诱导多能性干细胞的获取及其在口腔组织再生中的作用及应用
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摘要
背景:干细胞是再生医学的基础,诱导多能性干细胞的出现开启了干细胞研究的新篇章,被认为是近10年干细胞研究的重大突破。将成人体细胞重新编程为多能干细胞解决了伦理学和免疫排斥等矛盾,实现了个性化的基于细胞的疗法,革新了疾病的研究方式和治疗策略。近年来的研究发现诱导多能干细胞在口腔再生医学领域也具有极大的应用价值,虽然此研究还处于初级阶段,但诱导多能性干细胞在牙齿组织再生中已表现出巨大的潜力。目的:对诱导多能性干细胞的来源、诱导条件及其在口腔组织医学中的应用和研究等方面作一综述。方法:由第一作者以"诱导多能干细胞、口腔组织再生、成人体细胞";"iPSCs,dental tissue regeneration,adult somatic cells"为关键词,检索从2010年至2018年PubMed,Medline,中国知网,万方等数据库上与诱导多能性干细胞和口腔组织工程医学相关的文献,语言设为中文和英文,排除与文章研究要求无关及重复性的文章,纳入符合标准的62篇文献进行综述。结果与结论:诱导多能性干细胞的研究开启了干细胞研究的新方向,它来源广泛,但从口腔组织获取有其独特的优势。此外,诱导多能性干细胞避免了阻碍胚胎干细胞发展的免疫干扰和伦理问题。现有的文献已证实诱导多能干细胞能分化成牙体组织,牙周软组织及牙槽骨组织,在口腔组织再生应用方面有广阔的应用前景。
BACKGROUND: The research of regenerative medicine is based on stem cells. The emergence of induced pluripotent stem cells blazes a trail for stem cell research, which is considered to be a major breakthrough in stem cell research in the last decade. Reprogramming adult somatic cells into a pluripotent stem cell-like state avoids dilemmas regarding ethics and immune rejection, which helps achieve personalized cell-based therapy and revolutionize disease research methods and treatment strategies. Recent studies have found that induced pluripotent stem cells have great application values in the field of dental regenerative medicine. Although this research is still at its infancy, induced pluripotent stem cells have shown huge potential in tooth tissue regeneration. OBJECTIVE: To review the main progress about induced pluripotent stem cell sources and induction conditions as well as its related application in oral tissue medicine. METHODS: A computer-based online retrieval of PubMed and CNKI was performed to search relevant articles about induced pluripotent stem cells and oral tissue engineering published from 2010 to 2018, with the keywords of "induced pluripotent stem cell(iPSCs), dental tissue regeneration, adult somatic cells" in English and Chinese, respectively. After removal of repetitive or irrelevant articles, 62 articles finally met the criteria for review. RESULTS AND CONCLUSION: Studies on induced pluripotent stem cells open a new direction for stem cell research. Although the source of induced pluripotent stem cells is extensive, the origins of oral tissue appear to have unique advantages over other tissues. In addition, induced pluripotent stem cells bypass numerous ethical and legal concerns that have hindered embryonic stem cell research. Existing studies have shown that induced pluripotent stem cells can differentiate into dental tissues, periodontal tissue and alveolar bone tissue, which have potential utility in oral tissue regeneration.
