Gingiva-derived Mesenchymal Stem Cells and Their Potential Applications in Oral and Maxillofacial Diseases

Xudong       Gao; Zhengguo       Cao
doi:10.2174/1574888X14666191107100311
Abstract

Background: Stem cells are undifferentiated cells with multilineage differentiation potential. They can be collected from bone marrow, fat, amniotic fluid, and teeth. Stem cell-based therapies have been widely used to treat multiple diseases, such as cardiac disease, and hematological disorders. The cells may also be beneficial for controlling the disease course and promoting tissue regeneration in oral and maxillofacial diseases. Oral-derived gingival mesenchymal stem cells are easy to access and the donor sites heal rapidly without a scar. Such characteristics demonstrate the beneficial role of GMSCs in oral and maxillofacial diseases.
Objective: We summarize the features of GMSCs, including their self-renewal, multipotent differentiation, immunomodulation, and anti-inflammation properties. We also discuss their applications in oral and maxillofacial disease treatment and tissue regeneration.
Conclusion: GMSCs are easily harvestable adult stem cells with outstanding proliferation, differentiation, and immunomodulation characteristics. A growing body of evidence indicates that GMSCs have strong potential use in accelerating wound healing and promoting the regeneration of bone defects, periodontium, oral neoplasms, salivary glands, peri-implantitis, and nerves. Moreover, alginate, polylactic acid and polycaprolactone can be used as biodegradable scaffolds for GMSC encapsulation. Various growth factors can be applied to the corresponding scaffolds to obtain the desired GMSC differentiation and phenotypes. Three-dimensional spheroid culture systems could optimize GMSC properties and improve the performance of the cells in tissue engineering. The immunomodulatory property of GMSCs in controlling oral and maxillofacial inflammation needs further research.
Keywords: GMSCs, multipotent, oral, regeneration, scaffold, tissue engineering.
« Previous Next »
[1] 
Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell  2004; 116(5): 639-48.
[http://dx.doi.org/10.1016/S0092-8674(04)00208-9] [PMID:  15006347] 
[2] 
Hernández-Monjaraz B, Santiago-Osorio E, Monroy-García A, Ledesma-Martínez E, Mendoza-Núñez VM. Mesenchymal stem cells of dental origin for inducing tissue regeneration in periodontitis: A mini-review. Int J Mol Sci  2018; 19(4)E944
[http://dx.doi.org/10.3390/ijms19040944] [PMID:  29565801] 
[3] 
Tassi SA, Sergio NZ, Misawa MYO, Villar CC. Efficacy of stem cells on periodontal regeneration: Systematic review of pre-clinical studies. J Periodontal Res  2017; 52(5): 793-812.
[http://dx.doi.org/10.1111/jre.12455] [PMID:  28394043] 
[4] 
Cui D, Li H, Xu X, et al. Mesenchymal stem cells for cartilage regeneration of TMJ osteoarthritis. Stem Cells Int 2017.20175979741
[http://dx.doi.org/10.1155/2017/5979741] [PMID:  29123550] 
[5] 
Yang B, Qiu Y, Zhou N, et al. Application of stem cells in oral disease therapy: Progresses and perspectives. Front Physiol  2017; 8: 197.
[http://dx.doi.org/10.3389/fphys.2017.00197] [PMID:  28421002] 
[6] 
  Sylvester KG, Longaker MT. Stem cells: Review and update Archives of surgery (Chicago, Ill: 1960) 2004; 2004(139): 93-.  
[http://dx.doi.org/10.1001/archsurg.139.1.93] 
[7] 
Dresser R. Stem cell research as innovation: Expanding the ethical and policy conversation. J Law Med Ethics  2010; 38(2): 332-41.
[8] 
Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell: entity or function? Cell  2001; 105(7): 829-41.
[http://dx.doi.org/10.1016/S0092-8674(01)00409-3] [PMID:  11439179] 
[9] 
Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science  1997; 276(5309): 71-4.
[http://dx.doi.org/10.1126/science.276.5309.71] [PMID:  9082988] 
[10] 
De Gemmis P, Lapucci C, Bertelli M, et al. A real-time PCR approach to evaluate adipogenic potential of amniotic fluid-derived human mesenchymal stem cells. Stem Cells Dev  2006; 15(5): 719-28.
[http://dx.doi.org/10.1089/scd.2006.15.719] [PMID:  17105407] 
[11] 
Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA  2000; 97(25): 13625-30.
[http://dx.doi.org/10.1073/pnas.240309797] [PMID:  11087820] 
[12] 
De Ugarte DA, Morizono K, Elbarbary A, et al. Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs (Print)  2003; 174(3): 101-9.
[http://dx.doi.org/10.1159/000071150] [PMID:  12835573] 
[13] 
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell  2006; 126(4): 663-76.
[http://dx.doi.org/10.1016/j.cell.2006.07.024] [PMID:  16904174] 
[14] 
   Caplan AI. Mesenchymal stem cells Journal of orthopaedic research: Official publication of the Orthopaedic Research Society 1991; 9(5): 641-50. [http://dx.doi.org/10.1002/jor.1100090504]  
[15] 
Atashi F, Modarressi A, Pepper MS. The role of reactive oxygen species in mesenchymal stem cell adipogenic and osteogenic differentiation: a review. Stem Cells Dev  2015; 24(10): 1150-63.
