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Recently, dental tissues have been identified as a potential source of mesenchymal stem cells (MSCs) and several populations of MSCs were isolated from the orofacial region, including gingival mesenchymal stem cells (GMSCs). GMSCs exhibit robust immunomodulatory and differentiation potential and are easily obtainable, which make them promising candidates for cellular therapies. Apart from being tested for application in immunologic- and inflammatory-related disorders and various tissue regeneration, GMSCs promise to be a valuable tool in cancer treatment, especially in tongue squamous cell carcinoma (TSCC) with the use of targeted therapy, since GMSCs are able to selectively migrate towards the cancerous cells both in vitro and in vivo. In addition to their ability to uptake and release anti-neoplastic drugs, GMSCs may be transduced with apoptosis-inducing factors and used for cancer growth inhibition. Moreover, GMSCs, as most mammalian cells, secrete exosomes, which are a subset of extracellular vesicles with a diameter of 40\u2013160 nm, containing DNA, RNA, lipids, metabolites, and proteins. Such GMSCs-derived exosomes may be useful therapeutic tool in cell-free therapy, as well as their culture medium. GMSCs exhibit molecular and stem-cell properties that make them well suited in preclinical and clinical studies.<\/jats:p>","DOI":"10.3390\/cells9081916","type":"journal-article","created":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T11:15:27Z","timestamp":1597749327000},"page":"1916","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Stemness Potency of Human Gingival Cells\u2014Application in Anticancer Therapies and Clinical Trials"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8814-4935","authenticated-orcid":false,"given":"Katarzyna","family":"Stefa\u0144ska","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Poznan University of Medical Sciences, 6 \u015awi\u0119cickiego St., 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Mehr","sequence":"additional","affiliation":[{"name":"Department of Gerostomatology and Pathology of Oral Cavity, Poznan University of Medical Sciences, 70 Bukowska St., 60-812 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4960-2817","authenticated-orcid":false,"given":"Maria","family":"Wieczorkiewicz","sequence":"additional","affiliation":[{"name":"Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 7 Gagarina St., 87-100 Torun, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1098-5627","authenticated-orcid":false,"given":"Magdalena","family":"Kulus","sequence":"additional","affiliation":[{"name":"Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 7 Gagarina St., 87-100 Torun, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5661-0807","authenticated-orcid":false,"given":"Ana","family":"Angelova Volponi","sequence":"additional","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology, Dental Institute, King\u2019s College London, Strand, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1971-0195","authenticated-orcid":false,"given":"Jamil A.","family":"Shibli","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Oral Implantology, Dental Research Division, Guarulhos University, Guarulhos, R. 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(2008). Mesenchymal stem cells in health and disease. Nat. Rev. Immunol.","DOI":"10.1038\/nri2395"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/j.1365-2184.1970.tb00347.x","article-title":"The Development of Fibroblast Colonies in Monolayer Cultures of Guinea-Pig Bone Marrow and Spleen Cells","volume":"3","author":"Friedenstein","year":"1970","journal-title":"Cell Prolif."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pittenger, M.F., Mackay, A.M., Beck, S.C., Jaiswal, R.K., Douglas, R., Mosca, J.D., Moorman, M.A., Simonetti, D.W., Craig, S., and Marshak, D.R. (1999). Multilineage potential of adult human mesenchymal stem cells. Science.","DOI":"10.1126\/science.284.5411.143"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1089\/ten.tea.2009.0709","article-title":"Human adipose-derived mesenchymal stem cells: Direction to a phenotype sharing similarities with the disc, gene expression profiling, and coculture with human annulus cells","volume":"16","author":"Gruber","year":"2010","journal-title":"Tissue Eng. Part A"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"In\u2019t Anker, P.S., Scherjon, S.A., Kleijburg-van der Keur, C., de Groot-Swings, G.M.J.S., Claas, F.H.J., Fibbe, W.E., and Kanhai, H.H.H. (2004). Isolation of Mesenchymal Stem Cells of Fetal or Maternal Origin from Human Placenta. Stem Cells.","DOI":"10.1634\/stemcells.2004-0058"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"In \u2019t Anker, P.S., Scherjon, S.A., Kleijburg-van der Keur, C., Noort, W.A., Claas, F.H.J., Willemze, R., Fibbe, W.E., and Kanhai, H.H.H. (2003). Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood.","DOI":"10.1182\/blood-2003-04-1291"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Campagnoli, C., Roberts, I.A.G., Kumar, S., Bennett, P.R., Bellantuono, I., and Fisk, N.M. (2001). Identification of mesenchymal stem\/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood.","DOI":"10.1182\/blood.V98.8.2396"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1634\/stemcells.2007-0381","article-title":"Multipotent Stem Cells from Umbilical Cord: Cord Is Richer than Blood!","volume":"26","author":"Secco","year":"2008","journal-title":"Stem Cells"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1007\/s00018-015-1833-2","article-title":"Molecular basis of embryonic stem cell self-renewal: From signaling pathways to pluripotency network","volume":"72","author":"Huang","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gronthos, S., Mankani, M., Brahim, J., Robey, P.G., and Shi, S. (2000). Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc. Natl. Acad. Sci. USA.","DOI":"10.1073\/pnas.240309797"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Miura, M., Gronthos, S., Zhao, M., Lu, B., Fisher, L.W., Robey, P.G., and Shi, S. (2003). SHED: Stem cells from human exfoliated deciduous teeth. Proc. Natl. Acad. Sci. USA.","DOI":"10.1073\/pnas.0937635100"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Seo, B.M., Miura, M., Gronthos, S., Bartold, P.M., Batouli, S., Brahim, J., Young, M., Robey, P.G., Wang, C.Y., and Shi, S. (2004). Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet.","DOI":"10.1016\/S0140-6736(04)16627-0"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.matbio.2004.12.004","article-title":"Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth","volume":"24","author":"Morsczeck","year":"2005","journal-title":"Matrix Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1359\/JBMR.041117","article-title":"Alveolar bone marrow as a cell source for regenerative medicine: Differences between alveolar and iliac bone marrow stromal cells","volume":"20","author":"Matsubara","year":"2005","journal-title":"J. Bone Miner. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sonoyama, W., Liu, Y., Fang, D., Yamaza, T., Seo, B.M., Zhang, C., Liu, H., Gronthos, S., Wang, C.Y., and Shi, S. (2006). Mesenchymal stem cell-mediated functional tooth regeneration in Swine. PLoS ONE.","DOI":"10.1371\/journal.pone.0000079"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ikeda, E., Yagi, K., Kojima, M., Yagyuu, T., Ohshima, A., Sobajima, S., Tadokoro, M., Katsube, Y., Isoda, K., and Kondoh, M. (2008). Multipotent cells from the human third molar: Feasibility of cell-based therapy for liver disease. Differentiation.","DOI":"10.1111\/j.1432-0436.2007.00245.x"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7787","DOI":"10.4049\/jimmunol.0902318","article-title":"Mesenchymal Stem Cells Derived from Human Gingiva Are Capable of Immunomodulatory Functions and Ameliorate Inflammation-Related Tissue Destruction in Experimental Colitis","volume":"183","author":"Zhang","year":"2009","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Xu, X., Chen, C., Akiyama, K., Chai, Y., Le, A.D., Wang, Z., and Shi, S. (2013). Gingivae contain neural-crest- and mesoderm-derived mesenchymal stem cells. J. Dent. Res.","DOI":"10.1177\/0022034513497961"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Fawzy El-Sayed, K.M., and D\u00f6rfer, C.E. (2016). Gingival Mesenchymal Stem\/Progenitor Cells: A Unique Tissue Engineering Gem. Stem Cells Int.","DOI":"10.1155\/2016\/7154327"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Eslami, A., Gallant-Behm, C.L., Hart, D.A., Wiebe, C., Honardoust, D., Gardner, H., H\u00e4kkinen, L., and Larjava, H.S. (2009). Expression of integrin \u03b1v\u03b26 and