BACKGROUND: The research of regenerative medicine is based on stem cells. The emergence of induced pluripotent stem cells blazes a trail for stem cell research, which is considered to be a major breakthrough in stem cell research in the last decade. Reprogramming adult somatic cells into a pluripotent stem cell-like state avoids dilemmas regarding ethics and immune rejection, which helps achieve personalized cell-based therapy and revolutionize disease research methods and treatment strategies. Recent studies have found that induced pluripotent stem cells have great application values in the field of dental regenerative medicine. Although this research is still at its infancy, induced pluripotent stem cells have shown huge potential in tooth tissue regeneration. OBJECTIVE: To review the main progress about induced pluripotent stem cell sources and induction conditions as well as its related application in oral tissue medicine. METHODS: A computer-based online retrieval of PubMed and CNKI was performed to search relevant articles about induced pluripotent stem cells and oral tissue engineering published from 2010 to 2018, with the keywords of "induced pluripotent stem cell(iPSCs), dental tissue regeneration, adult somatic cells" in English and Chinese, respectively. After removal of repetitive or irrelevant articles, 62 articles finally met the criteria for review. RESULTS AND CONCLUSION: Studies on induced pluripotent stem cells open a new direction for stem cell research. Although the source of induced pluripotent stem cells is extensive, the origins of oral tissue appear to have unique advantages over other tissues. In addition, induced pluripotent stem cells bypass numerous ethical and legal concerns that have hindered embryonic stem cell research. Existing studies have shown that induced pluripotent stem cells can differentiate into dental tissues, periodontal tissue and alveolar bone tissue, which have potential utility in oral tissue regeneration.
引文
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[34]Chang YC, Li WC, Twu NF, et al. Induction of dental pulp-derived induced pluripotent stem cells in the absence of c-Myc for differentiation into neuron-like cells. J Chin Med Assoc. 2014; 77(12):618-625.
[35]Chu Z, Niu B, Zhu H, et al. PRMT5 enhances generation of induced pluripotent stem cells from dairy goat embryonic fibroblasts via down-regulation of p53. Cell Proliferation. 2015;48(1):29.
[36]Hou P, Li Y, Zhang X, et al. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science. 2013;341(6146):651-654.
[37]Esteban MA, Wang T, Qin B, et al. Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell.2010;6(1):71.
[38]Wang T, Chen K, Zeng X, et al. The histone demethylases jhdm1a/1b enhance somatic cell reprogramming in a Vitamin-C-dependent manner. Cell Stem Cell. 2011;9(6):575-587.
[39]Gafni O, Weinberger L, Mansour AA, et al. Corrigendum:derivation of novel human ground state naive pluripotent stem cells. Nature. 2013;504(7479):282.
[40]Zou XY, Yang HY, Yu Z, et al. Establishment of transgene-free induced pluripotent stem cells reprogrammed from human stem cells of apical papilla for neural differentiation. Stem Cell Res Ther. 2012;3(5):43.
[41]Li L, Wang Y, Lin M, et al. Augmented BMPRIA-mediated BMP signaling in cranial neural crest lineage leads to cleft palate formation and delayed tooth differentiation. PLoS One. 2013;8(6):e66107.
[42]Komada Y, Yamane T, Kadota D, et al. Origins and properties of dental,thymic, and bone marrow mesenchymal cells and their stem cells.PLo S One. 2011;7(11):e46436.
[43]RothováM, PeterkováR, Tucker A S. Fate map of the dental mesenchyme:dynamic development of the dental papilla and follicle.Dev Biol. 2012;366(2):244.
[44]Otsu K, Kishigami R, Oikawa-Sasaki A, et al. Differentiation of induced pluripotent stem cells into dental mesenchymal cells. Stem Cells Dev.2012;21(7):1156.
[45]Wen Y, Wang F, Zhang W, et al. Application of induced pluripotent stem cells in generation of a tissue-engineered tooth-like structure.Tissue EngPart A. 2012;18(15-16):1677.
[46]Cai J, Zhang Y, Liu P, et al. Generation of tooth-like structures from integration-free human urine induced pluripotent stem cells. Cell Regen(Lond). 2013;2(1):6.
[47]Liu P, Zhang Y, Chen S, et al. Application of iPS cells in dental bioengineering and beyond. Stem Cell Rev. 2014;10(5):663-670.
[48]Arakaki M, Ishikawa M, Nakamura T, et al. Role of epithelial-stem cell interactions during dental cell differentiation. J Biol Chem. 2012;287(13):10590-601.
[49]Ning F, Guo Y, Tang J, et al. Differentiation of mouse embryonic stem cells into dental epithelial-like cells induced by ameloblasts serum-free conditioned medium. Biochem Biophys Res Commun. 2010;394(2):342.
