寻找牙周膜干细胞特异性标志物的现状与展望
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摘要
背景:牙周膜干细胞是牙周组织工程中重要的种子细胞,然而干细胞的异质性决定了其在移植治疗中的复杂性和效果的不确定性,寻找特异性表型标志物纯化牙周膜干细胞,发挥其最大的治疗效果是现今科研人员不断尝试的方向。目的:旨在总结牙周膜干细胞异质性的来源和亚群的甄别,指导合适的方法寻找特异性标志物。方法:由第一作者检索中国知网、中国生物医学文献数据库、爱思唯尔数据库、PubMed数据库2013至2018年相关文献。在标题、摘要、关键词中以"periodontal ligament stem cells,heterogeneous,surface marker,subsets,differentiation,isolation,characteristics,extracellular microenvironment"为关键词检索英文数据库;以"牙周膜干细胞,异质性,表面标志物,子集,分化,分离,特征,细胞外微环境"为关键词检索中文数据库。结果与结论:牙周膜干细胞是具有不同间充质细胞来源的异质性群体,现有的基于细胞表面标志物分选牙周膜干细胞的方法,因为抗体的不稳定性以及重叠表达等问题,无法真正准确地鉴别细胞亚群,牙周膜干细胞因为缺少特异性标志物,无法做到真正的识别和分离干性细胞群,未来需要利用蛋白质组学和基因芯片等新技术进一步寻找特异性标志物。
BACKGROUND: Periodontal ligament stem cells are important seed cells in periodontal tissue engineering.However, the heterogeneity of stem cells determines the complexity and uncertainty in transplantation.Researchers are always on the lookout for specific phenotypic markers to purify periodontal ligament stem cells that can exert biggest therapeutic effect.OBJECTIVE: To summarize the sources and subsets of periodontal ligament stem cell heterogeneity to guide appropriate methods for finding specific markers.METHODS: The first author retrieved the relevant literature from 2013 to 2018 in the CNKI, China Biomedical Literature Database, Elsevier Database, and PubMed Database. In the title, abstract, and keyword, the search terms were "periodontal ligament stem cells, heterogeneous,surface marker, subsets, differentiation, isolation, characteristics, extracellular microenvironment" in Chinese and English.RESULTS AND CONCLUSION: Periodontal ligament stem cells are heterogeneous populations with different mesenchymal cell sources.Existing methods for sorting periodontal ligament stem cells based on cell surface markers cannot accurately identify cell subpopulations due to some problems such as antibody instability and overlapping expression. Because of the lack of specific markers, periodontal ligament stem cells cannot truly identify and isolate stem cells. In the future, new technologies such as proteomics and gene chips will be needed to further search for specific markers.
BACKGROUND: Periodontal ligament stem cells are important seed cells in periodontal tissue engineering.However, the heterogeneity of stem cells determines the complexity and uncertainty in transplantation.Researchers are always on the lookout for specific phenotypic markers to purify periodontal ligament stem cells that can exert biggest therapeutic effect.OBJECTIVE: To summarize the sources and subsets of periodontal ligament stem cell heterogeneity to guide appropriate methods for finding specific markers.METHODS: The first author retrieved the relevant literature from 2013 to 2018 in the CNKI, China Biomedical Literature Database, Elsevier Database, and PubMed Database. In the title, abstract, and keyword, the search terms were "periodontal ligament stem cells, heterogeneous,surface marker, subsets, differentiation, isolation, characteristics, extracellular microenvironment" in Chinese and English.RESULTS AND CONCLUSION: Periodontal ligament stem cells are heterogeneous populations with different mesenchymal cell sources.Existing methods for sorting periodontal ligament stem cells based on cell surface markers cannot accurately identify cell subpopulations due to some problems such as antibody instability and overlapping expression. Because of the lack of specific markers, periodontal ligament stem cells cannot truly identify and isolate stem cells. In the future, new technologies such as proteomics and gene chips will be needed to further search for specific markers.