[http://dx.doi.org/10.1089/scd.2014.0484] [PMID:  25603196] 
[16] 
Kargozar S, Mozafari M, Hamzehlou S, et al. Bone tissue engineering using human cells: A comprehensive review on recent trends, current prospects, and recommendations. Appl Sci (Basel)  2019; 9: 174.
[http://dx.doi.org/10.3390/app9010174] 
[17] 
Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells - current trends and future prospective. Biosci Rep  2015; 35(2)e00191
[http://dx.doi.org/10.1042/BSR20150025] [PMID:  25797907] 
[18] 
Richardson SM, Kalamegam G, Pushparaj PN, et al. Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration. Methods  2016; 99: 69-80.
[http://dx.doi.org/10.1016/j.ymeth.2015.09.015] [PMID:  26384579] 
[19] 
Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy  2006; 8(4): 315-7.
[http://dx.doi.org/10.1080/14653240600855905] [PMID:  16923606] 
[20] 
Sharpe PT. Dental mesenchymal stem cells. Development  2016; 143(13): 2273-80.
[http://dx.doi.org/10.1242/dev.134189] [PMID:  27381225] 
[21] 
Xin LZ, Govindasamy V, Musa S, Abu Kasim NH. Dental stem cells as an alternative source for cardiac regeneration. Med Hypotheses  2013; 81(4): 704-6.
[http://dx.doi.org/10.1016/j.mehy.2013.07.032] [PMID:  23932760] 
[22] 
Miura M, Gronthos S, Zhao M, et al. SHED: Stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci USA  2003; 100(10): 5807-12.
[http://dx.doi.org/10.1073/pnas.0937635100] [PMID:  12716973] 
[23] 
Seo BM, Miura M, Gronthos S, et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet  2004; 364(9429): 149-55.
[http://dx.doi.org/10.1016/S0140-6736(04)16627-0] [PMID:  15246727] 
[24] 
Sonoyama W, Liu Y, Fang D, et al. Mesenchymal stem cellmediated functional tooth regeneration in swine. PLoS One 2006; 1e79  
[http://dx.doi.org/10.1371/journal.pone.0000079] [PMID: 17183711] 
[25] 
Morsczeck C, Gotz W, Schierholz J, et al. Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol  2005; 24(2): 155-65.
[26] 
Mitrano TI, Grob MS, Carrión F, et al. Culture and characterization of mesenchymal stem cells from human gingival tissue. J Periodontol  2010; 81(6): 917-25.
[http://dx.doi.org/10.1902/jop.2010.090566] [PMID:  20450355] 
[27] 
Zhang Q, Shi S, Liu Y, et al. Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis. J Immunol (Baltimore, Md: 1950) 2009; 183(12): 7787-98. 
[http://dx.doi.org/10.4049/jimmunol.0902318] 
[28] 
Fournier BP, Ferre FC, Couty L, et al. Multipotent progenitor cells in gingival connective tissue. Tissue Eng Part A  2010; 16(9): 2891-9.
[http://dx.doi.org/10.1089/ten.tea.2009.0796] [PMID:  20412029] 
[29] 
Jin SH, Lee JE, Yun JH, Kim I, Ko Y, Park JB. Isolation and characterization of human mesenchymal stem cells from gingival connective tissue. J Periodontal Res  2015; 50(4): 461-7.
[http://dx.doi.org/10.1111/jre.12228] [PMID:  25229614] 
[30] 
Tang L, Li N, Xie H, Jin Y. Characterization of mesenchymal stem cells from human normal and hyperplastic gingiva. J Cell Physiol  2011; 226(3): 832-42.
[http://dx.doi.org/10.1002/jcp.22405] [PMID:  20857425] 
[31] 
Ge S, Mrozik KM, Menicanin D, Gronthos S, Bartold PM. Isolation and characterization of mesenchymal stem cell-like cells from healthy and inflamed gingival tissue: potential use for clinical therapy. Regen Med  2012; 7(6): 819-32.
[http://dx.doi.org/10.2217/rme.12.61] [PMID:  23164082] 
[32] 
Tomasello L, Mauceri R, Coppola A, et al. Mesenchymal stem cells derived from inflamed dental pulpal and gingival tissue: a potential application for bone formation. Stem Cell Res Ther  2017; 8(1): 179.
[http://dx.doi.org/10.1186/s13287-017-0633-z] [PMID:  28764802] 
[33] 
Tomar GB, Srivastava RK, Gupta N, et al. 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  2010; 393(3): 377-83.
[http://dx.doi.org/10.1016/j.bbrc.2010.01.126] [PMID:  20138833] 
[34] 
Ferré FC, Larjava H, Loison-Robert LS, et al. Formation of cartilage and synovial tissue by human gingival stem cells. Stem Cells Dev  2014; 23(23): 2895-907.
[http://dx.doi.org/10.1089/scd.2013.0547] [PMID:  25003637] 
[35] 
Uccelli A, Pistoia V, Moretta L. Mesenchymal stem cells: A new strategy for immunosuppression? Trends Immunol  2007; 28(5): 219-26.
