing chondrogenic differentiation. Hence, this study aimed to investigate the effect of PRC alone in enhancing the chondrogenic differentiation potential of human mesenchymal stromal cells (hMSC) encapsulated in three-dimensional alginate constructs. Cells encapsulated in alginate were cultured in serum-free medium supplemented with only 15% PRC. Scanning electron microscopy was used to determine the cell morphology. Chondrogenic molecular signature of hMSCs was determined by quantitative real-time PCR and verified at protein levels via immunohistochemistry and enzyme-linked immunosorbent assay. Results showed that the cells cultured in the presence of PRC for 24 days maintained a chondrocytic phenotype and demonstrated minimal upregulation of cartilaginous extracellular matrix (ECM) marker genes (SOX9, TNC, COL2, ACAN, COMP) and reduced expression of chondrocyte hypertrophy genes (Col X, Runx2) compared to the standard chondrogenic medium (p 
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism*
  19. Ding SLS, Kumar S, Mok PL
    Int J Mol Sci, 2017 Jul 28;18(8).
    PMID: 28788088 DOI: 10.3390/ijms18081406
    The use of multipotent mesenchymal stem cells (MSCs) has been reported as promising for the treatment of numerous degenerative disorders including the eye. In retinal degenerative diseases, MSCs exhibit the potential to regenerate into retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Delivery of MSCs was found to improve retinal morphology and function and delay retinal degeneration. In this review, we revisit the therapeutic role of MSCs in the diseased eye. Furthermore, we reveal the possible cellular mechanisms and identify the associated signaling pathways of MSCs in reversing the pathological conditions of various ocular disorders such as age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and glaucoma. Current stem cell treatment can be dispensed as an independent cell treatment format or with the combination of other approaches. Hence, the improvement of the treatment strategy is largely subjected by our understanding of MSCs mechanism of action.
    Matched MeSH terms: Mesenchymal Stromal Cells/metabolism*
  20. Mamidi MK, Pal R, Mori NA, Arumugam G, Thrichelvam ST, Noor PJ, et al.
    J Cell Biochem, 2011 May;112(5):1353-63.
    PMID: 21337383 DOI: 10.1002/jcb.23052
    Among the different parameters governing the successful derivation and expansion of human embryonic stem cells (hESC), feeder layers play the most important role. Human feeders in form of human mesenchymal stromal cells (hMSCs) and human foreskin fibroblasts (HFFs) lay the foundation for eradication of animal-derived hESC culture system. In this study we explored the potential of human foreskin derived mesenchymal like stromal cells (HF-MSCs) to support self renewal and pluripotency of hESC. The MSCs isolated from human foreskin were found to be resistant to standard concentrations and duration of mitomycin-C treatment. Growth pattern, gene profiling (Oct-4, Nanog, Sox-2, Rex-1), cytoskeletal protein expression (vimentin, nestin) and tri-lineage differentiation potential into adipocytes, chondrocytes and osteocytes confirmed their mesenchymal stromal cell status. Further, the HF-MSCs were positive for CD105, CD166, CD73, CD44, CD90, SSEA-4, and negative for CD34, CD45, HLA-DR cell-surface markers and were found to exhibit BM-MSC-like characteristics. hESC lines co-cultured with HF-MSC feeders showed expression of expected pluripotent transcription factors Oct-4, Nanog, Sox-2, GDF-3, Rex-1, STELLAR, ABCG2, Dppa5, hTERT; surface markers SSEA-4, TRA-1-81 and maintained their cytogenetic stability during long term passaging. These novel feeders also improved the formation of embryoid bodies (EBs) from hESC which produced cell types representing three germ layers. This culture system has the potential to aid the development of clinical-grade hESCs for regenerative medicine and drug screening. Further, we envisage foreskin can serve as a valuable source of alternative MSCs for specific therapeutic applications.
    Matched MeSH terms: Stromal Cells/metabolism
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