Int J Stomatol ›› 2022, Vol. 49 ›› Issue (3): 255-262.doi: 10.7518/gjkq.2022043

• Stem Cells and Regenerative Medicine • Previous Articles     Next Articles

Research progress on dental stem cells in the treatment of nervous system diseases

Cai Yunzhu(),Zhu Shu,Liu Yao,Chen Xu.()   

  1. Dept. of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University; Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110002, China
  • Received:2021-06-18 Revised:2021-12-13 Online:2022-05-01 Published:2022-05-09
  • Contact: Xu. Chen;
  • Supported by:
    National Natural Science Foundation of China(81900963);the Open Fund of Key Laboratory of Ministry of Education(zyzx1909)


Nervous system diseases include central and peripheral nervous system diseases, such as spinal cord injury, Alzheimer’s disease, stroke, chronic cerebral ischemia, and sciatic nerve injury. No effective treatment method is available for these diseases. Mesenchymal stem cells (MSCs) have the potential for self-renewal and multi-lineage differentiation and have gradually become a new strategy for the treatment of neurological diseases. Dental stem cells are derived from the embryonic neural crest and are homologous to nervous tissues. Compared with MSCs from other tissues, dental stem cells are easier to obtain and have less damages to the donor and less susceptibility to immune rejection. This article reviews the research advances of application of dental stem cells in tissue repair and regeneration of nervous system diseases.

Key words: dental stem cell, nervous system disease, tissue repair, nerve regeneration

CLC Number: 