[http://dx.doi.org/10.1016/j.it.2007.03.001] [PMID:  17400510] 
[36] 
Caplan AI. Mesenchymal stem cells: Time to change the name! Stem Cells Transl Med  2017; 6(6): 1445-51.
[http://dx.doi.org/10.1002/sctm.17-0051] [PMID:  28452204] 
[37] 
  Gao F, Chiu SM, Motan DA, et al. Mesenchymal stem cells and immunomodulation: Current status and future prospects. Cell Death Dis 2016; 7e2062  
[http://dx.doi.org/10.1038/cddis.2015.327] [PMID: 26794657] 
[38] 
Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L. Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: Role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood  2008; 111(3): 1327-33.
[http://dx.doi.org/10.1182/blood-2007-02-074997] [PMID:  17951526] 
[39] 
Li Z, Jiang CM, An S, et al. Immunomodulatory properties of dental tissue-derived mesenchymal stem cells. Oral Dis  2014; 20(1): 25-34.
[http://dx.doi.org/10.1111/odi.12086] [PMID:  23463961] 
[40] 
Sotiropoulou PA, Perez SA, Gritzapis AD, Baxevanis CN, Papamichail M. Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells  2006; 24(1): 74-85.
[http://dx.doi.org/10.1634/stemcells.2004-0359] [PMID:  16099998] 
[41] 
Ren G, Su J, Zhang L, et al. Species variation in the mechanisms of mesenchymal stem cell-mediated immunosuppression. Stem Cells  2009; 27(8): 1954-62.
[http://dx.doi.org/10.1002/stem.118] [PMID:  19544427] 
[42] 
Sato K, Ozaki K, Oh I, et al. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood  2007; 109(1): 228-34.
[http://dx.doi.org/10.1182/blood-2006-02-002246] [PMID:  16985180] 
[43] 
Selmani Z, Naji A, Zidi I, et al. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells. Stem Cells  2008; 26(1): 212-22.
[http://dx.doi.org/10.1634/stemcells.2007-0554] [PMID:  17932417] 
[44] 
Xu X, Chen C, Akiyama K, et al. Gingivae contain neural-crest- and mesoderm-derived mesenchymal stem cells. J Dent Res  2013; 92(9): 825-32.
[http://dx.doi.org/10.1177/0022034513497961] [PMID:  23867762] 
[45] 
Zhang X, Huang F, Li W, et al. Human gingiva-derived mesenchymal stem cells modulate monocytes/macrophages and alleviate atherosclerosis. Front Immunol  2018; 9: 878.
[http://dx.doi.org/10.3389/fimmu.2018.00878] [PMID:  29760701] 
[46] 
Hong R, Wang Z, Sui A, et al. Gingival mesenchymal stem cells attenuate pro-inflammatory macrophages stimulated with oxidized low-density lipoprotein and modulate lipid metabolism. Arch Oral Biol  2019; 98: 92-8.
[http://dx.doi.org/10.1016/j.archoralbio.2018.11.007] [PMID:  30468993] 
[47] 
Zhang QZ, Su WR, Shi SH, et al. Human gingiva-derived mesenchymal stem cells elicit polarization of m2 macrophages and enhance cutaneous wound healing. Stem Cells  2010; 28(10): 1856-68.
[http://dx.doi.org/10.1002/stem.503] [PMID:  20734355] 
[48] 
Su WR, Zhang QZ, Shi SH, Nguyen AL, Le AD. Human gingiva-derived mesenchymal stromal cells attenuate contact hypersensitivity via prostaglandin E2-dependent mechanisms. Stem Cells  2011; 29(11): 1849-60.
[http://dx.doi.org/10.1002/stem.738] [PMID:  21987520] 
[49] 
Aboushady IM, Salem ZA, Sabry D, Mohamed A. Comparative study of the osteogenic potential of mesenchymal stem cells derived from different sources. J Clin Exp Dent  2018; 10(1): e7-e13.
[PMID:  29670709] 
[50] 
Subbarayan R, Murugan Girija D, Mukherjee J, Mamidanna SRR, Ranga Rao S. Comparision of Gingival and Umbilical Cord Stem Cells Based on Its Modulus and Neuronal Differentiation. J Cell Biochem  2017; 118(8): 2000-8.
[http://dx.doi.org/10.1002/jcb.25918] [PMID:  28145578] 
[51] 
Santamaría S, Sanchez N, Sanz M, Garcia-Sanz JA. Comparison of periodontal ligament and gingiva-derived mesenchymal stem cells for regenerative therapies. Clin Oral Investig  2017; 21(4): 1095-102.
[http://dx.doi.org/10.1007/s00784-016-1867-3] [PMID:  27270903] 
[52] 
Gao Y, Zhao G, Li D, Chen X, Pang J, Ke J. Isolation and multiple differentiation potential assessment of human gingival mesenchymal stem cells. Int J Mol Sci  2014; 15(11): 20982-96.
[http://dx.doi.org/10.3390/ijms151120982] [PMID:  25405732] 
[53] 
Xing Y, Zhang Y, Wu X, Zhao B, Ji Y, Xu X. A comprehensive study on donor-matched comparisons of three types of mesenchymal stem cells-containing cells from human dental tissue. J Periodontal Res  2019; 54(3): 286-99.