[50]Liu L, Liu Y, Zhang J, et al. Ameloblasts serum-free conditioned medium:bone morphogenic protein 4-induced odontogenic differentiation of mouse induced pluripotent stem cells. J Tissue Eng Regen Med. 2013;10(6):466-474.
[51]Farooqi OA, Wehler CJ, Gibson G, et al. Appropriate recall interval for periodontal maintenance:a systematic review. J Evid Based Dent Pract. 2015;15(4):171.
[52]Chien KH, Chang YL, Wang M L, et al. Promoting induced pluripotent stem cell-driven biomineralization and periodontal regeneration in rats with maxillary-molar defects using injectable BMP-6 hydrogel. Sci Rep.2018;8(1):114..
[53]Luo L, He Y, Wang X, et al. Potential roles of dental pulp stem cells in neural regeneration and repair. Stem Cells Int. 2018;2018:1731289.
[54]Cheng PP, Liu XC, Ma PF, et al. Mesenchymal stem cells derived from induced pluripotent stem cells combined with low-dose rapamycin induced islet allograft tolerance via suppressing Th1 and enhancing regulatory T cell differentiation. Stem Cells Dev. 2015;24(15):1793-1804.
[55]Zhang J, Guan J, Niu X, et al. Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. J Transl Med. 2015;13(1):49.
[56]Hynes K, Menicanin D, Mrozik K, et al. Generation of functional mesenchymal stem cells from different induced pluripotent stem cell lines. Stem Cells Dev. 2014;23(10):1084-1096.
[57]Hynes K, Menicanin D, Han J, et al. Mesenchymal stem cells from iPS cells facilitate periodontal regeneration. J Dent Res. 2013;92(9):833-839.
[58]Egusa H, Kayashima H, Miura J, et al. Comparative analysis of mouse-induced pluripotent stem cells and mesenchymal stem cells during osteogenic differentiation in vitro. Stem Cells Dev. 2014;23(18):2156-2169.
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[2]Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell.2007;2(12):3081-3089.
[3]Maherali N, Sridharan R, Xie W, et al. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell. 2007;1(1):55-70.
[4]Bar-Nur O, Russ H, Efrat S, et al. Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell. 2011;9(1):17-23.
[5]Yamanaka S. Induced pluripotent stem cells:past, present, and future.Cell Stem Cell. 2012;10(6):678-684.
[6]Hargus G, Cooper O, Deleidi M, et al. Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats.Proc Natl Acad Sci U S A. 2010;107(36):15921-15926.
[7]Soldner F, Laganière J, Cheng AW, et al. Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell. 2011;146(2):318-331.
[8]Sebastiano V, Maeder ML, Angstman JF, et al. In situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases. Stem Cells. 2011;29(11):1717-1726.
[9]Spence JR, Mayhew CN, Rankin SA, et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature.2011;470(7332):105-109.
[10]Takebe T, Sekine K, Enomura M, et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature.2013;499(7459):481-484.
[11]Wang L, Wang L, Huang W, et al. Generation of integration-free neural progenitor cells from cells in human urine. Nature Methods. 2013;10(1):84-89.
[12]Liebau S, Mahaddalkar PU, Kestler HA, et al. A hierarchy in reprogramming capacity in different tissue microenvironments:what we know and what we need to know. Stem Cells Dev. 2013; 22(5):695-706.
[13]Hynes K, Menichanin D, Bright R, et al. Induced pluripotent stem cells:a new frontier for stem cells in dentistry. J Dent Res. 2015;94(11):1508.
[14]Yan X, Qin H, Qu C, et al. iPS cells reprogrammed from human mesenchymal-like stem/progenitor cells of dental tissue origin. Stem Cells Dev. 2010;19(4):469.
[15]Wada N, Wang B, Lin NH, et al. Induced pluripotent stem cell lines derived from human gingival fibroblasts and periodontal ligament fibroblasts. J Periodont Res. 2011;46(4):438-447.
[16]Oda Y, Yoshimura Y, Ohnishi H, et al. Induction of pluripotent stem cells from human third molar mesenchymal stromal cells. J Biol Chem.2010;285(38):29270-29278.
