Int J Stomatol

Int J Stomatol ›› 2023, Vol. 50 ›› Issue (4): 463-471.doi: 10.7518/gjkq.2023064

• Reviews • Previous Articles     Next Articles

Research progress on the stemness maintenance of dental pulp stem cells

Yu Lerong1(),Li Xiangwei1(),Ai Hong2   

  1. 1.Dept. of Stomatology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
    2.Dept. of Stomatology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China
  • Received:2022-09-05 Revised:2022-12-02 Online:2023-07-01 Published:2023-06-21
  • Contact: Xiangwei Li E-mail:404539937@qq.com;lixiangwei@126.com
  • Supported by:
    Natural Science Foundation of Guangdong Province(2022A1515012285);Key Project of Jilin Province Science and Technology Department(20200404132YY)

RichHTML

45

PDF (PC)

435

Abstract:

Dental pulp stem cells (DPSCs) are a unique population of odontogenic undifferentiated mesenchymal stem cells with strong self-renewal ability and multi-lineage differentiation potential existing in the dental pulp tissue. They could differentiate into osteoblasts, chondrocytes, odontoblasts, adipocytes, nerve cells, muscle cells, and hepatocytes under specific stimulation conditions, providing a novel clinical idea for their application in the treatment of various tissue defects and repairs. However, in the process of passage and expansion in vitro, DPSCs inevitably exhibit decreased stemness, such as slowed proliferation rate, cell senescence, and pluripotency decline, which seriously impede their application in tissue engineering. How to overcome these deficiencies and maintain the stemness of DPSCs have received extensive attention in tissue engineering research. In this article, the research progress on the significance, methods (including low-temperature preservation, culture dimensions, hypoxic environment, application of cytokines, etc.), and molecular mechanisms of stemness maintenance of DPSCs was reviewed.

Key words: dental pulp stem cells, stemness, stemness maintenance, stemness regulation mechanism

CLC Number: 