[http://dx.doi.org/10.1111/jre.12630] [PMID:  30474138] 
[54] 
Otabe K, Muneta T, Kawashima N, Suda H, Tsuji K, Sekiya I. Comparison of gingiva, dental pulp, and periodontal ligament cells from the standpoint of mesenchymal stem cell properties. Cell Med  2012; 4(1): 13-21.
[http://dx.doi.org/10.3727/215517912X653319] [PMID:  26858852] 
[55] 
Yang H, Gao LN, An Y, et al. Comparison of mesenchymal stem cells derived from gingival tissue and periodontal ligament in different incubation conditions. Biomaterials  2013; 34(29): 7033-47.
[http://dx.doi.org/10.1016/j.biomaterials.2013.05.025] [PMID:  23768902] 
[56] 
Angelopoulos I, Brizuela C, Khoury M. Gingival mesenchymal stem cells outperform haploidentical dental pulp-derived mesenchymal stem cells in proliferation rate, migration ability, and angiogenic potential. Cell Transplant  2018; 27(6): 967-78.
[http://dx.doi.org/10.1177/0963689718759649] [PMID:  29770705] 
[57] 
Grawish ME. Gingival-derived mesenchymal stem cells: An endless resource for regenerative dentistry. World J Stem Cells  2018; 10(9): 116-8.
[http://dx.doi.org/10.4252/wjsc.v10.i9.116] [PMID:  30310530] 
[58] 
Vincent A, Kohlert S, Lee TS, Inman J, Ducic Y. Free-flap reconstruction of the tongue. Semin Plast Surg  2019; 33(1): 38-45.
[http://dx.doi.org/10.1055/s-0039-1677789] [PMID:  30863211] 
[59] 
 Zhang Y, Shi S, Xu Q, et al. SIS-ECM Laden with GMSC-Derived Exosomes Promote Taste Bud Regeneration. J Dent Res 2018.22034518804531 
[PMID: 30335555] 
[60] 
Xu Q, Shanti RM, Zhang Q, Cannady SB, O’Malley BW Jr, Le AD. A Gingiva-derived mesenchymal stem cell-laden porcine small intestinal submucosa extracellular matrix construct promotes myomucosal regeneration of the tongue. Tissue Eng Part A  2017; 23(7-8): 301-12.
[http://dx.doi.org/10.1089/ten.tea.2016.0342] [PMID:  27923325] 
[61] 
Zhang Q, Nguyen AL, Shi S, et al. Three-dimensional spheroid culture of human gingiva-derived mesenchymal stem cells enhances mitigation of chemotherapy-induced oral mucositis. Stem Cells Dev  2012; 21(6): 937-47.
[http://dx.doi.org/10.1089/scd.2011.0252] [PMID:  21689066] 
[62] 
Abd El-Latif N, Abdulrahman M, Helal M, Grawish ME. Regenerative capacity of allogenic gingival margin- derived stem cells with fibrin glue on albino rats’ partially dissected submandibular salivary glands. Arch Oral Biol  2017; 82: 302-9.
[http://dx.doi.org/10.1016/j.archoralbio.2017.06.030] [PMID:  28688332] 
[63] 
Ansari S, Diniz IM, Chen C, et al. Human periodontal ligament- and gingiva-derived mesenchymal stem cells promote nerve regeneration when encapsulated in alginate/hyaluronic acid 3D scaffold. Adv Healthc Mater  2017; 6(24)
[http://dx.doi.org/10.1002/adhm.201700670] [PMID:  29076281] 
[64] 
Gugliandolo A, Diomede F, Cardelli P, et al. Transcriptomic analysis of gingival mesenchymal stem cells cultured on 3D bioprinted scaffold: A promising strategy for neuroregeneration. J Biomed Mater Res A  2018; 106(1): 126-37.
[http://dx.doi.org/10.1002/jbm.a.36213] [PMID:  28879677] 
[65] 
Zhang Q, Nguyen PD, Shi S, et al. Neural crest stem-like cells non-genetically induced from human gingiva-derived mesenchymal stem cells promote facial nerve regeneration in rats. Mol Neurobiol  2018; 55(8): 6965-83.
[http://dx.doi.org/10.1007/s12035-018-0913-3] [PMID:  29372546] 
[66] 
Zhang Q, Nguyen PD, Shi S, Burrell JC, Cullen DK, Le AD. 3D bio-printed scaffold-free nerve constructs with human gingiva-derived mesenchymal stem cells promote rat facial nerve regeneration. Sci Rep  2018; 8(1): 6634.
[http://dx.doi.org/10.1038/s41598-018-24888-w] [PMID:  29700345] 
[67] 
Mao Q, Nguyen PD, Shanti RM, et al. Gingiva-derived mesenchymal stem cell-extracellular vesicles activate schwann cell repair phenotype and promote nerve regeneration. Tissue Eng Part A  2019; 25(11-12): 887-900.
[PMID:  30311853] 
[68] 
Wang F, Yu M, Yan X, et al. Gingiva-derived mesenchymal stem cell-mediated therapeutic approach for bone tissue regeneration. Stem Cells Dev  2011; 20(12): 2093-102.