TGF-\u03b2 in Scarless vs Scar-forming wound healing. J. Histochem. Cytochem.","DOI":"10.1369\/jhc.2009.952572"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lodi, D., Iannitti, T., and Palmieri, B. (2011). Stem cells in clinical practice: Applications and warnings. J. Exp. Clin. Cancer Res.","DOI":"10.1186\/1756-9966-30-9"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mitrano, T.I., Grob, M.S., Carri\u00f3n, F., Nova-Lamperti, E., Luz, P.A., Fierro, F.S., Quintero, A., Chaparro, A., and Sanz, A. (2010). Culture and Characterization of Mesenchymal Stem Cells From Human Gingival Tissue. J. Periodontol.","DOI":"10.1902\/jop.2010.090566"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"El-Sayed, K.M.F., Paris, S., Graetz, C., Kassem, N., Mekhemar, M., Ungefroren, H., F\u00e4ndrich, F., and D\u00f6rfer, C. (2015). Isolation and characterisation of human gingival margin-derived STRO-1\/MACS (+) and MACS (\u2212) cell populations. Int. J. Oral Sci.","DOI":"10.1038\/ijos.2014.41"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"El-Bialy, T., Alhadlaq, A., Wong, B., and Kucharski, C. (2014). Ultrasound effect on neural differentiation of gingival stem\/progenitor cells. Ann. Biomed. Eng.","DOI":"10.1007\/s10439-014-1013-9"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Fournier, B.P.J., Ferre, F.C., Couty, L., Lataillade, J.J., Gourven, M., Naveau, A., Coulomb, B., Lafont, A., and Gogly, B. (2010). Multipotent progenitor cells in gingival connective tissue. Tissue Eng. Part A.","DOI":"10.1089\/ten.tea.2009.0796"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ranga Rao, S., and Subbarayan, R. (2019). Passage-dependent expression of STRO-1 in human gingival mesenchymal stem cells. J. Cell. Biochem.","DOI":"10.1002\/jcb.27674"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"20982","DOI":"10.3390\/ijms151120982","article-title":"Isolation and multiple differentiation potential assessment of human gingival mesenchymal stem cells","volume":"15","author":"Gao","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tang, L., Li, N., Xie, H., and Jin, Y. (2011). Characterization of mesenchymal stem cells from human normal and hyperplastic gingiva. J. Cell. Physiol.","DOI":"10.1002\/jcp.22405"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Tomar, G.B., Srivastava, R.K., Gupta, N., Barhanpurkar, A.P., Pote, S.T., Jhaveri, H.M., Mishra, G.C., and Wani, M.R. (2010). Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine. Biochem. Biophys. Res. Commun.","DOI":"10.1016\/j.bbrc.2010.01.126"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ge, S., Mrozik, K.M., Menicanin, D., Gronthos, S., and Bartold, P.M. (2012). Isolation and characterization of mesenchymal stem cell-like cells from healthy and inflamed gingival tissue: Potential use for clinical therapy. Regen. Med.","DOI":"10.2217\/rme.12.61"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1111\/jre.12228","article-title":"Isolation and characterization of human mesenchymal stem cells from gingival connective tissue","volume":"50","author":"Jin","year":"2015","journal-title":"J. Periodontal Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1177\/0022034512461016","article-title":"Human oral mucosa and gingiva: A unique reservoir for mesenchymal stem Cells","volume":"91","author":"Zhang","year":"2012","journal-title":"J. Dent. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Nguyen, A.L., Shi, S., Hill, C., Wilder-Smith, P., Krasieva, T.B., and Le, A.D. (2012). Three-dimensional spheroid culture of human gingiva-derived mesenchymal stem cells enhances mitigation of chemotherapy-induced oral mucositis. Stem Cells Dev.","DOI":"10.1089\/scd.2011.0252"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wu, S.M., Chiu, H.C., Chin, Y.T., Lin, H.Y., Chiang, C.Y., Tu, H.P., Fu, M.M.J., and Fu, E. (2014). Effects of enamel matrix derivative on the proliferation and osteogenic differentiation of human gingival mesenchymal stem cells. Stem Cell Res. Ther.","DOI":"10.1186\/scrt441"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Sun, Q., Nakata, H., Yamamoto, M., Kasugai, S., and Kuroda, S. (2019). Comparison of gingiva-derived and bone marrow mesenchymal stem cells for osteogenesis. J. Cell. Mol. Med.","DOI":"10.1111\/jcmm.14632"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lee, S.I., Ko, Y., and