引文
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[4]Hart DA.Why Mesenchymal Stem/Progenitor Cell Heterogeneity in Specific Environments?-Implications for Tissue Engineering Applications Following Injury or Degeneration of Connective Tissues.J Biomedical Science and Engineering.2014;7:526-532.
[5]Thomas GV,Thomas NG,John S,et al.The Scope of Stem Cells in Periodontal Regeneration.J Dent Oral Disord Ther.2015;3(2):1-9.
[6]Chen FM,Gao LN,Tian BM,et al.Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells:a randomized clinical trial.Stem Cell Res Ther.2016;7:33.
[7]Bassir SH,Wisitrasameewong W,Raanan J,et al.Potential for Stem Cell-Based Periodontal Therapy.J Cell Physiol.2016;231(1):50-61.
[8]Menicanin D,Mrozik KM,Wada N,et al.Periodontal-ligamentderived stem cells exhibit the capacity for long-term survival,self-renewal,and regeneration of multiple tissue types in vivo.Stem Cells Dev.2014;23(9):1001-1011.
[9]Seo BM,Miura M,Gronthos S,et al.Investigation of multipotent postnatal stem cells from human periodontal ligament.Lancet.2004;364(9429):149-155.
[10]Wada N,Maeda H,Hasegawa D,et al.Semaphorin 3Ainduces mesenchymal-stem-like properties in human periodontal ligament cells.Stem Cells Dev.2014;23(18):2225-2236.
[11]Zhang H,Liu S,Zhu B,et al.Composite cell sheet for periodontal regeneration:crosstalk between different types of MSCs in cell sheet facilitates complex periodontal-like tissue regeneration.Stem Cell Res Ther.2016;7(1):168.
[12]Mayo V,Sawatari Y,Huang CY,et al.Neural crest-derived dental stem cells--where we are and where we are going.JDent.2014;42(9):1043-1051.
[13]Lee JS,An SY,Kwon IK,et al.Transdifferentiation of human periodontal ligament stem cells into pancreatic cell lineage.Cell Biochem Funct.2014;32(7):605-611.
[14]Saito MT,Salmon CR,Amorim BR,et al.Characterization of highly osteoblast/cementoblast cell clones from a CD105-enriched periodontal ligament progenitor cell population.J Periodontol.2014;85(6):e205-211.
[15]Yoo JH,Lee SM,Bae MK,et al.Effect of orthodontic forces on the osteogenic differentiation of human periodontal ligament stem cells.J Oral Sci.2018;60(3):438-445.
[16]Alvarez R,Lee HL,Wang CY,et al.Characterization of the osteogenic potential of mesenchymal stem cells from human periodontal ligament based on cell surface markers.Int J Oral Sci.2015;7(4):213-219.
[17]Hara ES,Ono M,Eguchi T,et al.mi RNA-720 controls stem cell phenotype,proliferation and differentiation of human dental pulp cells.PLoS One.2013;8(12):e83545.
[18]Tomokiyo A,Hynes K,Ng J,et al.Generation of Neural Crest-Like Cells From Human Periodontal Ligament Cell-Derived Induced Pluripotent Stem Cells.J Cell Physiol.2017;232(2):402-416.
[19]La Noce M,Mele L,Tirino V,et al.Neural crest stem cell population in craniomaxillofacial development and tissue repair.Eur Cell Mater.2014;28:348-357.
[20]Zhu Y,Zhang P,Gu RL,et al.Origin and Clinical Applications of Neural Crest-Derived Dental Stem Cells.Chin J Dent Res.2018;21(2):89-100.
[21]Balic A,Thesleff I.Tissue Interactions Regulating Tooth Development and Renewal.Curr Top Dev Biol.2015;115:157-186.
[22]Balic A.Biology Explaining Tooth Repair and Regeneration:AMini-Review.Gerontology.2018;64(4):382-388.
[23]Martens W,Bronckaers A,Politis C,et al.Dental stem cells and their promising role in neural regeneration:an update.Clin Oral Investig.2013;17(9):1969-1983.