[http://dx.doi.org/10.1089/scd.2010.0523] [PMID:  21361847] 
[69] 
Xu QC, Wang ZG, Ji QX, et al. Systemically transplanted human gingiva-derived mesenchymal stem cells contributing to bone tissue regeneration. Int J Clin Exp Pathol  2014; 7(8): 4922-9.
[PMID:  25197363] 
[70] 
Carmagnola D, Pellegrini G, Dellavia C, Rimondini L, Varoni E. Tissue engineering in periodontology: Biological mediators for periodontal regeneration. Int J Artif Organs  2019; 42(5): 241-57.
[http://dx.doi.org/10.1177/0391398819828558] [PMID:  30935276] 
[71] 
Yu X, Ge S, Chen S, et al. Human gingiva-derived mesenchymal stromal cells contribute to periodontal regeneration in beagle dogs. Cells Tissues Organs (Print)  2013; 198(6): 428-37.
[http://dx.doi.org/10.1159/000360276] [PMID:  24777155] 
[72] 
Sun W, Wang Z, Xu Q, et al. The treatment of systematically transplanted gingival mesenchymal stem cells in periodontitis in mice. Exp Ther Med  2019; 17(3): 2199-205.
[http://dx.doi.org/10.3892/etm.2019.7165] [PMID:  30783482] 
[73] 
Boink MA, van den Broek LJ, Roffel S, et al. Different wound healing properties of dermis, adipose, and gingiva mesenchymal stromal cells. Wound Repair Regen  2016; 24(1): 100-9.
[http://dx.doi.org/10.1111/wrr.12380] 
[74] 
Li J, Xu SQ, Zhang K, et al. Treatment of gingival defects with gingival mesenchymal stem cells derived from human fetal gingival tissue in a rat model. Stem Cell Res Ther  2018; 9(1): 27.
[http://dx.doi.org/10.1186/s13287-017-0751-7] [PMID:  29402326] 
[75] 
Stuckey DW, Shah K. Stem cell-based therapies for cancer treatment: separating hope from hype. Nat Rev Cancer  2014; 14(10): 683-91.
[http://dx.doi.org/10.1038/nrc3798] [PMID:  25176333] 
[76] 
Bhere D, Shah K. Stem cell-based therapies for cancer. Adv Cancer Res  2015; 127: 159-89.
[http://dx.doi.org/10.1016/bs.acr.2015.04.012] [PMID:  26093900] 
[77] 
Sasportas LS, Kasmieh R, Wakimoto H, et al. Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc Natl Acad Sci USA  2009; 106(12): 4822-7.
[http://dx.doi.org/10.1073/pnas.0806647106] [PMID:  19264968] 
[78] 
Kosaka H, Ichikawa T, Kurozumi K, et al. Therapeutic effect of suicide gene-transferred mesenchymal stem cells in a rat model of glioma. Cancer Gene Ther  2012; 19(8): 572-8.
[http://dx.doi.org/10.1038/cgt.2012.35] [PMID:  22744211] 
[79] 
Auffinger B, Morshed R, Tobias A, Cheng Y, Ahmed AU, Lesniak MS. Drug-loaded nanoparticle systems and adult stem cells: a potential marriage for the treatment of malignant glioma? Oncotarget  2013; 4(3): 378-96.
[http://dx.doi.org/10.18632/oncotarget.937] [PMID:  23594406] 
[80] 
Parker Kerrigan BC, Shimizu Y, Andreeff M, Lang FF. Mesenchymal stromal cells for the delivery of oncolytic viruses in gliomas. Cytotherapy  2017; 19(4): 445-57.
[http://dx.doi.org/10.1016/j.jcyt.2017.02.002] [PMID:  28233640] 
[81] 
Xia L, Peng R, Leng W, et al. TRAIL-expressing gingival-derived mesenchymal stem cells inhibit tumorigenesis of tongue squamous cell carcinoma. J Dent Res  2015; 94(1): 219-28.
[http://dx.doi.org/10.1177/0022034514557815] [PMID:  25391621] 
[82] 
Coccè V, Farronato D, Brini AT, et al. Drug loaded gingival mesenchymal stromal cells (GinPa-MSCs) inhibit in vitro proliferation of oral squamous cell carcinoma. Sci Rep  2017; 7(1): 9376.
[http://dx.doi.org/10.1038/s41598-017-09175-4] [PMID:  28839168] 
[83] 
Ji X, Zhang Z, Han Y, et al. Mesenchymal stem cells derived from normal gingival tissue inhibit the proliferation of oral cancer cells in vitro and in vivo. Int J Oncol  2016; 49(5): 2011-22.
[http://dx.doi.org/10.3892/ijo.2016.3715] [PMID:  27826624] 
[84] 
Ganem D. KSHV and the pathogenesis of Kaposi sarcoma: Listening to human biology and medicine. J Clin Invest  2010; 120(4): 939-49.
[http://dx.doi.org/10.1172/JCI40567] [PMID:  20364091] 
[85] 
Petersen PE. Policy for prevention of oral manifestations in HIV/AIDS: the approach of the WHO Global Oral Health Program. Adv Dent Res  2006; 19(1): 17-20.
[http://dx.doi.org/10.1177/154407370601900105] [PMID:  16672544] 
[86] 
Aškinytė D, Matulionytė R, Rimkevičius A. Oral manifestations of HIV disease: A review. Stomatologija  2015; 17(1): 21-8.
[PMID:  26183854] 
[87] 
Lee MS, Yuan H, Jeon H, et al. Human mesenchymal stem cells of diverse origins support persistent infection with kaposi’s sarcoma-associated herpesvirus and manifest distinct angiogenic, invasive, and transforming phenotypes. MBio  2016; 7(1): e02109-15.
[http://dx.doi.org/10.1128/mBio.02109-15] [PMID:  26814175] 
[88] 
Gholizadeh P, Pormohammad A, Eslami H, Shokouhi B, Fakhrzadeh V, Kafil HS. Oral pathogenesis of Aggregatibacter actinomycetemcomitans. Microb Pathog  2017; 113: 303-11.
[http://dx.doi.org/10.1016/j.micpath.2017.11.001] [PMID:  29117508] 
[89] 
 Mijnendonckx K, Leys N, Mahillon J, et al. Antimicrobial silver: uses, toxicity and potential for resistance. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 2013; 26(4): 609-21. 
[http://dx.doi.org/10.1007/s10534-013-9645-z] 
[90] 
Gordon O, Vig Slenters T, Brunetto PS, et al. Silver coordination polymers for prevention of implant infection: Thiol interaction, impact on respiratory chain enzymes, and hydroxyl radical induction. Antimicrob Agents Chemother  2010; 54(10): 4208-18.
[http://dx.doi.org/10.1128/AAC.01830-09] [PMID:  20660682] 
[91] 
Russell AD, Hugo WB. Antimicrobial activity and action of silver. Prog Med Chem  1994; 31: 351-70.
[http://dx.doi.org/10.1016/S0079-6468(08)70024-9] [PMID:  8029478] 
[92] 
Alexander JW. History of the medical use of silver. Surg Infect (Larchmt)  2009; 10(3): 289-92.
[http://dx.doi.org/10.1089/sur.2008.9941] [PMID:  19566416] 
[93] 
Diniz IM, Chen C, Ansari S, et al. Gingival mesenchymal stem cell (GMSC) delivery system based on RGD-coupled alginate hydrogel with antimicrobial properties: A novel treatment modality for peri-implantitis. J Prosthodont  2016; 25(2): 105-5.
[94] 
Carrion JA, Rajani J, Al Bahrawy M, et al. Osteogenic Potential of Gingival Mesenchymal Stem Cells Over Titanium Machined Surfaces. Int J Oral Maxillofac Implants  2017; 32(5): e249-54.
[http://dx.doi.org/10.11607/jomi.5432] [PMID:  28632254] 
[95] 
Langer R, Vacanti JP. Tissue engineering. Science  1993; 260(5110): 920-6.
[http://dx.doi.org/10.1126/science.8493529] [PMID:  8493529] 
[96] 
Moshaverinia A, Ansari S, Chen C, et al. Co-encapsulation of anti-BMP2 monoclonal antibody and mesenchymal stem cells in alginate microspheres for bone tissue engineering. Biomaterials  2013; 34(28): 6572-9.
[http://dx.doi.org/10.1016/j.biomaterials.2013.05.048] [PMID:  23773817] 
[97] 
Biancone L, Bruno S, Deregibus MC, Tetta C, Camussi G. Therapeutic potential of mesenchymal stem cell-derived microvesicles. Nephrol Dial Transplant  2012; 27(8): 3037-42.
[http://dx.doi.org/10.1093/ndt/gfs168] [PMID:  22851627] 
[98] 
Pashoutan Sarvar D, Shamsasenjan K, Akbarzadehlaleh P. Mesenchymal stem cell-derived exosomes: New opportunity in cell-free therapy. Adv Pharm Bull  2016; 6(3): 293-9.
[http://dx.doi.org/10.15171/apb.2016.041] [PMID:  27766213] 
[99] 
Fierabracci A, Del Fattore A, Luciano R, Muraca M, Teti A, Muraca M. Recent advances in mesenchymal stem cell immunomodulation: the role of microvesicles. Cell Transplant  2015; 24(2): 133-49.
[http://dx.doi.org/10.3727/096368913X675728] [PMID:  24268069] 
[100] 
Maumus M, Jorgensen C, Noël D. Mesenchymal stem cells in regenerative medicine applied to rheumatic diseases: Role of secretome and exosomes. Biochimie  2013; 95(12): 2229-34.
[http://dx.doi.org/10.1016/j.biochi.2013.04.017] [PMID:  23685070] 
[101] 
Yang S, Leong KF, Du Z, Chua CK. The design of scaffolds for use in tissue engineering. Part I. Traditional factors. Tissue Eng  2001; 7(6): 679-89.
[http://dx.doi.org/10.1089/107632701753337645] [PMID:  11749726] 
[102] 
Drury JL, Mooney DJ. Hydrogels for tissue engineering: Scaffold design variables and applications. Biomaterials  2003; 24(24): 4337-51.
[http://dx.doi.org/10.1016/S0142-9612(03)00340-5] [PMID:  12922147] 
[103] 
Moshaverinia A, Chen C, Xu X, et al. Bone regeneration potential of stem cells derived from periodontal ligament or gingival tissue sources encapsulated in RGD-modified alginate scaffold. Tissue Eng Part A  2014; 20(3-4): 611-21.