  • Q 813

1 Wang DR, Wang YH, Tian WD, et al. Advances of tooth-derived stem cells in neural diseases treatments and nerve tissue regeneration[J]. Cell Prolif, 2019, 52(3): e12572.
2 Abuarqoub D, Aslam N, Almajali B, et al. Neuro-regenerative potential of dental stem cells: a concise review[J]. Cell Tissue Res, 2020, 382(2): 267-279.
3 Gronthos S, Mankani M, Brahim J, et al. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo[J]. Proc Natl Acad Sci U S A, 2000, 97(25): 13625-13630.
4 Miura M, Gronthos S, Zhao MR, et al. SHED: stem cells from human exfoliated deciduous teeth[J]. Proc Natl Acad Sci U S A, 2003, 100(10): 5807-5812.
5 Seo BM, Miura M, Gronthos S, et al. Investigation of multipotent postnatal stem cells from human perio-dontal ligament[J]. Lancet, 2004, 364(9429): 149-155.
6 Honda MJ, Imaizumi M, Tsuchiya S, et al. Dental follicle stem cells and tissue engineering[J]. J Oral Sci, 2010, 52(4): 541-552.
7 Sonoyama W, Liu Y, Fang DJ, et al. Mesenchymal stem cell-mediated functional tooth regeneration in swine[J]. PLoS One, 2006, 1: e79.
8 Su WT, Shih YA, Ko CS. Effect of chitosan conduit under a dynamic culture on the proliferation and neural differentiation of human exfoliated deciduous teeth stem cells[J]. J Tissue Eng Regen Med, 2016, 10(6): 507-517.
9 Huang CY, Pelaez D, Dominguez-Bendala J, et al. Plasticity of stem cells derived from adult periodontal ligament[J]. Regen Med, 2009, 4(6): 809-821.
10 Morsczeck C, Völlner F, Saugspier M, et al. Comparison of human dental follicle cells (DFCs) and stem cells from human exfoliated deciduous teeth (SHED) after neural differentiation in vitro[J]. Clin Oral Investig, 2010, 14(4): 433-440.
11 Kolar MK, Itte VN, Kingham PJ, et al. The neurotrophic effects of different human dental mesenchymal stem cells[J]. Sci Rep, 2017, 7(1): 12605.
12 Jiang Y, Gong FL, Zhao GB, et al. Chrysin suppressed inflammatory responses and the inducible nitric oxide synthase pathway after spinal cord injury in rats[J]. Int J Mol Sci, 2014, 15(7): 12270-12279.
13 Yamamoto A, Sakai K, Matsubara K, et al. Multifaceted neuro-regenerative activities of human dental pulp stem cells for functional recovery after spinal cord injury[J]. Neurosci Res, 2014, 78: 16-20.
14 Yang C, Li XH, Sun L, et al. Potential of human dental stem cells in repairing the complete transection of rat spinal cord[J]. J Neural Eng, 2017, 14(2): 026005.
15 Guo SW, Redenski I, Landau S, et al. Prevascularized scaffolds bearing human dental pulp stem cells for treating complete spinal cord injury[J]. Adv Healthc Mater, 2020, 9(20): e2000974.
16 Nicola FDC, Marques MR, Odorcyk F, et al. Neuroprotector effect of stem cells from human exfoliated deciduous teeth transplanted after traumatic spinal cord injury involves inhibition of early neuronal apoptosis[J]. Brain Res, 2017, 1663: 95-105.
17 刘露, 翟启明, 张青, 等. 脱落乳牙牙髓干细胞治疗大鼠脊髓损伤的实验研究[J]. 实用口腔医学杂志, 2020, 36(3): 437-442.
Liu L, Zhai QM, Zhang Q, et al. An experimental study of stem cells from human exfoliated deciduous teeth in the treatment of spinal cord injury in rats[J]. J Pract Stomatol, 2020, 36(3): 437-442.
18 De Berdt P, Bottemanne P, Bianco J, et al. Stem cells from human apical papilla decrease neuro-inflammation and stimulate oligodendrocyte progenitor differentiation via activin-a secretion[J]. Cell Mol Life Sci, 2018, 75(15): 2843-2856.
19 Kandalam S, De Berdt P, Ucakar B, et al. Human dental stem cells of the apical papilla associated to BDNF-loaded pharmacologically active microcarriers (PAMs) enhance locomotor function after spinal cord injury[J]. Int J Pharm, 2020, 587: 119685.
20 Wang FX, Jia YL, Liu JJ, et al. Dental pulp stem cells promote regeneration of damaged neuron cells on the cellular model of Alzheimer’s disease[J]. Cell Biol Int, 2017, 41(6): 639-650.
21 Fu J, Zhang XM, Ouyang YJ, et al. Therapeutic potential of dental pulp stem cell transplantation in a rat model of Alzheimer’s disease[J]. Neural Regen Res, 2021, 16(5): 893-898.
22 Ahmed Nel-M, Murakami M, Hirose Y, et al. Therapeutic potential of dental pulp stem cell secretome for Alzheimer’s disease treatment: an in vitro study[J]. Stem Cells Int, 2016, 2016: 8102478.
23 Mita T, Furukawa-Hibi Y, Takeuchi H, et al. Conditioned medium from the stem cells of human dental pulp improves cognitive function in a mouse model of Alzheimer’s disease[J]. Behav Brain Res, 2015, 293: 189-197.
24 Kanafi M, Majumdar D, Bhonde R, et al. Midbrain cues dictate differentiation of human dental pulp stem cells towards functional dopaminergic neurons[J]. J Cell Physiol, 2014, 229(10): 1369-1377.
25 Gnanasegaran N, Govindasamy V, Mani V, et al. Neuroimmunomodulatory properties of DPSCs in an in vitro model of Parkinson’s disease[J]. IUBMB Life, 2017, 69(9): 689-699.
26 Narbute K, Piļipenko V, Pupure J, et al. Intranasal administration of extracellular vesicles derived from human teeth stem cells improves motor symptoms and normalizes tyrosine hydroxylase expression in the substantia nigra and striatum of the 6-hydroxydopamine-treated rats[J]. Stem Cells Transl Med, 2019, 8(5): 490-499.
27 Zhang N, Lu XJ, Wu SC, et al. Intrastriatal transplantation of stem cells from human exfoliated deciduous teeth reduces motor defects in Parkinsonian rats[J]. Cytotherapy, 2018, 20(5): 670-686.
28 GBD 2016 DALYs and HALE Collaborators. Glo-bal, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016[J]. Lancet, 2017, 390(10100): 1260-1344.
29 Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view[J]. Trends Neurosci, 1999, 22(9): 391-397.
30 Allen CL, Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke[J]. Int J Stroke, 2009, 4(6): 461-470.