[24]Lima RL,Holanda-Afonso RC,Moura-Neto V,et al.Human dental follicle cells express embryonic,mesenchymal and neural stem cells markers.Arch Oral Biol.2017;73:121-128.
[25]Baggiolini A,Varum S,Mateos JM,et al.Premigratory and migratory neural crest cells are multipotent in vivo.Cell Stem Cell.2015;16(3):314-322.
[26]Ramírez-García L,Cevallos R,Gazarian K.Unveiling and initial characterization of neural crest-like cells in mesenchymal populations from the human periodontal ligament.J Periodontal Res.2017;52(3):609-616.
[27]Iwasaki K,Komaki M,Yokoyama N,et al.Periodontal ligament stem cells possess the characteristics of pericytes.JPeriodontol.2013;84(10):1425-1433.
[28]Bae YK,Kim GH,Lee JC,et al.The Significance of SDF-1α-CXCR4 Axis in in vivo Angiogenic Ability of Human Periodontal Ligament Stem Cells.Mol Cells.2017;40(6):386-392.
[29]De Souza LE,Malta TM,Kashima Haddad S,et al.Mesenchymal Stem Cells and Pericytes:To What Extent Are They Related.Stem Cells Dev.2016;25(24):1843-1852.
[30]Roguljic H,Matthews BG,Yang W,et al.In vivo identification of periodontal progenitor cells.J Dent Res.2013;92(8):709-715.
[31]Wilson KR,Kang IH,Baliga U,et al.Hematopoietic Stem Cells as a Novel Source of Dental Tissue Cells.Sci Rep.2018;8(1):8026.
[32]Nakajima R,Ono M,Hara ES,et al.Mesenchymal stem/progenitor cell isolation from tooth extraction sockets.JDent Res.2014;93(11):1133-1140.
[33]李秋晨,肖苒.人间充质干细胞表面标记分子的研究进展[J].组织工程与重建外科杂志,2013,9(4):229-231.
[34]王冠华.牙周膜干细胞培养及鉴定方法的研究进展[J].医学理论与实践,2014,27(7):869-870.
[35]Tamaki Y,Nakahara T,Ishikawa H,et al.In vitro analysis of mesenchymal stem cells derived from human teeth and bone marrow.Odontology.2013;101(2):121-132.
[36]Tominaga N,Nakahara T,Nasu M,et al.Isolation and characterization of epithelial and myogenic cells by"fishing"for the morphologically distinct cell types in rat primary periodontal ligament cultures.Differentiation.2013;85(3):91-100.
[37]Tran Hle B,Doan VN,Le HT,et al.Various methods for isolation of multipotent human periodontal ligament cells for regenerative medicine.In Vitro Cell Dev Biol Anim.2014;50(7):597-602.
[38]Shinagawa-Ohama R,Mochizuki M,Tamaki Y,et al.Heterogeneous Human Periodontal Ligament-Committed Progenitor and Stem Cell Populations Exhibit a Unique Cementogenic Property Under In Vitro and In Vivo Conditions.Stem Cells Dev.2017;26(9):632-645.
[39]Prateeptongkum E,Klingelh?ffer C,Müller S,et al.Characterization of progenitor cells and stem cells from the periodontal ligament tissue derived from a single person.JPeriodontal Res.2016;51(2):265-272.
[40]Mrozik K,Gronthos S,Shi S,et al.A Method to Isolate,Purify,and Characterize Human Periodontal Ligament Stem Cells.Methods Mol Biol.2017;1537:413-427.
[41]Moritani Y,Usui M,Sano K,et al.Spheroid culture enhances osteogenic potential of periodontal ligament mesenchymal stem cells.J Periodontal Res.2018;53(5):870-882.
[42]Zhou Y,Fan W,Xiao Y.The effect of hypoxia on the stemness and differentiation capacity of PDLC and DPC.Biomed Res Int.2014;2014:890675.
[43]Wu Y,Yang Y,Yang P,et al.The osteogenic differentiation of PDLSCs is mediated through MEK/ERK and p38 MAPKsignalling under hypoxia.Arch Oral Biol.2013;58(10):1357-1368.
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