Displaying publications 1 - 20 of 35 in total

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  1. Gnanasegaran N, Govindasamy V, Musa S, Abu Kasim NH
    Cytotechnology, 2016 Mar;68(2):343-53.
    PMID: 25322895 DOI: 10.1007/s10616-014-9787-z
    Among the debilitating diseases, neurological related diseases are the most challenging ones to be treated using cell replacement therapies. Recently, dental pulp stem cells (SHED) were found to be most suitable cell choice for neurological related diseases as evidenced with many preclinical studies. To enhance the neurological potential of SHED, we recapitulated one of the pharmacological therapeutic tools in cell replacement treatment, we pre-conditioned dental pulp stem cells (SHED) with culture medium of ReNCell VM, an immortalized neuron progenitor cell, prior to neurogenesis induction and investigated whether this practice enhances their neurogenesis potential especially towards dopaminergic neurons. We hypothesed that the integration of pharmacological practices such as co-administration of various drugs, a wide range of doses and duration as well as pre-conditioning into cell replacement may enhance the efficacy of stem cell therapy. In particular, pre-conditioning is shown to be involved in the protective effect from some membrano-tropic drugs, thereby improving the resistance of cell structures and homing capabilities. We found that cells pre-treated with ReNCell VM conditioned medium displayed bipolar structures with extensive branches resembling putative dopaminergic neurons as compared to non-treated cells. Furthermore, many neuronal related markers such as NES, NR4A2, MSI1, and TH were highly expressed (fold changes > 2; p 
  2. Loo ZX, Kunasekaran W, Govindasamy V, Musa S, Abu Kasim NH
    ScientificWorldJournal, 2014;2014:186508.
    PMID: 25548778 DOI: 10.1155/2014/186508
    Human exfoliated deciduous teeth (SHED) and adipose stem cells (ASC) were suggested as alternative cell choice for cardiac regeneration. However, the true functionability of these cells toward cardiac regeneration is yet to be discovered. Hence, this study was carried out to investigate the innate biological properties of these cell sources toward cardiac regeneration. Both cells exhibited indistinguishable MSCs characteristics. Human stem cell transcription factor arrays were used to screen expression levels in SHED and ASC. Upregulated expression of transcription factor (TF) genes was detected in both sources. An almost equal percentage of >2-fold changes were observed. These TF genes fall under several cardiovascular categories with higher expressions which were observed in growth and development of blood vessel, angiogenesis, and vasculogenesis categories. Further induction into cardiomyocyte revealed ASC to express more significantly cardiomyocyte specific markers compared to SHED during the differentiation course evidenced by morphology and gene expression profile. Despite this, spontaneous cellular beating was not detected in both cell lines. Taken together, our data suggest that despite being defined as MSCs, both ASC and SHED behave differently when they were cultured in a same cardiomyocytes culture condition. Hence, vigorous characterization is needed before introducing any cell for treating targeted diseases.
  3. Vasanthan P, Govindasamy V, Gnanasegaran N, Kunasekaran W, Musa S, Abu Kasim NH
    J Cell Mol Med, 2015 Mar;19(3):566-80.
    PMID: 25475098 DOI: 10.1111/jcmm.12381
    MicroRNAs (miRNAs) are small non-coding RNAs that regulate translation of mRNA into protein and play a crucial role for almost all biological activities. However, the identification of miRNAs from mesenchymal stem cells (MSCs), especially from dental pulp, is poorly understood. In this study, dental pulp stem cells (DPSCs) were characterized in terms of their proliferation and differentiation capacity. Furthermore, 104 known mature miRNAs were profiled by using real-time PCR. Notably, we observed 19 up-regulated miRNAs and 29 significantly down-regulated miRNAs in DPSCs in comparison with bone marrow MSCs (BM-MSCs). The 19 up-regulated miRNAs were subjected to ingenuity analysis, which were composed into 25 functional networks. We have chosen top 2 functional networks, which comprised 10 miRNA (hsa-miR-516a-3p, hsa-miR-125b-1-3p, hsa-miR-221-5p, hsa-miR-7, hsa-miR-584-5p, hsa-miR-190a, hsa-miR-106a-5p, hsa-mir-376a-5p, hsa-mir-377-5p and hsa-let-7f-2-3p). Prediction of target mRNAs and associated biological pathways regulated by each of this miRNA was carried out. We paid special attention to hsa-miR-516a-3p and hsa-miR-7-5p as these miRNAs were highly expressed upon validation with qRT-PCR analysis. We further proceeded with loss-of-function analysis with these miRNAs and we observed that hsa-miR-516a-3p knockdown induced a significant increase in the expression of WNT5A. Likewise, the knockdown of hsa-miR-7-5p increased the expression of EGFR. Nevertheless, further validation revealed the role of WNT5A as an indirect target of hsa-miR-516a-3p. These results provide new insights into the dynamic role of miRNA expression in DPSCs. In conclusion, using miRNA signatures in human as a prediction tool will enable us to elucidate the biological processes occurring in DPSCs.
  4. Xin LZ, Govindasamy V, Musa S, Abu Kasim NH
    Med Hypotheses, 2013 Oct;81(4):704-6.
    PMID: 23932760 DOI: 10.1016/j.mehy.2013.07.032
    Dental tissues contains stem cells or progenitors that have high proliferative capacity, are clonogenic in vitro and demonstrate the ability to differentiate to multiple type cells involving neurons, bone, cartilage, fat and smooth muscle. Numerous experiments have demonstrated that the multipotent stem cells are not rejected by immune system and therefore it may be possible to use these cells in allogeneic settings. In addition, these remarkable cells are easily abundantly available couple with less invasive procedure in isolating comparing to bone marrow aspiration. Here we proposed dental stem cells as candidate for cardiac regeneration based on its immature characteristic and propensity towards cardiac lineage via PI3-Kinase/Aktsignalling pathway.
  5. Govindasamy V, Abdullah AN, Ronald VS, Musa S, Ab Aziz ZA, Zain RB, et al.
    J Endod, 2010 Sep;36(9):1504-15.
    PMID: 20728718 DOI: 10.1016/j.joen.2010.05.006
    Lately, several new stem cell sources and their effective isolation have been reported that claim to have potential for therapeutic applications. However, it is not yet clear which type of stem cell sources are most potent and best for targeted therapy. Lack of understanding of nature of these cells and their lineage-specific propensity might hinder their full potential. Therefore, understanding the gene expression profile that indicates their lineage-specific proclivity is fundamental to the development of successful cell-based therapies.
  6. Gnanasegaran N, Govindasamy V, Kathirvaloo P, Musa S, Abu Kasim NH
    J Tissue Eng Regen Med, 2018 02;12(2):e881-e893.
    PMID: 28079995 DOI: 10.1002/term.2401
    Parkinson's disease (PD) is characterized by tremors and cognitive issues, and is due to the death of dopaminergic (DA-ergic) neurons in brain circuits that are responsible for producing neurotransmitter dopamine (DA). Currently, cell replacement therapies are underway to improve upon existing therapeutic approaches such as drug treatments and electrical stimulation. Among the widely available sources, dental pulp stem cells (DPSCs) from deciduous teeth have gained popularity because of their neural crest origin and inherent propensity toward neuronal lineage. Despite the various pre-clinical studies conducted, an important factor yet to be elucidated is the influence of growth phases in a typical trans-differentiation process. This study selected DPSCs at three distinct time points with variable growth phase proportions (G0/G1, S and G2/M) for in vitro trans-differentiation into DA-ergic-like cells. Using commercially available PCR arrays, we identified distinct gene profiles pertaining to cell cycles in these phases. The differentiation outcomes were assessed in terms of morphology and gene and protein expression, as well as with functional assays. It was noted that DPSCs with the highest G0/G1 phase were comparatively the best, representing at least a 2-fold up regulation (p 
  7. Gnanasegaran N, Govindasamy V, Simon C, Gan QF, Vincent-Chong VK, Mani V, et al.
    Eur J Clin Invest, 2017 Mar 30.
    PMID: 28369799 DOI: 10.1111/eci.12753
    BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic (DA-ergic) neurons in the substantia nigra (SN) and represented as a huge threat to the geriatric population. Cell replacement therapies (CRTs) have been proposed as a promising strategy to slow down or replace neuronal loss. Among the widely available cell sources, dental pulp stem cells (DPSCs) portray as an attractive source primarily due to their neural crest origin, ease of tissue procurement and less ethical hurdles.