[17]Nomura Y, Ishikawa M, Yashiro Y, et al. Human periodontal ligament fibroblasts are the optimal cell source for induced pluripotent stem cells.Histochem Cell Biol. 2012;137(6):719-732.
[18]Beltr?o-Braga PC, Pignatari GC, Maiorka PC, et al. Feeder-free derivation of induced pluripotent stem cells from human immature dental pulp stem cells. Cell Transplantation. 2011;20(11-12):1707.
[19]Dambrot C, Van d PS, Van ZL, et al. Polycistronic lentivirus induced pluripotent stem cells from skin biopsies after long term storage, blood outgrowth endothelial cells and cells from milk teeth. Differentiation.2013;85(3):101.
[20]Miyoshi K, Tsuji D, Kudoh K, et al. Generation of human induced pluripotent stem cells from oral mucosa. J Biosci Bioeng. 2010; 110(3):345-350.
[21]Tamaoki N, Takahashi K, Tanaka T, et al. Dental pulp cells for induced pluripotent stem cell banking. J Dent Res. 2010;89(8):773-778.
[22]Yoo CH, Na HJ, Lee DS, et al. Endothelial progenitor cells from human dental pulp-derived iPS cells as a therapeutic target for ischemic vascular diseases. Biomaterials. 2013;34(33):8149-8160.
[23]Chen J, Lin M, Foxe JJ, et al. Transcriptome comparison of human neurons generated using induced pluripotent stem cells derived from dental pulp and skin fibroblasts. PLoS One. 2013;8(10):e75682.
[24]Warren L, Manos PD, Ahfeldt T, et al. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell. 2010;7(5):618.
[25]Xue Y, Cai X, Wang L, et al. Generating a non-integrating human induced pluripotent stem cell bank from urine-derived cells. PLoS One.2013;8(8):e70573.
[26]Zhou T, Benda C, Duzinger S, et al. Generation of induced pluripotent stem cells from urine. J Am Soc Nephrol. 2011;22(7):1221-1228.
[27]Linta L, Stockmann M, Kleinhans KN, et al. Rat embryonic fibroblasts improve reprogramming of human keratinocytes into induced pluripotent stem cells. Stem Cells Dev. 2012;21(6):965-976.
[28]Gareri J, Koren G. Prenatal hair development:implications for drug exposure determination. Forensic Sci Int. 2010;196(1):27-31.
[29]Piao Y, Hung SS, Lim S Y, et al. Efficient generation of integration-free human induced pluripotent stem cells from keratinocytes by simple transfection of episomal vectors. Stem Cells Transl Med. 2014; 3(7):787-791.
[30]Wang J, Gu Q, Hao J, et al. Generation of induced pluripotent stem cells with high efficiency from human umbilical cord blood mononuclear cells. Genomics Proteomics Bioinformatics. 2013; 11(5):304.
[31]Garreta E, Melo E, Navajas D, et al. Low oxygen tension enhances the generation of lung progenitor cells from mouse embryonic and induced pluripotent stem cells. Physiol Rep. 2014;2(7):e12075.
[32]Bae D, Mondragonteran P, Hernandez D, et al. Hypoxia enhances the generation of retinal progenitor cells from human induced pluripotent and embryonic stem cells. Stem Cells Dev. 2012;21(21):1344-1355.
[33]Li HY, Chien Y, Chen YJ, et al. Reprogramming induced pluripotent stem cells in the absence of c-Myc for differentiation into hepatocyte-like cells. Biomaterials. 2011;32(26):5994.
[34]Chang YC, Li WC, Twu NF, et al. Induction of dental pulp-derived induced pluripotent stem cells in the absence of c-Myc for differentiation into neuron-like cells. J Chin Med Assoc. 2014; 77(12):618-625.
[35]Chu Z, Niu B, Zhu H, et al. PRMT5 enhances generation of induced pluripotent stem cells from dairy goat embryonic fibroblasts via down-regulation of p53. Cell Proliferation. 2015;48(1):29.
[36]Hou P, Li Y, Zhang X, et al. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science. 2013;341(6146):651-654.
