Displaying publications 1 - 20 of 44 in total

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  1. Role of Sirtuin1-p53 regulatory axis in aging, cancer and cellular reprogramming
    Ong ALC, Ramasamy TS
    Ageing Res Rev, 2018 May;43:64-80.
    PMID: 29476819 DOI: 10.1016/j.arr.2018.02.004
    Regulatory role of Sirtuin 1 (SIRT1), one of the most extensively studied members of its kind in histone deacetylase family in governing multiple cellular fates, is predominantly linked to p53 activity. SIRT1 deacetylates p53 in a NAD+-dependent manner to inhibit transcription activity of p53, in turn modulate pathways that are implicated in regulation of tissue homoeostasis and many disease states. In this review, we discuss the role of SIRT1-p53 pathway and its regulatory axis in the cellular events which are implicated in cellular aging, cancer and reprogramming. It is noteworthy that these cellular events share few common regulatory pathways, including SIRT1-p53-LDHA-Myc, miR-34a,-Let7 regulatory network, which forms a positive feedback loop that controls cell cycle, metabolism, proliferation, differentiation, epigenetics and many others. In the context of aging, SIRT1 expression is reduced as a protective mechanism against oncogenesis and for maintenance of tissue homeostasis. Interestingly, its activation in aged cells is evidenced in response to DNA damage to protect the cells from p53-dependent apoptosis or senescence, predispose these cells to neoplastic transformation. Importantly, the dual roles of SIRT1-p53 axis in aging and tumourigenesis, either as tumour suppressor or tumour promoter are determined by SIRT1 localisation and type of cells. Conceptualising the distinct similarity between tumorigenesis and cellular reprogramming, this review provides a perspective discussion on involvement of SIRT1 in improving efficiency in the induction and maintenance of pluripotent state. Further research in understanding the role of SIRT1-p53 pathway and their associated regulators and strategies to manipulate this regulatory axis very likely foster the development of therapeutics and strategies for treating cancer and aging-associated degenerative diseases.
    Matched MeSH terms: Cell Differentiation/physiology
  2. Fulltext Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis
    Mellone M, Hanley CJ, Thirdborough S, Mellows T, Garcia E, Woo J, et al.
    Aging (Albany NY), 2016 12 15;9(1):114-132.
    PMID: 27992856 DOI: 10.18632/aging.101127
    Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo, showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head & neck (HNSCC) and esophageal (EAC) cancers. In vitro, we found that fibroblasts induced to senesce develop molecular, ultrastructural and contractile features typical of myofibroblasts and this is dependent on canonical TGF-β signaling. Similar to TGF-β1-generated myofibroblasts, these cells secrete soluble factors that promote tumor cell motility. However, RNA-sequencing revealed significant transcriptomic differences between the two SMA-positive CAF groups, particularly in genes associated with extracellular matrix (ECM) deposition and organization, which differentially promote tumor cell invasion. Notably, second harmonic generation imaging and bioinformatic analysis of SMA-positive human HNSCC and EAC showed that collagen fiber organization correlates with poor prognosis, indicating that heterogeneity within the SMA-positive CAF population differentially impacts on survival. These results show that non-fibrogenic, SMA-positive myofibroblasts can be directly generated through induction of fibroblast senescence and suggest that senescence and myofibroblast differentiation are closely linked processes.
    Matched MeSH terms: Cell Differentiation/physiology*
  3. Potential of human decidua stem cells for angiogenesis and neurogenesis
    Hayati AR, Nur Fariha MM, Tan GC, Tan AE, Chua K
    Arch Med Res, 2011 May;42(4):291-300.
    PMID: 21820607 DOI: 10.1016/j.arcmed.2011.06.005
    Placenta as a fetomaternal organ is a potential source of fetal as well as maternal stem cells. This present study describes novel properties of the cells isolated from the maternal part of term placenta membrane, the decidua basalis.
    Matched MeSH terms: Cell Differentiation/physiology
  4. Regulation of ITAM adaptor molecules and their receptors by inhibition of calcineurin-NFAT signalling during late stage osteoclast differentiation
    Zawawi MS, Dharmapatni AA, Cantley MD, McHugh KP, Haynes DR, Crotti TN
    Biochem Biophys Res Commun, 2012 Oct 19;427(2):404-9.