    MATERIALS AND METHODS: We first demonstrated the in vitro differentiation ability of DPSCs towards DA-ergic-like cells before evaluating their neuro-protection/neuro-restoration capacities in MPTP-induced mice. Transplantation via intrathecal was performed with behavioural assessments being evaluated every fortnight. Subsequent analysis investigating their immuno-modulatory behaviour was conducted using neuronal and microglial cell lines.

    RESULTS: It was apparent that the behavioural parameters began to improve corresponding to tyrosine hydroxylase (TH), dopamine transporter (DAT) and dopamine decarboxylase (AADC) immunostaining in SN and striatum as early as 8-week post-transplantation (P < 0·05). About 60% restoration of DA-ergic neurons was observed at SN in MPTP-treated mice after 12-week post-transplantation. Similarly, their ability to reduce toxic effects of MPTP (DNA damages, reactive oxygen species and nitric oxide release) and regulate cytokine levels was distinctly noted (P < 0·05) upon exposure in in vitro model.

    CONCLUSIONS: Our results suggest that DPSCs may provide a therapeutic benefit in the old-aged PD mice model and may be explored in stem cell-based CRTs especially in geriatric population as an attempt towards 'personalized medicine'.

  8. Manan NM, Musa S, Nor MMD, Saari CZ, Al-Namankany A
    Int J Paediatr Dent, 2024 May;34(3):267-276.
    PMID: 37985445 DOI: 10.1111/ipd.13132
    BACKGROUND: The Abeer Children Dental Anxiety Scale (ACDAS) source language was developed and validated in an English-speaking country in the UK to measure dental anxiety among children. The ACDAS also included the child's cognitive assessment, as well as feedback from the parent or the legal guardian and a dental health professional (DHP). This is the first study to validate the application of the ACDAS in Malay or Bahasa Melayu for children aged 6-16 years.

    AIM: To assess the Malay-translated version of the ACDAS, postadaptation into the local context and validation by the content and construct experts.

    DESIGN: The English ACDAS was translated into Malay first through forward translation and then through backward translation. The prefinal translated version of the instrument was designed, with the participation of 61 children and 61 parents or legal guardians. Subsequently, a final cross-cultural adaptation of the instrument was then made for another group of participants and evaluated for validity and test-retest reliability among 144 children and 144 parents or legal guardians participating in the self-report feedback process at the Paediatric Dental Clinic, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur, Malaysia. The cross-cultural adaptation of the instrument considered translating to Malaysian national language and adapting to its culture.

    RESULTS: The Malay-translated ACDAS consisted of 19 items. The translated version of Malaysian-ACDAS (MY-ACDAS) achieved an acceptable agreement between six expert committee members with an internal consistency (Cronbach's alpha value, αconsistency) of 0.839. The test-retest reliability results of all participants support semantic and conceptual equivalence as an accepted construct validity between the children, parents and DHPs across the multicultural Malaysian population.

    CONCLUSION: The MY-ACDAS is a valid and reliable scale for measuring dental anxiety among Malaysian children.

  9. Musa, S., Awang, H.
    Ann Dent, 1996;3(1):-.
    MyJurnal
    A case of mucosal burn during the placement of fissure sealant on the first permanent molars of a 9-year-old Malay boy is presented. The erythematous lesion with accompanying burning sensation appeared a few minutes after the etching liquid, containing 37% by weight phosphoric acid, had accidentally come into contact with the buccal mucosa on the right side of the angle of the mouth. The mucosa showed complete healing after one week. The use of rubber dam for tooth isolation while doing fissure sealant is essential to avoid accidental contact of potentially caustic chemicals, such as the phosphoric acid etchant, with the oral mucosa as it can result in mucosal burns.
  10. 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.
  11. 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.
  12. Govindasamy V, Ronald VS, Abdullah AN, Nathan KR, Ab Aziz ZA, Abdullah M, et al.
    J Dent Res, 2011 May;90(5):646-52.
    PMID: 21335539 DOI: 10.1177/0022034510396879
    The post-natal dental pulp tissue contains a population of multipotent mesenchymal progenitor cells known as dental pulp stromal/stem cells (DPSCs), with high proliferative potential for self-renewal. In this investigation, we explored the potential of DPSCs to differentiate into pancreatic cell lineage resembling islet-like cell aggregates (ICAs). We isolated, propagated, and characterized DPSCs and demonstrated that these could be differentiated into adipogenic, chondrogenic, and osteogenic lineage upon exposure to an appropriate cocktail of differentiating agents. Using a three-step protocol reported previously by our group, we succeeded in obtaining ICAs from DPSCs. The identity of ICAs was confirmed as islets by dithiozone-positive staining, as well as by expression of C-peptide, Pdx-1, Pax4, Pax6, Ngn3, and Isl-1. There were several-fold up-regulations of these transcription factors proportional to days of differentiation as compared with undifferentiated DPSCs. Day 10 ICAs released insulin and C-peptide in a glucose-dependent manner, exhibiting in vitro functionality. Our results demonstrated for the first time that DPSCs could be differentiated into pancreatic cell lineage and offer an unconventional and non-controversial source of human tissue that could be used for autologous stem cell therapy in diabetes.
  13. Srijaya TC, Pradeep PJ, Zain RB, Musa S, Abu Kasim NH, Govindasamy V
    Stem Cells Int, 2012;2012:423868.
    PMID: 22654919 DOI: 10.1155/2012/423868
    Induced pluripotent stem cell-based therapy for treating genetic disorders has become an interesting field of research in recent years. However, there is a paucity of information regarding the applicability of induced pluripotent stem cells in dental research. Recent advances in the use of induced pluripotent stem cells have the potential for developing disease-specific iPSC lines in vitro from patients. Indeed, this has provided a perfect cell source for disease modeling and a better understanding of genetic aberrations, pathogenicity, and drug screening. In this paper, we will summarize the recent progress of the disease-specific iPSC development for various human diseases and try to evaluate the possibility of application of iPS technology in dentistry, including its capacity for reprogramming some genetic orodental diseases. In addition to the easy availability and suitability of dental stem cells, the approach of generating patient-specific pluripotent stem cells will undoubtedly benefit patients suffering from orodental disorders.
  14. Jayaraman P, Nathan P, Vasanthan P, Musa S, Govindasamy V
    Cell Biol Int, 2013 Oct;37(10):1122-8.
    PMID: 23716460 DOI: 10.1002/cbin.10138
    Stem cell biology has gained remarkable interest in recent years, driven by the hope of finding cures for numerous diseases including skin wound healing through transplantation medicine. Initially upon transplantation, these cells home to and differentiate within the injured tissue into specialised cells. Contrariwise, it now appears that only a small percentage of transplanted cells integrate and survive in host tissues. Thus, the foremost mechanism by which stem cells participate in tissue repair seems to be related to their trophic factors. Indeed, stem cells provide the microenvironment with a wide range of growth factors, cytokines and chemokines, which can broadly defined as the stem cells secretome. In in vitro condition, these molecules can be traced from the conditioned medium or spent media harvested from cultured cells. Conditioned medium now serves as a new treatment modality in regenerative medicine and has shown a successful outcome in some diseases. With the emergence of this approach, we described the possibility of using stem cells conditioned medium as a novel and promising alternative to skin wound healing treatment. Numerous pre-clinical data have shown the possibility and efficacy of this treatment. Despite this, significant challenges need to be addressed before translating this technology to the bedside.
  15. Ahmad H, Thambiratnam K, Zulkifli AZ, Lawrence A, Jasim AA, Kunasekaran W, et al.
    Sensors (Basel), 2013 Sep 30;13(10):13276-88.
    PMID: 24084118 DOI: 10.3390/s131013276
    An efficient and low cost optical method for directly measuring the concentration of homogenous biological solutes is proposed and demonstrated. The proposed system operates by Fresnel reflection, with a flat-cleaved single-mode fiber serving as the sensor probe. A laser provides a 12.9 dBm sensor signal at 1,550 nm, while a computer-controlled optical power meter measures the power of the signal returned by the probe. Three different mesenchymal stem cell (MSC) lines were obtained, sub-cultured and trypsinized daily over 9 days. Counts were measured using a haemocytometer and the conditioned media (CM) was collected daily and stored at -80 °C. MSCs release excretory biomolecules proportional to their growth rate into the CM, which changes the refractive index of the latter. The sensor is capable of detecting changes in the number of stem cells via correlation to the change in the refractive index of the CM, with the measured power loss decreasing approximately 0.4 dB in the CM sample per average 1,000 cells in the MSC subculture. The proposed system is highly cost-effective, simple to deploy, operate, and maintain, is non-destructive, and allows reliable real-time measurement of various stem cell proliferation parameters.
  16. Rafieerad AR, Bushroa AR, Nasiri-Tabrizi B, Fallahpour A, Vadivelu J, Musa SN, et al.
    J Mech Behav Biomed Mater, 2016 08;61:182-196.
    PMID: 26874249 DOI: 10.1016/j.jmbbm.2016.01.028
    PVD process as a thin film coating method is highly applicable for both metallic and ceramic materials, which is faced with the necessity of choosing the correct parameters to achieve optimal results. In the present study, a GEP-based model for the first time was proposed as a safe and accurate method to predict the adhesion strength and hardness of the Nb PVD coated aimed at growing the mixed oxide nanotubular arrays on Ti67. Here, the training and testing analysis were executed for both adhesion strength and hardness. The optimum parameter combination for the scratch adhesion strength and micro hardness was determined by the maximum mean S/N ratio, which was 350W, 20 sccm, and a DC bias of 90V. Results showed that the values calculated in the training and testing in GEP model were very close to the actual experiments designed by Taguchi. The as-sputtered Nb coating with highest adhesion strength and microhardness was electrochemically anodized at 20V for 4h. From the FESEM images and EDS results of the annealed sample, a thick layer of bone-like apatite was formed on the sample surface after soaking in SBF for 10 days, which can be connected to the development of a highly ordered nanotube arrays. This novel approach provides an outline for the future design of nanostructured coatings for a wide range of applications.
  17. Gnanasegaran N, Govindasamy V, Musa S, Kasim NH
    Int J Med Sci, 2014;11(4):391-403.
    PMID: 24669199 DOI: 10.7150/ijms.7697
    Human adipose stem cells (ASCs) has been in the limelight since its discovery as a suitable source of mesenchymal stem cells (MSCs) in regenerative medicine. Currently, two major techniques are used to isolate ASCs, namely liposuction and tissue biopsy. These two methods are relatively risk-free but the question as to which method could give a more efficient output remains unclear. Thus, this study was carried out to compare and contrast the output generated in regards to growth kinetics, differentiation capabilities in vitro, and gene expression profiling. It was found that ASCs from both isolation methods were comparable in terms of growth kinetics and tri-lineage differentiation. Furthermore, ASCs from both populations were reported as CD44(+), CD73(+), CD90(+), CD166(+), CD34(-), CD45(-) and HLA-DR(-). However, in regards to gene expression, a group of overlapping genes as well as distinct genes were observed. Distinct gene expressions indicated that ASCs (liposuction) has endoderm lineage propensity whereas ASCs (biopsy) has a tendency towards mesoderm/ectoderm lineage. This information suggests involvement in different functional activity in accordance to isolation method. In conclusion, future studies to better understand these gene functions should be carried out in order to contribute in the applicability of each respective cells in regenerative therapy.
  18. Musa S, Xin LZ, Govindasamy V, Fuen FW, Kasim NH
    Expert Opin Biol Ther, 2014 Jan;14(1):63-73.
    PMID: 24191782 DOI: 10.1517/14712598.2014.858694
    Acute myocardial infarction is the primary cause of heart disease-related death in the world. Reperfusion therapy is currently the backbone of treatment for acute myocardial infarction albeit with many limitations. With the emergence of stem cells as potential therapeutic agents, attempts in using them to enhance cardiac function have increased exponentially. However, it has its own disadvantages, and we postulate that the primary drawback is choosing the right cell type and solving this may significantly contribute to ambitious goal of using stem cells in the regeneration medicine.
  19. Jayaraman P, Govindasamy V, Gnanasegaran N, Kunasekaran W, Vasanthan P, Musa S, et al.
    Clin Oral Investig, 2016 Jan;20(1):109-16.
    PMID: 26048030 DOI: 10.1007/s00784-015-1497-1
    Long-term culture system is used to prevent the impediment of insufficient cells and is good for low starting materials such as dental pulp or periodontal ligament. In general, although cell viability and functionality are the most common aspects taken into consideration in culturing cells for a long term, they may not truly represent the biological state of the cells. Hence, we explored the behaviour of another important aspect which is the immune properties in long-term cultured cells.
  20. Vasanthan P, Jayaraman P, Kunasekaran W, Lawrence A, Gnanasegaran N, Govindasamy V, et al.
    Naturwissenschaften, 2016 Aug;103(7-8):62.
    PMID: 27379400 DOI: 10.1007/s00114-016-1387-7
    Human deciduous periodontal ligament stem cells have been introduced for as an easily accessible source of stem cells from dental origin. Although recent studies have revealed the ability of these stem cells in multipotential attribute, their efficiency of hepatic lineage differentiation has not been addressed so far. The aim of this study is to investigate hepatic lineage fate competence of periodontal ligament stem cells through direct media induction. Differentiation of periodontal ligament stem cells into hepatocyte-like cells was conducted by the exposure of two phase media induction. First phase was performed in the presence of hepatocyte growth factors to induce a definitive endoderm formation. In the subsequent phase, the cells were treated with oncostatin M and dexamethosone followed by insulin and transferrin to generate hepatocyte-like cells. Hepatic-related characters of the generated hepatocyte-like cells were determined at both mRNA and protein level followed by functional assays. Foremost changes observed in the generation of hepatocyte-like cells were the morphological features in which these cells were transformed from fibroblastic shape to polygonal shape. Temporal expression of hepatic markers ranging from early endodermal up to late markers were detected in the hepatocyte-like cells. Crucial hepatic markers such as glycogen storage, albumin, and urea secretion were also shown. These findings exhibited the ability of periodontal ligament stem cells of dental origin to be directed into hepatic lineage fate. These cells can be regarded as an alternative autologous source in the usage of stem cell-based treatment for liver diseases.
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