[37]Esteban MA, Wang T, Qin B, et al. Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell.2010;6(1):71.
[38]Wang T, Chen K, Zeng X, et al. The histone demethylases jhdm1a/1b enhance somatic cell reprogramming in a Vitamin-C-dependent manner. Cell Stem Cell. 2011;9(6):575-587.
[39]Gafni O, Weinberger L, Mansour AA, et al. Corrigendum:derivation of novel human ground state naive pluripotent stem cells. Nature. 2013;504(7479):282.
[40]Zou XY, Yang HY, Yu Z, et al. Establishment of transgene-free induced pluripotent stem cells reprogrammed from human stem cells of apical papilla for neural differentiation. Stem Cell Res Ther. 2012;3(5):43.
[41]Li L, Wang Y, Lin M, et al. Augmented BMPRIA-mediated BMP signaling in cranial neural crest lineage leads to cleft palate formation and delayed tooth differentiation. PLoS One. 2013;8(6):e66107.
[42]Komada Y, Yamane T, Kadota D, et al. Origins and properties of dental,thymic, and bone marrow mesenchymal cells and their stem cells.PLo S One. 2011;7(11):e46436.
[43]RothováM, PeterkováR, Tucker A S. Fate map of the dental mesenchyme:dynamic development of the dental papilla and follicle.Dev Biol. 2012;366(2):244.
[44]Otsu K, Kishigami R, Oikawa-Sasaki A, et al. Differentiation of induced pluripotent stem cells into dental mesenchymal cells. Stem Cells Dev.2012;21(7):1156.
[45]Wen Y, Wang F, Zhang W, et al. Application of induced pluripotent stem cells in generation of a tissue-engineered tooth-like structure.Tissue EngPart A. 2012;18(15-16):1677.
[46]Cai J, Zhang Y, Liu P, et al. Generation of tooth-like structures from integration-free human urine induced pluripotent stem cells. Cell Regen(Lond). 2013;2(1):6.
[47]Liu P, Zhang Y, Chen S, et al. Application of iPS cells in dental bioengineering and beyond. Stem Cell Rev. 2014;10(5):663-670.
[48]Arakaki M, Ishikawa M, Nakamura T, et al. Role of epithelial-stem cell interactions during dental cell differentiation. J Biol Chem. 2012;287(13):10590-601.
[49]Ning F, Guo Y, Tang J, et al. Differentiation of mouse embryonic stem cells into dental epithelial-like cells induced by ameloblasts serum-free conditioned medium. Biochem Biophys Res Commun. 2010;394(2):342.
[50]Liu L, Liu Y, Zhang J, et al. Ameloblasts serum-free conditioned medium:bone morphogenic protein 4-induced odontogenic differentiation of mouse induced pluripotent stem cells. J Tissue Eng Regen Med. 2013;10(6):466-474.
[51]Farooqi OA, Wehler CJ, Gibson G, et al. Appropriate recall interval for periodontal maintenance:a systematic review. J Evid Based Dent Pract. 2015;15(4):171.
[52]Chien KH, Chang YL, Wang M L, et al. Promoting induced pluripotent stem cell-driven biomineralization and periodontal regeneration in rats with maxillary-molar defects using injectable BMP-6 hydrogel. Sci Rep.2018;8(1):114..
[53]Luo L, He Y, Wang X, et al. Potential roles of dental pulp stem cells in neural regeneration and repair. Stem Cells Int. 2018;2018:1731289.
[54]Cheng PP, Liu XC, Ma PF, et al. Mesenchymal stem cells derived from induced pluripotent stem cells combined with low-dose rapamycin induced islet allograft tolerance via suppressing Th1 and enhancing regulatory T cell differentiation. Stem Cells Dev. 2015;24(15):1793-1804.
[55]Zhang J, Guan J, Niu X, et al. Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. J Transl Med. 2015;13(1):49.
[56]Hynes K, Menicanin D, Mrozik K, et al. Generation of functional mesenchymal stem cells from different induced pluripotent stem cell lines. Stem Cells Dev. 2014;23(10):1084-1096.
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