  • R 78

TrendMD: 
1 Cui DX, Li HY, Wan M, et al. The origin and identification of mesenchymal stem cells in teeth: from odontogenic to non-odontogenic[J]. Curr Stem Cell Res Ther, 2018, 13(1): 39-45.
2 Ogata K, Moriyama M, Matsumura-Kawashima M, et al. The therapeutic potential of secreted factors from dental pulp stem cells for various diseases[J]. Biomedicines, 2022, 10(5): 1049.
3 Zhang JL, Lu XH, Feng GJ, et al. Chitosan scaffolds induce human dental pulp stem cells to neural differentiation: potential roles for spinal cord injury therapy[J]. Cell Tissue Res, 2016, 366(1): 129-142.
4 Shimojima C, Takeuchi H, Jin SJ, et al. Conditioned medium from the stem cells of human exfoliated deciduous teeth ameliorates experimental autoimmune encephalomyelitis[J]. J Immunol, 2016, 196(10): 4164-4171.
5 Ullah I, Park JM, Kang YH, et al. Transplantation of human dental pulp-derived stem cells or differentia-ted neuronal cells from human dental pulp-derived stem cells identically enhances regeneration of the injured peripheral nerve[J]. Stem Cells Dev, 2017, 26(17): 1247-1257.
6 Fernandes TL, Shimomura K, Asperti A, et al. Development of a novel large animal model to eva-luate human dental pulp stem cells for articular cartilage treatment[J]. Stem Cell Rev Rep, 2018, 14(5): 734-743.
7 Syed-Picard FN, Du YQ, Lathrop KL, et al. Dental pulp stem cells: A new cellular resource for corneal stromal regeneration[J]. Stem Cells Transl Med, 2015, 4(3): 276-285.
8 Datta I, Bhadri N, Shahani P, et al. Functional reco-very upon human dental pulp stem cell transplantation in a diabetic neuropathy rat model[J]. Cytothe-rapy, 2017, 19(10): 1208-1224.
9 Barros MA, Martins JF, Maria DA, et al. Immature dental pulp stem cells showed renotropic and pericyte-like properties in acute renal failure in rats[J]. Cell Med, 2015, 7(3): 95-108.
10 Cao XF, Jin SZ, Sun L, et al. Therapeutic effects of hepatocyte growth factor-overexpressing dental pulp stem cells on liver cirrhosis in a rat model[J]. Sci Rep, 7(1): 15812.
11 贺莹. 体外连续培养人牙髓干细胞干性特征改变的相关研究[D]. 西安: 第四军医大学, 2015.
He Y. Changing of stemness during serial passage of hDPSCs in vitro [D]. Xi’an: The Fourth Military Medical University, 2015.
12 Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors[J]. Cell, 2006, 126(4): 663-676.
13 Ferro F, Spelat R, D’Aurizio F, et al. Dental pulp stem cells differentiation reveals new insights in Oct4A dynamics[J]. PLoS One, 2012, 7(7): e41774.
14 Liu L, Wei X, Ling JQ, et al. Expression pattern of Oct-4, Sox2, and c-Myc in the primary culture of human dental pulp derived cells[J]. J Endod, 2011, 37(4): 466-472.
15 Rodas-Junco BA, Villicaña C. Dental pulp stem cells: current advances in isolation, expansion and preservation[J]. Tissue Eng Regen Med, 2017, 14(4): 333-347.
16 Pilbauerová N, Soukup T, Suchánková Kleplová T, et al. Enzymatic isolation, amplification and characterization of dental pulp stem cells[J]. Folia Biol (Praha), 2019, 65(3): 124-133.
17 Huynh NC, Le SH, Doan VN, et al. Simplified conditions for storing and cryopreservation of dental pulp stem cells[J]. Arch Oral Biol, 2017, 84: 74-81.
18 Pilbauerova N, Schmidt J, Soukup T, et al. The effects of cryogenic storage on human dental pulp stem cells[J]. Int J Mol Sci, 2021, 22(9): 4432.
19 Lee SY, Huang GW, Shiung JN, et al. Magnetic cryopreservation for dental pulp stem cells[J]. Cells Tissues Organs, 2012, 196(1): 23-33.
20 Gioventù S, Andriolo G, Bonino F, et al. A novel method for banking dental pulp stem cells[J]. Transfus Apher Sci, 2012, 47(2): 199-206.
21 Yan M, Nada OA, Kluwe L, et al. Expansion of human dental pulp cells in vitro under different cryopreservation conditions[J]. In Vivo, 2020, 34(5): 2363-2370.
22 Wang W, Yan M, Aarabi G, et al. Cultivation of cryopreserved human dental pulp stem cells-a new approach to maintaining dental pulp tissue[J]. Int J Mol Sci, 2022, 23(19): 11485.
23 Shuai Y, Liao L, Su XX, et al. Melatonin treatment improves mesenchymal stem cells therapy by preserving stemness during long-term in vitro expansion[J]. Theranostics, 2016, 6(11): 1899-1917.