31 Zhang XM, Zhou YL, Li HL, et al. Transplanted dental pulp stem cells migrate to injured area and express neural markers in a rat model of cerebral ische-mia[J]. Cell Physiol Biochem, 2018, 45(1): 258-266.
32 Song M, Lee JH, Bae J, et al. Human dental pulp stem cells are more effective than human bone marrow-derived mesenchymal stem cells in cerebral ischemic injury[J]. Cell Transplant, 2017, 26(6): 1001-1016.
33 徐婉婷. 比较牙髓干细胞和牙周膜干细胞的神经向分化能力以及对脑缺血模型的治疗效果[D]. 合肥: 安徽医科大学, 2020.
Xu WT. Comparison of the differentiation of dental pulp stem cells and periodontal ligament stem cells into neuron-like cells and the treatment effect on focal cerebral ischemia[D]. Hefei: Anhui Medical University, 2020.
34 Sowa K, Nito C, Nakajima M, et al. Impact of dental pulp stem cells overexpressing hepatocyte growth factor after cerebral ischemia/reperfusion in rats[J]. Mol Ther Methods Clin Dev, 2018, 10: 281-290.
35 Mead B, Logan A, Berry M, et al. Concise review: dental pulp stem cells: a novel cell therapy for retinal and central nervous system repair[J]. Stem Cells, 2017, 35(1): 61-67.
36 Mead B, Hill LJ, Blanch RJ, et al. Mesenchymal stromal cell-mediated neuroprotection and functional preservation of retinal ganglion cells in a rodent model of glaucoma[J]. Cytotherapy, 2016, 18(4): 487-496.
37 Cen LP, Ng TK, Liang JJ, et al. Human periodontal ligament-derived stem cells promote retinal ganglion cell survival and axon regeneration after optic nerve injury[J]. Stem Cells, 2018, 36(6): 844-855.
38 Otani T, Ochiai D, Masuda H, et al. The neurorestora-tive effect of human amniotic fluid stem cells on the chronic phase of neonatal hypoxic-ischemic encepha-lopathy in mice[J]. Pediatr Res, 2019, 85(1): 97-104.
39 Tatebayashi K, Takagi T, Fujita M, et al. Adipose-derived stem cell therapy inhibits the deterioration of cerebral infarction by altering macrophage kine-tics[J]. Brain Res, 2019, 1712: 139-150.
40 Namioka T, Namioka A, Sasaki M, et al. Intravenous infusion of mesenchymal stem cells promotes functional recovery in a rat model of chronic cerebral infarction[J]. J Neurosurg, 2018: 1-8.
41 Zhu S, Min DY, Zeng JH, et al. Transplantation of stem cells from human exfoliated deciduous teeth decreases cognitive impairment from chronic cerebral ischemia by reducing neuronal apoptosis in rats[J]. Stem Cells Int, 2020, 2020: 6393075.
42 Chiu HY, Lin CH, Hsu CY, et al. IGF-1R+ dental pulp stem cells enhanced neuroplasticity in hypoxia-ischemia model[J]. Mol Neurobiol, 2017, 54(10): 8225-8241.
43 Sanen K, Martens W, Georgiou M, et al. Engineered neural tissue with Schwann cell differentiated human dental pulp stem cells: potential for peripheral nerve repair[J]. J Tissue Eng Regen Med, 2017, 11(12): 3362-3372.
44 Carnevale G, Pisciotta A, Riccio M, et al. Human dental pulp stem cells expressing STRO-1, c-kit and CD34 markers in peripheral nerve regeneration[J]. J Tissue Eng Regen Med, 2018, 12(2): e774-e785.
45 Luo LH, He Y, Jin L, et al. Application of bioactive hydrogels combined with dental pulp stem cells for the repair of large gap peripheral nerve injuries[J]. Bioact Mater, 2021, 6(3): 638-654.
46 Hata M, Omi M, Kobayashi Y, et al. Transplantation of human dental pulp stem cells ameliorates diabetic polyneuropathy in streptozotocin-induced diabetic nude mice: the role of angiogenic and neurotrophic factors[J]. Stem Cell Res Ther, 2020, 11(1): 236.
47 Sasaki R, Matsumine H, Watanabe Y, et al. Electrophysiologic and functional evaluations of regenera-ted facial nerve defects with a tube containing dental pulp cells in rats[J]. Plast Reconstr Surg, 2014, 134(5): 970-978.
48 Saez DM, Sasaki RT, Martins DO, et al. Rat facial nerve regeneration with human immature dental pulp stem cells[J]. Cell Transplant, 2019, 28(12): 1573-1584.
49 陈彪, 张睿, 张文娟, 等. 牙髓干细胞对兔面神经损伤的修复作用及其机制[J]. 吉林大学学报(医学版), 2018, 44(3): 504-509, 695.
Chen B, Zhang R, Zhang WJ, et al. Repair effect of dental pulp stem cells on facial nerve injury in rabbits and its mechanism[J]. J Jilin Univ (Med Ed), 2018, 44(3): 504-509, 695.
50 Pereira LV, Bento RF, Cruz DB, et al. Stem cells from human exfoliated deciduous teeth (SHED) differentiate in vivo and promote facial nerve regeneration[J]. Cell Transplant, 2019, 28(1): 55-64.
51 Sung DK, Chang YS, Ahn SY, et al. Optimal route for human umbilical cord blood-derived mesenchymal stem cell transplantation to protect against neonatal hyperoxic lung injury: gene expression profiles and histopathology[J]. PLoS One, 2015, 10(8): e0135574.
52 Khojasteh A, Motamedian SR, Rad MR, et al. Polymeric vs hydroxyapatite-based scaffolds on dental pulp stem cell proliferation and differentiation[J]. World J Stem Cells, 2015, 7(10): 1215-1221.
53 Zhao YH, Wang YJ, Gong JH, et al. Chitosan degradation products facilitate peripheral nerve regeneration by improving macrophage-constructed microenvironments[J]. Biomaterials, 2017, 134: 64-77.
54 Li XH, Yang C, Li L, et al. A therapeutic strategy for spinal cord defect: human dental follicle cells combined with aligned PCL/PLGA electrospun material[J]. Biomed Res Int, 2015, 2015: 197183.
55 Li R, Li YY, Wu YQ, et al. Heparin-poloxamer thermosensitive hydrogel loaded with bFGF and NGF enhances peripheral nerve regeneration in diabetic rats[J]. Biomaterials, 2018, 168: 24-37.
56 Rao ZL, Lin T, Qiu S, et al. Decellularized nerve matrix hydrogel scaffolds with longitudinally oriented and size-tunable microchannels for peripheral nerve regeneration[J]. Mater Sci Eng C Mater Biol Appl, 2021, 120: 111791.
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