Park, J.B. (2017). Evaluation of the osteogenic differentiation of gingiva-derived stem cells grown on culture plates or in stem cell spheroids: Comparison of two- and three-dimensional cultures. Exp. Ther. Med.","DOI":"10.3892\/etm.2017.4813"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yuan, W.X., Wang, X.X., Zheng, D.H., Ma, D., Cui, Q., Yang, F., and Zhang, J. (2019). Muscone promotes the adipogenic differentiation of human gingival mesenchymal stem cells by inhibiting the wnt\/\u03b2-catenin signaling pathway. Drug Des. Devel. Ther.","DOI":"10.2147\/DDDT.S220970"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Marynka-Kalmani, K., Treves, S., Yafee, M., Rachima, H., Gafni, Y., Cohen, M.A., and Pitaru, S. (2010). The lamina propria of adult human oral mucosa harbors a novel stem cell population. Stem Cells.","DOI":"10.1002\/stem.425"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gugliandolo, A., Diomede, F., Scionti, D., Bramanti, P., Trubiani, O., and Mazzon, E. (2019). The Role of Hypoxia on the Neuronal Differentiation of Gingival Mesenchymal Stem Cells: A Transcriptional Study. Cell Transplant.","DOI":"10.1177\/0963689718814470"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Soundara Rajan, T., Giacoppo, S., Scionti, D., Diomede, F., Grassi, G., Pollastro, F., Piattelli, A., Bramanti, P., Mazzon, E., and Trubiani, O. (2017). Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J. Cell. Biochem.","DOI":"10.1002\/jcb.25815"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Rao, S.R., Subbarayan, R., Dinesh, M.G., Arumugam, G., and Raja, S.T.K. (2016). Differentiation of human gingival mesenchymal stem cells into neuronal lineages in 3D bioconjugated injectable protein hydrogel construct for the management of neuronal disorder. Exp. Mol. Med.","DOI":"10.1038\/emm.2015.113"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1007\/s10439-016-1594-6","article-title":"Muscle Tissue Engineering Using Gingival Mesenchymal Stem Cells Encapsulated in Alginate Hydrogels Containing Multiple Growth Factors","volume":"44","author":"Ansari","year":"2016","journal-title":"Ann. Biomed. Eng."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zhou, L.L., Liu, W., Wu, Y.M., Sun, W.L., D\u00f6rfer, C.E., and Fawzy El-Sayed, K.M. (2020). Oral Mesenchymal Stem\/Progenitor Cells: The Immunomodulatory Masters. Stem Cells Int.","DOI":"10.1155\/2020\/1327405"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Li, W., Ren, G., Huang, Y., Su, J., Han, Y., Li, J., Chen, X., Cao, K., Chen, Q., and Shou, P. (2012). Mesenchymal stem cells: A double-edged sword in regulating immune responses. Cell Death Differ.","DOI":"10.1038\/cdd.2012.26"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Davies, L.C., L\u00f6nnies, H., Locke, M., Sundberg, B., Rosendahl, K., G\u00f6therstr\u00f6m, C., Le Blanc, K., and Stephens, P. (2012). Oral mucosal progenitor cells are potently immunosuppressive in a dose-independent manner. Stem Cells Dev.","DOI":"10.1089\/scd.2011.0434"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Jiang, C.M., Liu, J., Zhao, J.Y., Xiao, L., An, S., Gou, Y.C., Quan, H.X., Cheng, Q., Zhang, Y.L., and He, W. (2015). Effects of hypoxia on the immunomodulatory properties of human gingiva-derived mesenchymal stem cells. J. Dent. Res.","DOI":"10.1177\/0022034514557671"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Akiyama, K., Chen, C., Wang, D., Xu, X., Qu, C., Yamaza, T., Cai, T., Chen, W., Sun, L., and Shi, S. (2012). Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-\/FAS-mediated T cell apoptosis. Cell Stem Cell.","DOI":"10.1016\/j.stem.2012.03.007"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Su, W.R., Zhang, Q.Z., Shi, S.H., Nguyen, A.L., and Le, A.D. (2011). Human gingiva-derived mesenchymal stromal cells attenuate contact hypersensitivity via prostaglandin E 2-dependent mechanisms. Stem Cells.","DOI":"10.1002\/stem.738"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Sayed, B.A., Christy, A., Quirion, M.R., and Brown, M.A. (2008). The Master Switch: The Role of Mast Cells in Autoimmunity and Tolerance. Annu. Rev. Immunol.","DOI":"10.1146\/annurev.immunol.26.021607.090320"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhang, Q.Z., Su, W.R., Shi, S.H., Wilder-Smith, P., Xiang, A.P., Wong, A., Nguyen, A.L., Kwon, C.W., and Le, A.D. (2010). Human gingiva-derived mesenchymal stem cells elicit polarization of M2 macrophages and enhance cutaneous wound healing. Stem Cells.","DOI":"10.1002\/stem.503"},{"key":"ref_52","first-page":"7627","article-title":"Human gingiva tissue-derived MSC ameliorates immune-mediated bone marrow failure of aplastic anemia via suppression of Th1 and Th17 cells and enhancement of CD4 + Foxp3 + regulatory T cells differentiation","volume":"11","author":"Zhao","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1002\/stem.187","article-title":"Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging","volume":"27","author":"Kidd","year":"2009","journal-title":"Stem Cells"},{"key":"ref_54","first-page":"2891","article-title":"Mesenchymal stem cells inhibited development of lung cancer induced by chemical carcinogens in a rat model","volume":"9","author":"Liu","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Albarenque, S.M., Zwacka, R.M., and Mohr, A. (2011). Both human and mouse mesenchymal stem cells promote breast cancer metastasis. Stem Cell Res.","DOI":"10.1016\/j.scr.2011.05.002"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1038\/onc.2009.130","article-title":"Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells","volume":"28","author":"Walter","year":"2009","journal-title":"Oncogene"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Zhang, T., Lee, W.Y.W., Rui, Y.F., Cheng, T.Y., Jiang, X.H., and Li, G. (2013). Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors. Stem Cell Res. Ther., 4.","DOI":"10.1186\/scrt221"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"17460","DOI":"10.1073\/pnas.1206653109","article-title":"Critical role for lysyl oxidase in mesenchymal stem cell-driven breast cancer malignancy","volume":"109","author":"Bell","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5885","DOI":"10.4049\/jimmunol.0903143","article-title":"Mesenchymal Stem Cells Protect Breast Cancer Cells through Regulatory T Cells: Role of Mesenchymal Stem Cell-Derived TGF-\u03b2","volume":"184","author":"Patel","year":"2010","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/sctm.18-0117","article-title":"Mesenchymal Stem Cell Administration Attenuates Colon Cancer Progression by Modulating the Immune Component within the Colorectal Tumor Microenvironment","volume":"8","author":"Usunier","year":"2019","journal-title":"Stem Cells Transl. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.canlet.2014.06.018","article-title":"Adipose tissue-derived mesenchymal stem cells cultured at high density express IFN-\u03b2 and suppress the growth of MCF-7 human breast cancer cells","volume":"352","author":"Ryu","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.3892\/ijo.2016.3715","article-title":"Mesenchymal stem cells derived from normal gingival tissue inhibit the proliferation of oral cancer cells in vitro and in vivo","volume":"49","author":"Ji","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Xia, L., Peng, R., Leng, W., Jia, R., Zeng, X., Yang, X., and Fan, M. (2015). TRAIL-expressing gingival-derived mesenchymal stem cells inhibit tumorigenesis of tongue squamous cell carcinoma. J. Dent. Res.","DOI":"10.1177\/0022034514557815"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Sgaramella, N., Gu, X., Boldrup, L., Coates, P.J., Fahraeus, R., Califano, L., Tartaro, G., Colella, G., Spaak, L.N., and Strom, A. (2018). Searching For New Targets And Treatments In The Battle Against Squamous Cell Carcinoma Of The Head And Neck, With Specific Focus On Tumours Of The Tongue. Curr. Top. Med. Chem., 18.","DOI":"10.2174\/1568026618666180116121624"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.1111\/cas.13775","article-title":"Novel therapeutic strategies for advanced ovarian cancer by using induced pluripotent stem cell-derived myelomonocytic cells producing interferon beta","volume":"109","author":"Imamura","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1038\/bjc.2013.422","article-title":"Interferon-\u03b2 gene-modified human bone marrow mesenchymal stem cells attenuate hepatocellular carcinoma through inhibiting AKT\/FOXO3a pathway","volume":"109","author":"Xie","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.lungcan.2010.01.003","article-title":"Human umbilical cord matrix-derived stem cells expressing interferon-\u03b2 gene significantly attenuate bronchioloalveolar carcinoma xenografts in SCID mice","volume":"70","author":"Matsuzuka","year":"2010","journal-title":"Lung Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Du, L., Liang, Q., Ge, S., Yang, C., and Yang, P. (2019). The growth inhibitory effect of human gingiva-derived mesenchymal stromal cells expressing interferon-\u03b2 on tongue squamous cell carcinoma cells and xenograft model. Stem Cell Res. Ther.","DOI":"10.1186\/s13287-019-1320-z"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Cocc\u00e8, V., Farronato, D., Brini, A.T., Masia, C., Giann\u00ec, A.B., Piovani, G., Sisto, F., Alessandri, G., Angiero, F., and Pessina, A. (2017). Drug Loaded Gingival Mesenchymal Stromal Cells (GinPa-MSCs) Inhibit In Vitro Proliferation of Oral Squamous Cell Carcinoma. Sci. Rep.","DOI":"10.1038\/s41598-017-09175-4"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Moshaverinia, A., Xu, X., Chen, C., Ansari, S., Zadeh, H.H., Snead, M.L., and Shi, S. (2014). Application of stem cells derived from the periodontal ligament orgingival tissue sources for tendon tissue regeneration. Biomaterials.","DOI":"10.1016\/j.biomaterials.2013.12.053"},{"key":"ref_71","first-page":"611","article-title":"Bone regeneration potential of stem cells derived from periodontal ligament or gingival tissue sources encapsulated in RGD-modified alginate scaffold","volume":"20","author":"Moshaverinia","year":"2014","journal-title":"Tissue Eng. Part A"},{"key":"ref_72","first-page":"4922","article-title":"Systemically transplanted human gingiva-derived mesenchymal stem cells contributing to bone tissue regeneration","volume":"7","author":"Xu","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Wang, F., Yu, M., Yan, X., Wen, Y., Zeng, Q., Yue, W., Yang, P., and Pei, X. (2011). Gingiva-derived mesenchymal stem cell-mediated therapeutic approach for bone tissue regeneration. Stem Cells Dev.","DOI":"10.1089\/scd.2010.0523"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Diomede, F., Gugliandolo, A., Scionti, D., Merciaro, I., Cavalcanti, M.F., Mazzon, E., and Trubiani, O. (2018). Biotherapeutic effect of gingival stem cells conditioned medium in bone tissue restoration. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020329"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Shi, A., Heinayati, A., Bao, D., Liu, H., Ding, X., Tong, X., Wang, L., Wang, B., and Qin, H. (2019). Small molecule inhibitor of TGF-\u03b2 signaling enables robust osteogenesis of autologous GMSCs to successfully repair minipig severe maxillofacial bone defects. Stem Cell Res. Ther.","DOI":"10.1186\/s13287-019-1281-2"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Sun, W., Wang, Z., Xu, Q., Sun, H., Liu, X., Yang, J., and Hong, R. (2019). The treatment of systematically transplanted gingival mesenchymal stem cells in periodontitis in mice. Exp. Ther. Med.","DOI":"10.3892\/etm.2019.7165"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Liu, X., Wang, Z., Song, W., Sun, W., Hong, R., Pothukuchi, A., and Xu, Q. (2019). Systematically transplanted human gingiva-derived mesenchymal stem cells regulate lipid metabolism and inflammation in hyperlipidemic mice with periodontitis. Exp. Ther. Med.","DOI":"10.3892\/etm.2019.8256"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Qiu, J., Wang, X., Zhou, H., Zhang, C., Wang, Y., Huang, J., Liu, M., Yang, P., and Song, A. (2020). Enhancement of periodontal tissue regeneration by conditioned media from gingiva-derived or periodontal ligament-derived mesenchymal stem cells: A comparative study in rats. Stem Cell Res. Ther.","DOI":"10.1186\/s13287-019-1546-9"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Nguyen, P.D., Shi, S., Burrell, J.C., Cullen, D.K., and Le, A.D. (2018). 