24 Yin QL, Xu N, Xu DS, et al. Comparison of senescence-related changes between three- and two-dimensional cultured adipose-derived mesenchymal stem cells[J]. Stem Cell Res Ther, 2020, 11(1): 226.
25 Zhang SY, Buttler-Buecher P, Denecke B, et al. A comprehensive analysis of human dental pulp cell spheroids in a three-dimensional pellet culture system[J]. Arch Oral Biol, 2018, 91: 1-8.
26 Ryu NE, Lee SH, Park H. Spheroid culture system methods and applications for mesenchymal stem cells[J]. Cells, 2019, 8(12): 1620.
27 Cesarz Z, Tamama K. Spheroid culture of mesenchymal stem cells[J]. Stem Cells Int, 2016, 2016: 1-11.
28 Tietze S, Kräter M, Jacobi A, et al. Spheroid culture of mesenchymal stromal cells results in morphor-heological properties appropriate for improved microcirculation[J]. Adv Sci (Weinh), 2019, 6(8):1802104.
29 Chan YH, Lee YC, Hung CY, et al. Three-dimensional spheroid culture enhances multipotent diffe-rentiation and stemness capacities of human dental pulp-derived mesenchymal stem cells by modula-ting MAPK and NF-kB signaling pathways[J]. Stem Cell Rev Rep, 2021, 17(5): 1810-1826.
30 李驰宇, 郭雨薇, 纳静, 等. 细胞形状调控人牙髓干细胞干性维持及其机制研究[J]. 医用生物力学, 2021, 36(S1): 1.
Li CY, Guo YW, Na J, et al. Mechanism research on regulating stemness of human dental pulp stem cells by cell shape[J]. J Med Biomechan, 2021, 36(S1): 1.
31 Yu CY, Boyd NM, Cringle SJ, et al. Oxygen distribution and consumption in rat lower incisor pulp[J]. Arch Oral Biol, 2002, 47(7): 529-536.
32 Estrada JC, Albo C, Benguría A, et al. Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis[J]. Cell Death Differ, 2012, 19(5): 743-755.
33 Laksana K, Sooampon S, Pavasant P, et al. Cobalt chloride enhances the stemness of human dental pulp cells[J]. J Endod, 2017, 43(5): 760-765.
34 Chen YJ, Zhao Q, Yang X, et al. Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth[J]. Cell Stress Chaperones, 2019, 24(3): 527-538.
35 Bhandi S, Al Kahtani A, Mashyakhy M, et al. Modulation of the dental pulp stem cell secretory profile by hypoxia induction using cobalt chloride[J]. J Pers Med, 2021, 11(4): 247.
36 Meng HF, Wei F, Ge ZQ, et al. Long-term hypoxia inhibits the passage-dependent stemness decrease and senescence increase of human dental pulp stem cells[J]. Tissue Cell, 2022, 76: 101819.
37 Zhou YH, Fan W, Xiao Y. The effect of hypoxia on the stemness and differentiation capacity of PDLC and DPC[J]. Biomed Res Int, 2014, 2014: 890675.
38 Iida K, Takeda-Kawaguchi T, Tezuka Y, et al. Hypoxia enhances colony formation and proliferation but inhibits differentiation of human dental pulp cells[J]. Arch Oral Biol, 2010, 55(9): 648-654.
39 Ahmed NE, Murakami M, Kaneko S, et al. The effects of hypoxia on the stemness properties of human dental pulp stem cells (DPSCs)[J]. Sci Rep, 2016, 6: 35476.
40 Mossahebi-Mohammadi M, Quan MY, Zhang JS, et al. FGF signaling pathway: a key regulator of stem cell pluripotency[J]. Front Cell Dev Biol, 2020, 8: 79.
41 Shimabukuro Y, Ueda M, Ozasa M, et al. Fibroblast growth factor-2 regulates the cell function of human dental pulp cells[J]. J Endod, 2009, 35(11): 1529-1535.
42 Yang JW, Zhang YF, Sun ZY, et al. Dental pulp tissue engineering with bFGF-incorporated silk fibroin scaffolds[J]. J Biomater Appl, 2015, 30(2): 221-229.
43 Tsutsumi S, Shimazu A, Miyazaki K, et al. Retention of multilineage differentiation potential of me-senchymal cells during proliferation in response to FGF[J]. Biochem Biophys Res Commun, 2001, 288(2): 413-419.
44 Morito A, Kida Y, Suzuki K, et al. Effects of basic fibroblast growth factor on the development of the stem cell properties of human dental pulp cells[J]. Arch Histol Cytol, 2009, 72(1): 51-64.
45 Jauković A, Kukolj T, Trivanović D, et al. Modula-ting stemness of mesenchymal stem cells from exfoliated deciduous and permanent teeth by IL-17 and bFGF[J]. J Cell Physiol, 2021, 236(11): 7322-7341.