[PMID:  24070211] 
[104] 
Wee S, Gombotz WR. Protein release from alginate matrices. Adv Drug Deliv Rev  1998; 31(3): 267-85.
[http://dx.doi.org/10.1016/S0169-409X(97)00124-5] [PMID:  10837629] 
[105] 
Lee KY, Mooney DJ. Alginate: Properties and biomedical applications. Prog Polym Sci  2012; 37(1): 106-26.
[http://dx.doi.org/10.1016/j.progpolymsci.2011.06.003] [PMID:  22125349] 
[106] 
Moshaverinia A, Chen C, Akiyama K, et al. Alginate hydrogel as a promising scaffold for dental-derived stem cells: an in vitro study. J Mater Sci Mater Med  2012; 23(12): 3041-51.
[http://dx.doi.org/10.1007/s10856-012-4759-3] [PMID:  22945383] 
[107] 
Ruoslahti E. RGD and other recognition sequences for integrins. Annu Rev Cell Dev Biol  1996; 12: 697-715.
[http://dx.doi.org/10.1146/annurev.cellbio.12.1.697] [PMID:  8970741] 
[108] 
Re’em T, Tsur-Gang O, Cohen S. The effect of immobilized RGD peptide in macroporous alginate scaffolds on TGFbeta1-induced chondrogenesis of human mesenchymal stem cells. Biomaterials  2010; 31(26): 6746-55.
[http://dx.doi.org/10.1016/j.biomaterials.2010.05.025] [PMID:  20542332] 
[109] 
Moshaverinia A, Xu X, Chen C, Akiyama K, Snead ML, Shi S. Dental mesenchymal stem cells encapsulated in an alginate hydrogel co-delivery microencapsulation system for cartilage regeneration. Acta Biomater  2013; 9(12): 9343-50.
[http://dx.doi.org/10.1016/j.actbio.2013.07.023] [PMID:  23891740] 
[110] 
Fawzy El-Sayed KM, Mekhemar MK, Beck-Broichsitter BE, et al. Periodontal regeneration employing gingival margin-derived stem/progenitor cells in conjunction with IL-1ra-hydrogel synthetic extracellular matrix. J Clin Periodontol  2015; 42(5): 448-57.
[http://dx.doi.org/10.1111/jcpe.12401] [PMID:  25875208] 
[111] 
Dash TK, Konkimalla VB. Poly-small je, Ukrainian-caprolactone based formulations for drug delivery and tissue engineering: A review Journal of controlled release. Official Journal of the Controlled Release Society  2012; 158(1): 15-33.
[112] 
Jauregui C, Yoganarasimha S, Madurantakam P. Mesenchymal stem cells derived from healthy and diseased human gingiva support osteogenesis on electrospun polycaprolactone scaffolds. Bioengineering (Basel)  2018; 5(1)E8
[http://dx.doi.org/10.3390/bioengineering5010008] [PMID:  29360752] 
[113] 
Ito M, Shichinohe H, Houkin K, Kuroda S. Application of cell sheet technology to bone marrow stromal cell transplantation for rat brain infarct. J Tissue Eng Regen Med  2017; 11(2): 375-81.
[http://dx.doi.org/10.1002/term.1920] [PMID:  24919680] 
[114] 
Elloumi-Hannachi I, Yamato M, Okano T. Cell sheet engineering: a unique nanotechnology for scaffold-free tissue reconstruction with clinical applications in regenerative medicine. J Intern Med  2010; 267(1): 54-70.
[http://dx.doi.org/10.1111/j.1365-2796.2009.02185.x] [PMID:  20059644] 
[115] 
Kelm JM, Fussenegger M. Scaffold-free cell delivery for use in regenerative medicine. Adv Drug Deliv Rev  2010; 62(7-8): 753-64.
[http://dx.doi.org/10.1016/j.addr.2010.02.003] [PMID:  20153387] 
[116] 
Gaihre B, Uswatta S, Jayasuriya AC. Reconstruction of Craniomaxillofacial Bone Defects Using Tissue-Engineering Strategies with Injectable and Non-Injectable Scaffolds. J Funct Biomater  2017; 8(4)E49
[http://dx.doi.org/10.3390/jfb8040049] [PMID:  29156629] 
[117] 
Atienza-Roca P, Cui X, Hooper GJ, Woodfield TBF, Lim KS. Growth factor delivery systems for tissue engineering and regenerative medicine. Adv Exp Med Biol  2018; 1078: 245-69.
[http://dx.doi.org/10.1007/978-981-13-0950-2_13] [PMID:  30357627] 
[118] 
Clark DA, Coker R. Transforming growth factor-beta (TGF-beta). Int J Biochem Cell Biol  1998; 30(3): 293-8.
[http://dx.doi.org/10.1016/S1357-2725(97)00128-3] [PMID:  9611771] 
[119] 
 Yin F, Cai J, Zen W, et al. Cartilage Regeneration of Adipose- Derived Stem Cells in the TGF-beta1-Immobilized PLGA-Gelatin Scaffold Stem cell reviews and reports 11(3): 453-9.2015;  
[120] 
 Stevens MM, Marini RP, Martin I, et al. FGF-2 enhances TGFbeta1- induced periosteal chondrogenesis Journal of orthopaedic research : official publication of the Orthopaedic Research Society 22(4): 1114-9.2004;   
[121] 
Zhang Y, Zhu Y, Li Y, et al. Long-term engraftment of myogenic progenitors from adipose-derived stem cells and muscle regeneration in dystrophic mice. Hum Mol Genet  2015; 24(21): 6029-40.
[http://dx.doi.org/10.1093/hmg/ddv316] [PMID:  26264578] 
[122] 
Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med  2004; 10(1): 55-63.
[http://dx.doi.org/10.1038/nm979] [PMID:  14702635] 
[123] 
Wang B, Ma X, Zhao L, et al. Injection of basic fibroblast growth factor together with adipose-derived stem cell transplantation: improved cardiac remodeling and function in myocardial infarction. Clin Exp Med  2016; 16(4): 539-50.
[http://dx.doi.org/10.1007/s10238-015-0383-0] [PMID:  26349680] 
[124] 
Ansari S, Chen C, Xu X, et al. Muscle tissue engineering using gingival mesenchymal stem cells encapsulated in alginate hydrogels containing multiple growth factors. Ann Biomed Eng  2016; 44(6): 1908-20.
[http://dx.doi.org/10.1007/s10439-016-1594-6] [PMID:  27009085] 
[125] 
Hsiao C, Tomai M, Glynn J, Palecek SP. Effects of 3D microwell culture on initial fate specification in human embryonic stem cells. AIChE J  2014; 60(4): 1225-35.
[http://dx.doi.org/10.1002/aic.14351] [PMID:  25505348] 
[126] 
He H, He Q, Xu F, Zhou Y, Ye Z, Tan WS. Dynamic formation of cellular aggregates of chondrocytes and mesenchymal stem cells in spinner flask. Cell Prolif  2019; 52(4)e12587
[http://dx.doi.org/10.1111/cpr.12587] [PMID:  31206838] 
[127] 
Costa EC, de Melo-Diogo D, Moreira AF, Carvalho MP, Correia IJ. Spheroids formation on non-adhesive surfaces by liquid overlay technique: Considerations and practical approaches. Biotechnol J  2018; 13(1)
[http://dx.doi.org/10.1002/biot.201700417] [PMID:  29058365] 
[128] 
Yamamoto M, Kawashima N, Takashino N, et al. Three-dimensional spheroid culture promotes odonto/osteoblastic differentiation of dental pulp cells. Arch Oral Biol  2014; 59(3): 310-7.
[http://dx.doi.org/10.1016/j.archoralbio.2013.12.006] [PMID:  24581854] 
[129] 
 Foty R. A simple hanging drop cell culture protocol for generation of 3D spheroids. J Vis Exp JoVE 2011; (51).   
[130] 
Huang GS, Dai LG, Yen BL, Hsu SH. Spheroid formation of mesenchymal stem cells on chitosan and chitosan-hyaluronan membranes. Biomaterials  2011; 32(29): 6929-45.
[http://dx.doi.org/10.1016/j.biomaterials.2011.05.092] [PMID:  21762982] 
[131] 
Cesarz Z, Tamama K. Spheroid culture of mesenchymal stem cells. Stem Cells Int 2016.20169176357
[http://dx.doi.org/10.1155/2016/9176357] [PMID:  26649054] 
[132] 
Subbarayan R, Murugan Girija D, Ranga Rao S. Gingival spheroids possess multilineage differentiation potential. J Cell Physiol  2018; 233(3): 1952-8.
[http://dx.doi.org/10.1002/jcp.25894] [PMID:  28266021] 
[133] 
Lee SI, Ko Y, Park JB. Evaluation of the maintenance of stemness, viability, and differentiation potential of gingiva-derived stem-cell spheroids. Exp Ther Med  2017; 13(5): 1757-64.
[http://dx.doi.org/10.3892/etm.2017.4194] [PMID:  28565764] 
[134] 
Lee SI, Yeo SI, Kim BB, Ko Y, Park JB. Formation of size-controllable spheroids using gingiva-derived stem cells and concave microwells: Morphology and viability tests. Biomed Rep  2016; 4(1): 97-101.
[http://dx.doi.org/10.3892/br.2015.539] [PMID:  26870343] 
[135] 
Rani S, Ryan AE, Griffin MD, et al. Mesenchymal stem cell-derived extracellular vesicles: Toward cell-free therapeutic applications. Mol Ther  2015; 23(5): 812-23.
[136] 
Shi Q, Qian Z, Liu D, et al. GMSC-derived exosomes combined with a chitosan/silk hydrogel sponge accelerates wound healing in a diabetic rat skin defect model. Front Physiol  2017; 8: 904.
[http://dx.doi.org/10.3389/fphys.2017.00904] [PMID:  29163228] 
Rights & Permissions Print Cite
Article Metrics
46
3
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1574888X14666191107100311	Print ISSN 1574-888X
Publisher Name Bentham Science Publisher	Online ISSN 2212-3946
Current Stem Cell Research & Therapy

Gingiva-derived Mesenchymal Stem Cells and Their Potential Applications in Oral and Maxillofacial Diseases

Abstract Play Pause

Related Books

Abstract