    PMID: 23000414 DOI: 10.1016/j.bbrc.2012.09.077
    Osteoclasts are specialised bone resorptive cells responsible for both physiological and pathological bone loss. Osteoclast differentiation and activity is dependent upon receptor activator NF-kappa-B ligand (RANKL) interacting with its receptor RANK to induce the transcription factor, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1). The immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway has been identified as a co-stimulatory pathway in osteoclasts. Osteoclast-associated receptor (OSCAR) and triggering receptor expressed in myeloid cells (TREM2) are essential receptors that pair with adaptor molecules Fc receptor common gamma chain (FcRγ) and DNAX-activating protein 12kDa (DAP12) respectively to induce calcium signalling. Treatment with calcineurin-NFAT inhibitors, Tacrolimus (FK506) and the 11R-VIVIT (VIVIT) peptide, reduces NFATc1 expression consistent with a reduction in osteoclast differentiation and activity. This study aimed to investigate the effects of inhibiting calcineurin-NFAT signalling on the expression of ITAM factors and late stage osteoclast genes including cathepsin K (CathK), Beta 3 integrin (β3) and Annexin VIII (AnnVIII). Human peripheral blood mononuclear cells (PBMCs) were differentiated with RANKL and macrophage-colony stimulating factor (M-CSF) over 10days in the presence or absence of FK506 or VIVIT. Osteoclast formation (as assessed by tartrate resistant acid phosphatase (TRAP)) and activity (assessed by dentine pit resorption) were significantly reduced with treatment. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that FK506 treatment significantly (p<0.05) reduced the expression of NFATc1, CathK, OSCAR, FcRγ, TREM2 and DAP12 during the terminal stage of osteoclast formation. VIVIT treatment significantly (p<0.05) decreased CathK, OSCAR, FcRγ, and AnnVIII, gene expression. This data suggest FK506 and VIVIT act differently in targeting the calcineurin-NFAT signalling cascade to suppress key mediators of the ITAM pathway during late stage osteoclast differentiation and this is associated with a reduction in both osteoclast differentiation and activity.
    Matched MeSH terms: Cell Differentiation/physiology*
  5. Long term mesenchymal stem cell culture on a defined synthetic substrate with enzyme free passaging
    Duffy CR, Zhang R, How SE, Lilienkampf A, De Sousa PA, Bradley M
    Biomaterials, 2014 Jul;35(23):5998-6005.
    PMID: 24780167 DOI: 10.1016/j.biomaterials.2014.04.013
    Mesenchymal stems cells (MSCs) are currently the focus of numerous therapeutic approaches in tissue engineering/repair because of their wide multi-lineage potential and their ability to modulate the immune system response following transplantation. Culturing these cells, while maintaining their multipotency in vitro, currently relies on biological substrates such as gelatin, collagen and fibronectin. In addition, harvesting cells from these substrates requires enzymatic or chemical treatment, a process that will remove a multitude of cellular surface proteins, clearly an undesirable process if cells are to be used therapeutically. Herein, we applied a high-throughput 'hydrogel microarray' screening approach to identify thermo-modulatable substrates which can support hES-MP and ADMSC growth, permit gentle reagent free passaging, whilst maintaining multi-lineage potential. In summary, the hydrogel substrate identified, poly(AEtMA-Cl-co-DEAA) cross-linked with MBA, permitted MSCs to be maintained over 10 passages (each time via thermo-modulation), with the cells retaining expression of MSC associated markers and lineage potency. This chemically defined system allowed the passaging and maintenance of cellular phenotype of this clinically important cell type, in the absence of harsh passaging and the need for biological substrates.
    Matched MeSH terms: Cell Differentiation/physiology
  6. Development of a bone substitute material based on alpha-tricalcium phosphate scaffold coated with carbonate apatite/poly-epsilon-caprolactone
    Bang LT, Ramesh S, Purbolaksono J, Long BD, Chandran H, Ramesh S, et al.
    Biomed Mater, 2015 Aug;10(4):045011.
    PMID: 26225725 DOI: 10.1088/1748-6041/10/4/045011
    Interconnected porous tricalcium phosphate ceramics are considered to be potential bone substitutes. However, insufficient mechanical properties when using tricalcium phosphate powders remain a challenge. To mitigate these issues, we have developed a new approach to produce an interconnected alpha-tricalcium phosphate (α-TCP) scaffold and to perform surface modification on the scaffold with a composite layer, which consists of hybrid carbonate apatite / poly-epsilon-caprolactone (CO3Ap/PCL) with enhanced mechanical properties and biological performance. Different CO3Ap combinations were tested to evaluate the optimal mechanical strength and in vitro cell response of the scaffold. The α-TCP scaffold coated with CO3Ap/PCL maintained a fully interconnected structure with a porosity of 80% to 86% and achieved an improved compressive strength mimicking that of cancellous bone. The addition of CO3Ap coupled with the fully interconnected microstructure of the α-TCP scaffolds coated with CO3Ap/PCL increased cell attachment, accelerated proliferation and resulted in greater alkaline phosphatase (ALP) activity. Hence, our bone substitute exhibited promising potential for applications in cancellous bone-type replacement.
    Matched MeSH terms: Cell Differentiation/physiology
  7. Fulltext Cell therapy: the final frontier for treatment of neurological diseases
    Dutta S, Singh G, Sreejith S, Mamidi MK, Husin JM, Datta I, et al.
    CNS Neurosci Ther, 2013 Jan;19(1):5-11.
    PMID: 23253099 DOI: 10.1111/cns.12027
    Neurodegenerative diseases are devastating because they cause increasing loss of cognitive and physical functions and affect an estimated 1 billion individuals worldwide. Unfortunately, no drugs are currently available to halt their progression, except a few that are largely inadequate. This mandates the search of new treatments for these progressively degenerative diseases. Neural stem cells (NSCs) have been successfully isolated, propagated, and characterized from the adult brains of mammals, including humans. The confirmation that neurogenesis occurs in the adult brain via NSCs opens up fresh avenues for treating neurological problems. The proof-of-concept studies demonstrating the neural differentiation capacity of stem cells both in vitro and in vivo have raised widespread enthusiasm toward cell-based interventions. It is anticipated that cell-based neurogenic drugs may reverse or compensate for deficits associated with neurological diseases. The increasing interest of the private sector in using human stem cells in therapeutics is evidenced by launching of several collaborative clinical research activities between Pharma giants and research institutions or small start-up companies. In this review, we discuss the major developments that have taken place in this field to position stem cells as a prospective candidate drug for the treatment of neurological disorders.
    Matched MeSH terms: Cell Differentiation/physiology
  8. A miRNA-145/TGF-β1 negative feedback loop regulates the cancer-associated fibroblast phenotype
    Melling GE, Flannery SE, Abidin SA, Clemmens H, Prajapati P, Hinsley EE, et al.
    Carcinogenesis, 2018 05 28;39(6):798-807.
    PMID: 29506142 DOI: 10.1093/carcin/bgy032
    The dissemination of cancer cells to local and distant sites depends on a complex and poorly understood interplay between malignant cells and the cellular and non-cellular components surrounding them, collectively termed the tumour microenvironment. One of the most abundant cell types of the tumour microenvironment is the fibroblast, which becomes corrupted by locally derived cues such as TGF-β1 and acquires an altered, heterogeneous phenotype (cancer-associated fibroblasts, CAF) supportive of tumour cell invasion and metastasis. Efforts to develop new treatments targeting the tumour mesenchyme are hampered by a poor understanding of the mechanisms underlying the development of CAF. Here, we examine the contribution of microRNA to the development of experimentally-derived CAF and correlate this with changes observed in CAF derived from tumours. Exposure of primary normal human fibroblasts to TGF-β1 resulted in the acquisition of a myofibroblastic CAF-like phenotype. This was associated with increased expression of miR-145, a miRNA predicted in silico to target multiple components of the TGF-β signalling pathway. miR-145 was also overexpressed in CAF derived from oral cancers. Overexpression of miR-145 blocked TGF-β1-induced myofibroblastic differentiation and reverted CAF towards a normal fibroblast phenotype. We conclude that miR-145 is a key regulator of the CAF phenotype, acting in a negative feedback loop to dampen acquisition of myofibroblastic traits, a key feature of CAF associated with poor disease outcome.
    Matched MeSH terms: Cell Differentiation/physiology
  9. Alteration of gene expression levels during osteogenic induction of human adipose derived stem cells in long-term culture
    Safwani WK, Makpol S, Sathapan S, Chua KH
    Cell Tissue Bank, 2013 Jun;14(2):289-301.
    PMID: 22476937 DOI: 10.1007/s10561-012-9309-1
    Adipose tissue is a source of multipotent stem cells and it has the ability to differentiate into several types of cell lineages such as neuron cells, osteogenic and adipogenic cells. Most studies on human adipose-derived stem cells (ASCs) have been carried out at the early passages. For clinical usage, ASCs need to be expanded in vitro for a period of time to get sufficient cells for transplantation into patients. However, the impact of long-term culture on ASCs molecular characteristics has not been established yet. Several studies have also shown that osteogenic and adipogenic cells have the ability to switch pathways during in vitro culture as they share the same progenitor cells. This data is important to ensure their functionality and efficacy before being used clinically in the treatment of bone diseases. Therefore, we aim to investigate the effect of long-term culture on the adipogenic, stemness and osteogenic genes expression during osteogenic induction of ASCs. In this study, the molecular characteristics of ASCs during osteogenic induction in long-term culture was analysed by observing their morphological changes during induction, analysis of cell mineralization using Alizarin Red staining and gene expression changes using quantitative RT-PCR. Morphologically, cell mineralization at P20 was less compared to P5, P10 and P15. Adipogenesis was not observed as negative lipid droplets formation was recorded during induction. The quantitative PCR data showed that adipogenic genes expression e.g. LPL and AP2 decreased but PPAR-γ was increased after osteogenic induction in long-term culture. Most stemness genes decreased at P5 and P10 but showed no significant changes at P15 and P20. While most osteogenic genes increased after osteogenic induction at all passages. When compared among passages after induction, Runx showed a significant increased at P20 while BSP, OSP and ALP decreased at later passage (P15 and P20). During long-term culture, ASCs were only able to differentiate into immature osteogenic cells.
    Matched MeSH terms: Cell Differentiation/physiology
  10. The microscopic biological response of human chondrocytes to bovine bone scaffold
    Abdullah B, Shibghatullah AH, Hamid SS, Omar NS, Samsuddin AR
    Cell Tissue Bank, 2009 Aug;10(3):205-13.
    PMID: 18975136 DOI: 10.1007/s10561-008-9111-2
    This study was performed to determine the microscopic biological response of human nasal septum chondrocytes and human knee articular chondrocytes placed on a demineralized bovine bone scaffold. Both chondrocytes were cultured and seeded onto the bovine bone scaffold with seeding density of 1 x 105 cells per 100 microl/scaffold and incubated for 1, 2, 5 and 7 days. Proliferation and viability of the cells were measured by mitochondrial dehydrogenase activity (MTT assay), adhesion study was analyzed by scanning electron microscopy and differentiation study was analyzed by immunofluorescence staining and confocal laser scanning electron microscopy. The results showed good proliferation and viability of both chondrocytes on the scaffolds from day 1 to day 7. Both chondrocytes increased in number with time and readily grew on the surface and into the open pores of the scaffold. Immunofluorescence staining demonstrated collagen type II on the scaffolds for both chondrocytes. The results showed good cells proliferation, attachment and maturity of the chondrocytes on the demineralized bovine bone scaffold. The bovine bone being easily resourced, relatively inexpensive and non toxic has good potential for use as a three dimensional construct in cartilage tissue engineering.
    Matched MeSH terms: Cell Differentiation/physiology
  11. Human mesenchymal stem cells promote CD34+hematopoietic stem cell proliferation with preserved red blood cell differentiation capacity
    Lau SX, Leong YY, Ng WH, Ng AWP, Ismail IS, Yusoff NM, et al.
    Cell Biol Int, 2017 Jun;41(6):697-704.
    PMID: 28403524 DOI: 10.1002/cbin.10774
    Studies showed that co-transplantation of mesenchymal stem cells (MSCs) and cord blood-derived CD34+hematopoietic stem cells (HSCs) offered greater therapeutic effects but little is known regarding the effects of human Wharton's jelly derived MSCs on HSC expansion and red blood cell (RBC) generation in vitro. This study aimed to investigate the effects of MSCs on HSC expansion and differentiation. HSCs were co-cultured with MSCs or with 10% MSCs-derived conditioned medium, with HSCs cultured under standard medium served as a control. Cell expansion rates, number of mononuclear cell post-expansion and number of enucleated cells post-differentiation were evaluated. HSCs showed superior proliferation in the presence of MSC with mean expansion rate of 3.5 × 108 ± 1.8 × 107after day 7 compared to the conditioned medium and the control group (8.9 × 107 ± 1.1 × 108and 7.0 × 107 ± 3.3 × 106respectively, P cell was greater compared to earlier passages, indicating successful RBC differentiation. Cord blood-derived CD34+HSCs can be greatly expanded by co-culturing with MSCs without affecting the RBC differentiation capability, suggesting the importance of direct MSC-HSCs contact in HSC expansion and RBC differentiation.
    Matched MeSH terms: Cell Differentiation/physiology
  12. Mesenchymal stem cells: From stem cells to sarcomas
    Lye KL, Nordin N, Vidyadaran S, Thilakavathy K
    Cell Biol Int, 2016 Jun;40(6):610-8.
    PMID: 26992453 DOI: 10.1002/cbin.10603
    Mesenchymal stem cells (MSCs) have garnered vast interests in clinical settings, especially in regenerative medicine due to their unique properties-they are reliably isolated and expanded from various tissue sources; they are able to differentiate into mesodermal tissues such as bones, cartilages, adipose tissues, and muscles; and they have unique immunosuppressive properties. However, there are some concerns pertaining to the role of MSCs in the human body. On one hand, they are crucial component in the regeneration and repair of the human body. On the contrary, they are shown to transform into sarcomas. Although the exact mechanisms are still unknown, many new leads have pointed to the belief that MSCs do play a role in sarcomagenesis. This review focuses on the current updates and findings of the role of MSCs in their transformation process into sarcomas.
    Matched MeSH terms: Cell Differentiation/physiology
  13. Hypoxia enhances the viability, growth and chondrogenic potential of cryopreserved human adipose-derived stem cells
    Wan Safwani WKZ, Choi JR, Yong KW, Ting I, Mat Adenan NA, Pingguan-Murphy B
    Cryobiology, 2017 04;75:91-99.
    PMID: 28108309 DOI: 10.1016/j.cryobiol.2017.01.006
    Cryopreservation is the only existing method of storage of human adipose-derived stem cells (ASCs) for clinical use. However, cryopreservation has been shown to be detrimental to ASCs, particularly in term of cell viability. To restore the viability of cryopreserved ASCs, it is proposed to culture the cells in a hypoxic condition. To this end, we aim to investigate the effect of hypoxia on the cryopreserved human ASCs in terms of not only cell viability, but also their growth and stemness properties, which have not been explored yet. In this study, human ASCs were cultured under four different conditions: fresh (non-cryopreserved) cells cultured in 1) normoxia (21% O2) and 2) hypoxia (2% O2) and cryopreserved cells cultured in 3) normoxia and 4) hypoxia. ASCs at passage 3 were subjected to assessment of viability, proliferation, differentiation, and expression of stemness markers and hypoxia-inducible factor-1 alpha (HIF-1α). We found that hypoxia enhances the viability and the proliferation rate of cryopreserved ASCs. Further, hypoxia upregulates HIF-1α in cryopreserved ASCs, which in turn activates chondrogenic genes to promote chondrogenic differentiation. In conclusion, hypoxic-preconditioned cryopreserved ASCs could be an ideal cell source for cartilage repair and regeneration.
    Matched MeSH terms: Cell Differentiation/physiology
  14. Stem Cells Derived from Amniotic Fluid: A Potential Pluripotent-Like Cell Source for Cellular Therapy?
    Ramasamy TS, Velaithan V, Yeow Y, Sarkar FH
    Curr Stem Cell Res Ther, 2018;13(4):252-264.
    PMID: 29336267 DOI: 10.2174/1574888X13666180115093800
    BACKGROUND: Regenerative medicine aims to provide therapeutic treatment for disease or injury, and cell-based therapy is a newer therapeutic approach different from conventional medicine. Ethical issues that rose by the utilisation of human embryonic stem cells (hESC) and the limited capacity of adult stem cells, however, hinder the application of these stem cells in regenerative medicine. Recently, isolation and characterisation of c-kit positive cells from human amniotic fluid, which possess intermediate characteristics between hESCs and adult stem cells, provided a new approach towards realising their promise for fetal and adult regenerative medicine. Despite the number of studies that have been initiated to characterize their molecular signature, research on developing approaches to maintain and enhance their regenerative potential is urgently needed and must be developed.

    AIM: Thus, this review is focused on understanding their potential uses and factors influencing their pluripotent status in vitro.

    CONCLUSION: In short, this cell source could be an ideal cellular resource for pluripotent cells for potential applications in allogeneic cellular replacement therapies, fetal tissue engineering, pharmaceutical screening, and in disease modelling.

    Matched MeSH terms: Cell Differentiation/physiology*
  15. Retropatellar fat pad-derived stem cells from older osteoarthritic patients have lesser differentiation capacity and expression of stemness genes
    Chua KH, Zaman Wan Safwani WK, Hamid AA, Shuhup SK, Mohd Haflah NH, Mohd Yahaya NH
    Cytotherapy, 2014 May;16(5):599-611.
    PMID: 24290076 DOI: 10.1016/j.jcyt.2013.08.013
    The use of retropatellar fat pad-derived mesenchymal stromal cells (RFMSCs) for cell-based therapy, particularly for cartilage repair, has been reported by several investigators in recent years. However, the effects of the donor's age and medical condition on the characteristics of RFMSCs have not been well established. The aim of this study was to determine whether age and medical condition can reduce the multipotential of stem cells isolated from the retropatellar fat pad.
    Matched MeSH terms: Cell Differentiation/physiology*
  16. Engineering physical microenvironment for stem cell based regenerative medicine
    Han YL, Wang S, Zhang X, Li Y, Huang G, Qi H, et al.
    Drug Discov Today, 2014 Jun;19(6):763-73.
    PMID: 24508818 DOI: 10.1016/j.drudis.2014.01.015
    Regenerative medicine has rapidly evolved over the past decade owing to its potential applications to improve human health. Targeted differentiations of stem cells promise to regenerate a variety of tissues and/or organs despite significant challenges. Recent studies have demonstrated the vital role of the physical microenvironment in regulating stem cell fate and improving differentiation efficiency. In this review, we summarize the main physical cues that are crucial for controlling stem cell differentiation. Recent advances in the technologies for the construction of physical microenvironment and their implications in controlling stem cell fate are also highlighted.
    Matched MeSH terms: Cell Differentiation/physiology
  17. Fulltext Impaired redox environment modulates cardiogenic and ion-channel gene expression in cardiac-resident and non-resident mesenchymal stem cells
    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: Cell Differentiation/physiology
  18. Differentiation of stem cells derived from carious teeth into dopaminergic-like cells
    Gnanasegaran N, Govindasamy V, Abu Kasim NH
    Int Endod J, 2016 Oct;49(10):937-49.
    PMID: 26354006 DOI: 10.1111/iej.12545
    AIM: To investigate whether dental pulp stem cells from carious teeth (DPSCs-CT) can differentiate into functional dopaminergic-like (DAergic) cells and provide an alternative cell source in regenerative medicine.

    METHODOLOGY: Dental pulp stem cells from healthy (DPSCs) and carious teeth (DPSCs-CT) were isolated from young donors. Both cell lines were expanded in identical culture conditions and subsequently differentiated towards DAergic-like cells using pre-defined dopaminergic cocktails. The dopaminergic efficiencies were evaluated both at gene and protein as well as at secretome levels.

    RESULTS: The efficiency of DPSCs-CT to differentiate into DAergic-like cells was not equivalent to that of DPSCs. This was further reflected in both gene and protein generation whereby key neuronal markers such as nestin, NURR1 and beta-III-tubulin were expressed significantly lower as compared to differentiated DPSCs (P cell communication family (APBB1).

    CONCLUSIONS: DPSCs-CT were able to differentiate into DAergic-like cells but not as efficiently as DPSCs. As such, prior to use in regenerative medicine, stem cells from any source should be thoroughly investigated beyond conventional benchmarks such as that proposed by the International Society for Cellular Therapy (ISCT).

    Matched MeSH terms: Cell Differentiation/physiology*
  19. Fulltext Heterogeneity of osteosarcoma cell lines led to variable responses in reprogramming
    Choong PF, Teh HX, Teoh HK, Ong HK, Choo KB, Sugii S, et al.
    Int J Med Sci, 2014;11(11):1154-60.
    PMID: 25170299 DOI: 10.7150/ijms.8281
    Four osteosarcoma cell lines, Saos-2, MG-63, G-292 and U-2 OS, were reprogrammed to pluripotent state using Yamanaka factors retroviral transduction method. Embryonic stem cell (ESC)-like clusters started to appear between 15 to 20 days post transduction. Morphology of the colonies resembled that of ESC colonies with defined border and tightly-packed cells. The reprogrammed sarcomas expressed alkaline phosphatase and pluripotency markers, OCT4, SSEA4, TRA-1-60 and TRA-1-81, as in ESC up to Passage 15. All reprogrammed sarcomas could form embryoid body-like spheres when cultured in suspension in a low attachment dish for up to 10 days. Further testing on the directed differentiation capacity of the reprogrammed sarcomas showed all four reprogrammed sarcoma lines could differentiate into adipocytes while reprogrammed Saos-2-REP, MG-63-REP and G-292-REP could differentiate into osteocytes. Among the 4 osteosarcoma cell lines, U-2 OS reported the highest transduction efficiency but recorded the lowest reprogramming stability under long term culture. Thus, there may be intrinsic differences governing the variable responses of osteosarcoma cell lines towards reprogramming and long term culture effect of the reprogrammed cells. This is a first report to associate intrinsic factors in different osteosarcoma cell lines with variable reprogramming responses and effects on the reprogrammed cells after prolonged culture.
    Matched MeSH terms: Cell Differentiation/physiology
  20. Fulltext Three-dimensional culture environment increases the efficacy of platelet rich plasma releasate in prompting skin fibroblast differentiation and extracellular matrix formation
    Rothan HA, Djordjevic I, Bahrani H, Paydar M, Ibrahim F, Abd Rahmanh N, et al.
    Int J Med Sci, 2014;11(10):1029-38.
    PMID: 25136258 DOI: 10.7150/ijms.8895
    Platelet rich plasma clot- releasate (PRCR) shows significant influence on tissue regeneration in clinical trials. Although, the mechanism of PRCR effect on fibroblast differentiation has been studied on 2D culture system, a detailed investigation is needed to establish the role of PRCR in cell seeded in 3D scaffolds. Therefore, a study was conducted to evaluate the influence of PRCR in fibroblasts (DFB) differentiation and extracellular matrix formation on both 3D and 2D culture systems. Cell viability was measured using MTT assay and DFB differentiation was evaluated by determining the expression levels of nucleostamin and alpha smooth muscle actin (α-SMA), using indirect immunostaining and Western blotting. The expression levels of extracellular matrix genes (collagen-I, collagen-III, fibronectin and laminin) and focal adhesion formation gene (integrin beta-1) were measured using Real-time PCR. The PRCR at 10% showed significant effect on cells viability compared with 5% and 20% in both culture environments. The decrease in the expression levels of nucleostamin and the increase in α-SMA signify the DFB differentiation to myofibroblast-like cells that was prominently greater in 3D compared to 2D culture. In 3D culture systems, the total collage production, expression levels of the extracellular matrix gene and the focal adhesion gene were increased significantly compared to 2D culture. In conclusion, 3D culture environments enhances the proliferative and differentiation effects of PRCR on DFB, thereby potentially increases the efficacy of DFB for future tissue engineering clinical application.
    Matched MeSH terms: Cell Differentiation/physiology*
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