46 Osathanon T, Nowwarote N, Pavasant P. Basic fibroblast growth factor inhibits mineralization but indu-ces neuronal differentiation by human dental pulp stem cells through a FGFR and PLCγ signaling pathway[J]. J Cell Biochem, 2011, 112(7): 1807-1816.
47 Qian J, Jiayuan W, Wenkai J, et al. Basic fibroblastic growth factor affects the osteogenic differentiation of dental pulp stem cells in a treatment-dependent manner[J]. Int Endod J, 2015, 48(7): 690-700.
48 Fakhry A, Ratisoontorn C, Vedhachalam C, et al. Effects of FGF-2/-9 in calvarial bone cell cultures: differentiation stage-dependent mitogenic effect, inverse regulation of BMP-2 and noggin, and enhancement of osteogenic potential[J]. Bone, 2005, 36(2): 254-266.
49 Mullen AC, Wrana JL. TGF-β family signaling in embryonic and somatic stem-cell renewal and diffe-rentiation[J]. Cold Spring Harb Perspect Biol, 2017, 9(7): a022186.
50 Salkın H, Gönen ZB, Ergen E, et al. Effects of TGF-β1 overexpression on biological characteristics of human dental pulp-derived mesenchymal stromal cells[J]. Int J Stem Cells, 2019, 12(1): 170-182.
51 Yamasaki S, Taguchi Y, Shimamoto A, et al. Generation of human induced pluripotent stem (Ips) cells in serum- and feeder-free defined culture and TGF-Β1 regulation of pluripotency[J]. PLoS One, 2014, 9(1): e87151.
52 熊梦琳, 吴龙, 马丽, 等. 转化生长因子-β2促进牙髓干细胞增殖和分化的作用研究[J]. 国际口腔医学杂志, 2021, 48(6): 635-639.
Xiong ML, Wu L, Ma L, et al. Role of transforming growth factor-β2 in promoting the proliferation and differentiation of dental pulp stem cells[J]. Int J Stomatol, 2021, 48(6): 635-639.
53 Liu L, Wu LJ, Wei X, et al. Induced overexpression of Oct4A in human dental pulp cells enhances pluripotency and multilineage differentiation capability[J]. Stem Cells Dev, 2015, 24(8): 962-972.
54 Zhang XF, Zhang J, Wang T, et al. Esrrb activates Oct4 transcription and sustains self-renewal and pluripotency in embryonic stem cells[J]. J Biol Chem, 2008, 283(51): 35825-35833.
55 Huang C, Hu FW, Yu CH, et al. Concurrent expression of Oct4 and Nanog maintains mesenchymal stem-like property of human dental pulp cells[J]. Int J Mol Sci, 2014, 15(10): 18623-18639.
56 Hara ES, Ono M, Eguchi T, et al. miRNA-720 controls stem cell phenotype, proliferation and differentiation of human dental pulp cells[J]. PLoS One, 2013, 8(12): e83545.
57 Sun DG, Xin BC, Wu D, et al. miR-140-5p-media-ted regulation of the proliferation and differentiation of human dental pulp stem cells occurs through the lipopolysaccharide/toll-like receptor 4 signaling pa-thway[J]. Eur J Oral Sci, 2017, 125(6): 419-425.
58 Qiu ZL, Lin SH, Hu XG, et al. Involvement of miR-146a-5p/neurogenic locus notch homolog protein 1 in the proliferation and differentiation of STRO-1+ human dental pulp stem cells[J]. Eur J Oral Sci, 2019, 127(4): 294-303.
59 吕红兵, 郑碧琼, 雷丽珊, 等. 人牙髓干细胞及非牙髓干细胞中微小RNA表达谱比较研究[J]. 中国实用口腔科杂志, 2014, 7(3): 146-150.
Lü HB, Zheng BQ, Lei LS, et al. Comparison of miRNAs expression profiles between human dental pulp stem cells and non-stem cells[J]. Chin J Pract Stomatol, 2014, 7(3): 146-150.
60 Li JD, Rao ZL, Zhao YM, et al. A decellularized matrix hydrogel derived from human dental pulp promotes dental pulp stem cell proliferation, migration, and induced multidirectional differentiation in vitro [J]. J Endod, 2020, 46(10): 1438-1447.e5.
61 Niloy KK, Gulfam M, Compton KB, et al. Methacrylated hyaluronic acid-based hydrogels maintain stemness in human dental pulp stem cells[J]. Regen Eng Transl Med, 2020, 6(3): 262-272.
62 Zhang LL, Xia DS, Wang C, et al. Pleiotrophin attenuates the senescence of dental pulp stem cells[J]. Oral Dis, 2023, 29(1): 195-205.
63 Al-Habib M, Yu ZD, Huang GT. Small molecules affect human dental pulp stem cell properties via multiple signaling pathways[J]. Stem Cells Dev, 2013, 22(17): 2402-2413.
64 Lin CY, Chin YT, Kuo PJ, et al. 2, 3, 5, 4’-tetrahydroxystilbene-2-O‑β‑glucoside potentiates self-renewal of human dental pulp stem cells via the AMPK/ERK/SIRT1 axis[J]. Int Endod J, 2018, 51(10): 1159-1170.