3D bio-printed scaffold-free nerve constructs with human gingiva-derived mesenchymal stem cells promote rat facial nerve regeneration. Sci. Rep.","DOI":"10.1038\/s41598-018-24888-w"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Mammana, S., Gugliandolo, A., Cavalli, E., Diomede, F., Iori, R., Zappacosta, R., Bramanti, P., Conti, P., Fontana, A., and Pizzicannella, J. (2019). Human gingival mesenchymal stem cells pretreated with vesicular moringin nanostructures as a new therapeutic approach in a mouse model of spinal cord injury. J. Tissue Eng. Regen. Med.","DOI":"10.1002\/term.2857"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Rajan, T.S., Diomede, F., Bramanti, P., Trubiani, O., and Mazzon, E. (2017). Conditioned medium from human gingival mesenchymal stem cells protects motor-neuron-like NSC-34 cells against scratch-injury-induced cell death. Int. J. Immunopathol. Pharmacol.","DOI":"10.1177\/0394632017740976"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Li, P., Zhao, Y., and Ge, L. (2016). Therapeutic effects of human gingiva-derived mesenchymal stromal cells on murine contact hypersensitivity via prostaglandin E2-EP3 signaling. Stem Cell Res. Ther.","DOI":"10.1186\/s13287-016-0361-9"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Chen, M., Su, W., Lin, X., Guo, Z., Wang, J., Zhang, Q., Brand, D., Ryffel, B., Huang, J., and Liu, Z. (2013). Adoptive transfer of human gingiva-derived mesenchymal stem cells ameliorates collagen-induced arthritis via suppression of Th1 and Th17 cells and enhancement of regulatory T cell differentiation. Arthritis Rheum.","DOI":"10.1002\/art.37894"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Gu, Y., and Shi, S. (2016). Transplantation of gingiva-derived mesenchymal stem cells ameliorates collagen-induced arthritis. Arthritis Res. Ther.","DOI":"10.1186\/s13075-016-1160-5"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Luo, Y., Wu, W., Gu, J., Zhang, X., Dang, J., Wang, J., Zheng, Y., Huang, F., Yuan, J., and Xue, Y. (2019). Human gingival tissue-derived MSC suppress osteoclastogenesis and bone erosion via CD39-adenosine signal pathway in autoimmune arthritis. EBioMedicine.","DOI":"10.1016\/j.ebiom.2019.04.058"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Huang, F., Chen, M., Chen, W., Gu, J., Yuan, J., Xue, Y., Dang, J., Su, W., Wang, J., and Zadeh, H.H. (2017). Human gingiva-derived mesenchymal stem cells inhibit xeno-graft-versus-host disease via CD39-CD73-adenosine and IDO signals. Front. Immunol.","DOI":"10.3389\/fimmu.2017.00068"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Ni, X., Xia, Y., Zhou, S., Peng, H., Wu, X., Lu, H., Wang, H., Liu, R., Blazar, B.R., and Gu, J. (2019). Reduction in murine acute GVHD severity by human gingival tissue-derived mesenchymal stem cells via the CD39 pathways. Cell Death Dis.","DOI":"10.1038\/s41419-018-1273-7"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Zhang, W., Zhou, L., Dang, J., Zhang, X., Wang, J., Chen, Y., Liang, J., Li, D., Ma, J., and Yuan, J. (2017). Human Gingiva-Derived Mesenchymal Stem Cells Ameliorate Streptozoticin-induced T1DM in mice via Suppression of T effector cells and Up-regulating Treg Subsets. Sci. Rep.","DOI":"10.1038\/s41598-017-14979-5"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Kalluri, R., and LeBleu, V.S. (2020). The biology, function, and biomedical applications of exosomes. Science.","DOI":"10.1126\/science.aau6977"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Lane, R.E., Korbie, D., Anderson, W., Vaidyanathan, R., and Trau, M. (2015). Analysis of exosome purification methods using a model liposome system and tunable-resistive pulse sensing. Sci. Rep.","DOI":"10.1038\/srep07639"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Tschuschke, M., Kocherova, I., Bryja, A., Mozdziak, P., Angelova Volponi, A., Janowicz, K., Sibiak, R., Piotrowska-Kempisty, H., I\u017cycki, D., and Bukowska, D. (2020). Inclusion Biogenesis, Methods of Isolation and Clinical Application of Human Cellular Exosomes. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020436"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Rao, F., Zhang, D., Fang, T., Lu, C., Wang, B., Ding, X., Wei, S., Zhang, Y., Pi, W., and Xu, H. (2019). Exosomes from human gingiva-derived mesenchymal stem cells combined with biodegradable chitin conduits promote rat sciatic nerve regeneration. Stem Cells Int.","DOI":"10.1155\/2019\/2546367"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Shi, Q., Qian, Z., Liu, D., Sun, J., Wang, X., Liu, H., Xu, J., and Guo, X. (2017). GMSC-derived exosomes combined with a chitosan\/silk hydrogel sponge accelerates wound healing in a diabetic rat skin defect model. Front. Physiol.","DOI":"10.3389\/fphys.2017.00904"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Shi, S., Xu, Q., Zhang, Q., Shanti, R.M., and Le, A.D. (2019). SIS-ECM Laden with GMSC-Derived Exosomes Promote Taste Bud Regeneration. J. Dent. 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