65 Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development[J]. Science, 1999, 284(5415): 770-776.
66 Zhang C, Chang J, Sonoyama W, et al. Inhibition of human dental pulp stem cell differentiation by Notch signaling[J]. J Dent Res, 2008, 87(3): 250-255.
67 Wang XF, He F, Tan YH, et al. Inhibition of Delta1 promotes differentiation of odontoblasts and inhibits proliferation of human dental pulp stem cell in vitro [J]. Arch Oral Biol, 2011, 56(9): 837-845.
68 关丽娜. 低氧环境下Notch信号通路对人牙髓干细胞增殖和分化的影响[D]. 西安: 第四军医大学, 2015.
Guan LN. Effects of Notch signaling pathway on human dental pulp stem cells’ proliferation and diffe-rentiation in the hypoxia environment[D]. Xi’an: The Fourth Military Medical University, 2015.
69 Reya T, Clevers H. Wnt signalling in stem cells and cancer[J]. Nature, 2005, 434(7035): 843-850.
70 Uribe-Etxebarria V, Agliano A, Unda F, et al. Wnt signaling reprograms metabolism in dental pulp stem cells[J]. J Cell Physiol, 2019, 234(8): 13068-13082.
71 Kornsuthisopon C, Photichailert S, Nowwarote N, et al. Wnt signaling in dental pulp homeostasis and dentin regeneration[J]. Arch Oral Biol, 2022, 134: 105322.
72 Uribe-Etxebarria V, Cell Biology and Histology Department Faculty of Medicine and Nursing University of the Basque Country (UPV/EHU) Barrio Sarriena S/N Leioa Spain, Luzuriaga J, et al. Notch/Wnt cross-signalling regulates stemness of dental pulp stem cells through expression of neural crest and core pluripotency factors[J]. ECM, 2017, 34: 249-270.
73 Sato N, Meijer L, Skaltsounis L, et al. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor[J]. Nat Med, 2004, 10(1): 55-63.
74 Chang YC, Chang MC, Chen YJ, et al. Basic fibroblast growth factor regulates gene and protein expression related to proliferation, differentiation, and matrix production of human dental pulp cells[J]. J Endod, 2017, 43(6): 936-942.
75 Luo LH, Zhang YN, Chen HY, et al. Effects and mechanisms of basic fibroblast growth factor on the proliferation and regenerative profiles of cryopreserved dental pulp stem cells[J]. Cell Prolif, 2021, 54(2): e12969.
76 Liu F, Huang X, Luo ZH, et al. Hypoxia-activated PI3K/Akt inhibits oxidative stress via the regulation of reactive oxygen species in human dental pulp cells[J]. Oxid Med Cell Longev, 2019, 2019: 659-5189.
77 Skandalis SS, Karalis TT, Chatzopoulos A, et al. Hyaluronan-CD44 axis orchestrates cancer stem cell functions[J]. Cell Signal, 2019, 63: 109377.
78 Umemura N, Ohkoshi E, Tajima M, et al. Hyaluronan induces odontoblastic differentiation of dental pulp stem cells via CD44[J]. Stem Cell Res Ther, 2016, 7(1): 135.
79 Zhang WW, Shen JL, Zhang S, et al. Silencing integrin α6 enhances the pluripotency-differentiation transition in human dental pulp stem cells[J]. Oral Dis, 2022, 28(3): 711-722.
80 Cucco C, Zhang ZC, Botero TM, et al. SCF/C-kit signaling induces self-renewal of dental pulp stem cells[J]. J Endod, 2020, 46(9S): S56-S62.
[1] Fu Hengyi,Wang Chenglin. Research progress on serum-free culture methods of human dental pulp stem cells and cell characterization [J]. Int J Stomatol, 2022, 49(2): 220-226.
[2] Xiong Menglin,Wu Long,Ma Li,Zhao Jin. Role of transforming growth factor-β2 in promoting the proliferation and differentiation of dental pulp stem cells [J]. Int J Stomatol, 2021, 48(6): 635-639.
[3] Yang Maobin1, Zeng Qian2. Regenerative endodontics: a new treatment modality for pulp regeneration [J]. Inter J Stomatol, 2016, 43(5): 495-499.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[2] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[3] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[4] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[5] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[6] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[7] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[8] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[9] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[10] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .