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Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

Stem Cells from Human Exfoliated Deciduous Teeth and their Promise as Preventive and Therapeutic Strategies for Neurological Diseases and Injuries

Author(s): Lingyi Huang, Zizhuo Zheng, Ding Bai and Xianglong Han*

Volume 17, Issue 6, 2022

Published on: 18 February, 2022

Page: [527 - 536] Pages: 10

DOI: 10.2174/1574888X17666211229155533

Price: $65

Abstract

Stem cells from human exfoliated deciduous teeth (SHEDs) are relatively easy to isolate from exfoliated deciduous teeth, which are obtained via dental therapy as biological waste. SHEDs originate from the embryonic neural crest, and therefore, have considerable potential for neurogenic differentiation. Currently, an increasing amount of research is focused on the therapeutic applications of SHEDs in neurological diseases and injuries. In this article, we summarize the biological characteristics of SHEDs and the potential role of SHEDs and their derivatives, including conditioned medium from SHEDs and the exosomes they secrete, in the prevention and treatment of neurological diseases and injuries.

Keywords: Human exfoliated deciduous teeth, stem cells, conditioned medium, exosomes, neurological diseases and injuries, therapy.

Graphical Abstract

[1]
Gronthos S, Brahim J, Li W, et al. Stem cell properties of human dental pulp stem cells. J Dent Res 2002; 81(8): 531-5.
[http://dx.doi.org/10.1177/154405910208100806] [PMID: 12147742]
[2]
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]
[3]
Kerkis I, Kerkis A, Dozortsev D, et al. Isolation and characterization of a population of immature dental pulp stem cells expressing OCT-4 and other embryonic stem cell markers. Cells Tissues Organs 2006; 184(3-4): 105-16.
[http://dx.doi.org/10.1159/000099617] [PMID: 17409736]
[4]
Achilleos A, Trainor PA. Neural crest stem cells: Discovery, properties and potential for therapy. Cell Res 2012; 22(2): 288-304.
[http://dx.doi.org/10.1038/cr.2012.11] [PMID: 22231630]
[5]
Martens W, Wolfs E, Struys T, Politis C, Bronckaers A, Lambrichts I. Expression pattern of basal markers in human dental pulp stem cells and tissue. Cells Tissues Organs 2012; 196(6): 490-500.
[http://dx.doi.org/10.1159/000338654] [PMID: 22739146]
[6]
Arthur A, Rychkov G, Shi S, Koblar SA, Gronthos S. Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues. Stem Cells 2008; 26(7): 1787-95.
[http://dx.doi.org/10.1634/stemcells.2007-0979] [PMID: 18499892]
[7]
Nosrat IV, Smith CA, Mullally P, Olson L, Nosrat CA. Dental pulp cells provide neurotrophic support for dopaminergic neurons and differentiate into neurons in vitro; implications for tissue engineering and repair in the nervous system. Eur J Neurosci 2004; 19(9): 2388-98.
[http://dx.doi.org/10.1111/j.0953-816X.2004.03314.x] [PMID: 15128393]
[8]
Yalvac ME, Rizvanov AA, Kilic E, et al. Potential role of dental stem cells in the cellular therapy of cerebral ischemia. Curr Pharm Des 2009; 15(33): 3908-16.
[http://dx.doi.org/10.2174/138161209789649439] [PMID: 19938343]
[9]
Zhang N, Lu X, Wu S, et al. Intrastriatal transplantation of stem cells from human exfoliated deciduous teeth reduces motor defects in Parkinsonian rats. Cytotherapy 2018; 20(5): 670-86.
[http://dx.doi.org/10.1016/j.jcyt.2018.02.371] [PMID: 29576501]
[10]
Inoue T, Sugiyama M, Hattori H, Wakita H, Wakabayashi T, Ueda M. Stem cells from human exfoliated deciduous tooth-derived conditioned medium enhance recovery of focal cerebral ischemia in rats. Tissue Eng Part A 2013; 19(1-2): 24-9.
[http://dx.doi.org/10.1089/ten.tea.2011.0385] [PMID: 22839964]
[11]
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. Brain Res 2017; 1663: 95-105.
[http://dx.doi.org/10.1016/j.brainres.2017.03.015] [PMID: 28322752]
[12]
Liu H, Gronthos S, Shi S. 2006; Dental pulp stem cells. Methods Enzymol 419: 99-113.
[http://dx.doi.org/10.1016/S0076-6879(06)19005-9]
[13]
Suchánek J, Visek B, Soukup T, et al. Stem cells from human exfoliated deciduous teeth-isolation, long term cultivation and phenotypical analysis. Acta Med (Hradec Kralove) 2010; 53(2): 93-9.
[http://dx.doi.org/10.14712/18059694.2016.66] [PMID: 20672745]
[14]
Yamamoto A, Sakai K, Matsubara K, Kano F, Ueda M. Multifaceted neuro-regenerative activities of human dental pulp stem cells for functional recovery after spinal cord injury. Neurosci Res 2014; 78: 16-20.
[http://dx.doi.org/10.1016/j.neures.2013.10.010] [PMID: 24252618]
[15]
Kanafi MM, Ramesh A, Gupta PK, Bhonde RR. Influence of hypoxia, high glucose, and low serum on the growth kinetics of mesenchymal stem cells from deciduous and permanent teeth. Cells Tissues Organs 2013; 198(3): 198-208.
[http://dx.doi.org/10.1159/000354901] [PMID: 24192068]
[16]
Yin Z, Wang Q, Li Y, Wei H, Shi J, Li A. A novel method for banking stem cells from human exfoliated deciduous teeth: lentiviral TERT immortalization and phenotypical analysis. Stem Cell Res Ther 2016; 7: 50.
[http://dx.doi.org/10.1186/s13287-016-0309-0] [PMID: 27044500]
[17]
Yao S, Tan L, Chen H, Huang X, Zhao W, Wang Y. Potential research tool of stem cells from human exfoliated deciduous teeth: Lentiviral Bmi-1 immortalization with EGFP marker. Stem Cells Int 2019; 2019: 3526409.
[http://dx.doi.org/10.1155/2019/3526409] [PMID: 30984268]
[18]
Werle SB, Chagastelles P, Pranke P, Casagrande L. Hypoxia upregulates the expression of the pluripotency markers in the stem cells from human deciduous teeth. Clin Oral Investig 2019; 23(1): 199-207.
[http://dx.doi.org/10.1007/s00784-018-2427-9] [PMID: 29626259]
[19]
Chen Y, Zhao Q, Yang X, Yu X, Yu D, Zhao W. Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth. Cell Stress Chaperones 2019; 24(3): 527-38.
[http://dx.doi.org/10.1007/s12192-019-00981-5] [PMID: 30806897]
[20]
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]
[21]
Heng BC, Lim LW, Wu W, Zhang C. An overview of protocols for the neural induction of dental and oral stem cells in vitro. Tissue Eng Part B Rev 2016; 22(3): 220-50.
[http://dx.doi.org/10.1089/ten.teb.2015.0488] [PMID: 26757369]
[22]
Sakai K, Yamamoto A, Matsubara K, et al. Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms. J Clin Invest 2012; 122(1): 80-90.
[PMID: 22133879]
[23]
Wang J, Wang X, Sun Z, et al. Stem cells from human-exfoliated deciduous teeth can differentiate into dopaminergic neuron-like cells. Stem Cells Dev 2010; 19(9): 1375-83.
[http://dx.doi.org/10.1089/scd.2009.0258] [PMID: 20131979]
[24]
Feng X, Xing J, Feng G, et al. Age-dependent impaired neurogenic differentiation capacity of dental stem cell is associated with Wnt/β-catenin signaling. Cell Mol Neurobiol 2013; 33(8): 1023-31.
[http://dx.doi.org/10.1007/s10571-013-9965-0] [PMID: 24043508]
[25]
Vismara I, Papa S, Rossi F, Forloni G, Veglianese P. Current options for cell therapy in spinal cord injury. Trends Mol Med 2017; 23(9): 831-49.
[http://dx.doi.org/10.1016/j.molmed.2017.07.005] [PMID: 28811172]
[26]
Taghipour Z, Karbalaie K, Kiani A, et al. Transplantation of undifferentiated and induced human exfoliated deciduous teeth-derived stem cells promote functional recovery of rat spinal cord contusion injury model. Stem Cells Dev 2012; 21(10): 1794-802.
[http://dx.doi.org/10.1089/scd.2011.0408] [PMID: 21970342]
[27]
Nicola FC, Rodrigues LP, Crestani T, et al. Human dental pulp stem cells transplantation combined with treadmill training in rats after traumatic spinal cord injury. Braz J Med Biol Res 2016; 49(9): e5319.
[http://dx.doi.org/10.1590/1414-431x20165319] [PMID: 27509306]
[28]
Nicola F, Marques MR, Odorcyk F, et al. Stem cells from human exfoliated deciduous teeth modulate early astrocyte response after spinal cord contusion. Mol Neurobiol 2019; 56(1): 748-60.
[http://dx.doi.org/10.1007/s12035-018-1127-4] [PMID: 29796991]
[29]
Prado C, Fratini P, de Sá Schiavo Matias G, et al. Combination of stem cells from deciduous teeth and electroacupuncture for therapy in dogs with chronic spinal cord injury: A pilot study. Res Vet Sci 2019; 123: 247-51.
[http://dx.doi.org/10.1016/j.rvsc.2019.01.011] [PMID: 30703615]
[30]
Fujii H, Matsubara K, Sakai K, et al. Dopaminergic differentiation of stem cells from human deciduous teeth and their therapeutic benefits for Parkinsonian rats. Brain Res 2015; 1613: 59-72.
[http://dx.doi.org/10.1016/j.brainres.2015.04.001] [PMID: 25863132]
[31]
Koehler RC, Yang ZJ, Lee JK, Martin LJ. Perinatal hypoxic-ischemic brain injury in large animal models: Relevance to human neonatal encephalopathy. J Cereb Blood Flow Metab 2018; 38(12): 2092-111.
[http://dx.doi.org/10.1177/0271678X18797328] [PMID: 30149778]
[32]
Yamagata M, Yamamoto A, Kako E, et al. Human dental pulp-derived stem cells protect against hypoxic-ischemic brain injury in neonatal mice. Stroke 2013; 44(2): 551-4.
[http://dx.doi.org/10.1161/STROKEAHA.112.676759] [PMID: 23238858]
[33]
Kitase Y, Sato Y, Ueda K, et al. A Novel Treatment with stem cells from human exfoliated deciduous teeth for hypoxic-ischemic encephalopathy in neonatal rats. Stem Cells Dev 2020; 29(2): 63-74.
[http://dx.doi.org/10.1089/scd.2019.0221] [PMID: 31801412]
[34]
Liu Q, Wang X, Yi S. Pathophysiological changes of physical barriers of peripheral nerves after injury. Front Neurosci 2018; 12: 597.
[http://dx.doi.org/10.3389/fnins.2018.00597] [PMID: 30210280]
[35]
Navarro X. Functional evaluation of peripheral nerve regeneration and target reinnervation in animal models: A critical overview. Eur J Neurosci 2016; 43(3): 271-86.
[http://dx.doi.org/10.1111/ejn.13033] [PMID: 26228942]
[36]
Beigi MH, Ghasemi-Mobarakeh L, Prabhakaran MP, et al. In vivo integration of poly(ε-caprolactone)/gelatin nanofibrous nerve guide seeded with teeth derived stem cells for peripheral nerve regeneration. J Biomed Mater Res A 2014; 102(12): 4554-67.
[PMID: 24677613]
[37]
Sasaki R, Aoki S, Yamato M, et al. Tubulation with dental pulp cells promotes facial nerve regeneration in rats. Tissue Eng Part A 2008; 14(7): 1141-7.
[http://dx.doi.org/10.1089/ten.tea.2007.0157] [PMID: 18593355]
[38]
Sasaki R, Aoki S, Yamato M, et al. PLGA artificial nerve conduits with dental pulp cells promote facial nerve regeneration. J Tissue Eng Regen Med 2011; 5(10): 823-30.
[http://dx.doi.org/10.1002/term.387] [PMID: 22002926]
[39]
Pereira LV, Bento RF, Cruz DB, et al. Stem cells from Human Exfoliated Deciduous teeth (SHED) differentiate in vivo and promote facial nerve regeneration. Cell Transplant 2019; 28(1): 55-64.
[http://dx.doi.org/10.1177/0963689718809090] [PMID: 30380914]
[40]
Yamaguchi S, Shibata R, Yamamoto N, et al. Dental pulp-derived stem cell conditioned medium reduces cardiac injury following ischemia-reperfusion. Sci Rep 2015; 6(5): 16295.
[http://dx.doi.org/10.1038/srep16295] [PMID: 26542315]
[41]
Shimojima C, Takeuchi H, Jin S, et al. Conditioned medium from the stem cells of human exfoliated deciduous teeth ameliorates experimental autoimmune encephalomyelitis. J Immunol 2016; 196(10): 4164-71.
[http://dx.doi.org/10.4049/jimmunol.1501457] [PMID: 27053763]
[42]
Fujiwara T, Yoshioka S, Yoshioka T, Ushiyama I, Horikoshi H. Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats. Diabetes 1988; 37(11): 1549-58.
[http://dx.doi.org/10.2337/diab.37.11.1549] [PMID: 3053303]
[43]
Asadi-Golshan R, Razban V, Mirzaei E, et al. Sensory and motor behavior evidences supporting the usefulness of conditioned medium from dental pulp-derived stem cells in spinal cord injury in rats. Asian Spine J 2018; 12(5): 785-93.
[http://dx.doi.org/10.31616/asj.2018.12.5.785] [PMID: 30213159]
[44]
Matsubara K, Matsushita Y, Sakai K, et al. Secreted ectodomain of sialic acid-binding Ig-like lectin-9 and monocyte chemoattractant protein-1 promote recovery after rat spinal cord injury by altering macrophage polarity. J Neurosci 2015; 35(6): 2452-64.
[http://dx.doi.org/10.1523/JNEUROSCI.4088-14.2015] [PMID: 25673840]
[45]
Shin T, Ahn M, Moon C, Kim S, Sim KB. Alternatively activated macrophages in spinal cord injury and remission: another mechanism for repair? Mol Neurobiol 2013; 47(3): 1011-9.
[http://dx.doi.org/10.1007/s12035-013-8398-6] [PMID: 23321790]
[46]
Serdar M, Kempe K, Rizazad M, et al. Early pro-inflammatory microglia activation after inflammation-sensitized hypoxic-ischemic brain injury in neonatal rats. Front Cell Neurosci 2019; 13: 237.
[http://dx.doi.org/10.3389/fncel.2019.00237] [PMID: 31178702]
[47]
Qin C, Fan WH, Liu Q, et al. Fingolimod protects against ischemic white matter damage by modulating microglia toward M2 polarization via STAT3 pathway. Stroke 2017; 48(12): 3336-46.
[http://dx.doi.org/10.1161/STROKEAHA.117.018505] [PMID: 29114096]
[48]
Franco R, Fernández-Suárez D. Alternatively activated microglia and macrophages in the central nervous system. Prog Neurobiol 2015; 131: 65-86.
[http://dx.doi.org/10.1016/j.pneurobio.2015.05.003] [PMID: 26067058]
[49]
Donnan GA, Fisher M, Macleod M, Davis SM. Stroke. Lancet 2008; 371(9624): 1612-23.
[http://dx.doi.org/10.1016/S0140-6736(08)60694-7] [PMID: 18468545]
[50]
Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell 2012; 148(6): 1204-22.
[http://dx.doi.org/10.1016/j.cell.2012.02.040] [PMID: 22424230]
[51]
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. Behav Brain Res 2015; 293: 189-97.
[http://dx.doi.org/10.1016/j.bbr.2015.07.043] [PMID: 26210934]
[52]
Sulica L. The superior laryngeal nerve: Function and dysfunction. Otolaryngol Clin North Am 2004; 37(1): 183-201.
[http://dx.doi.org/10.1016/S0030-6665(03)00175-0] [PMID: 15062693]
[53]
van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 2018; 19(4): 213-28.
[http://dx.doi.org/10.1038/nrm.2017.125] [PMID: 29339798]
[54]
Kao CY, Papoutsakis ET. Extracellular vesicles: Exosomes, microparticles, their parts, and their targets to enable their biomanufacturing and clinical applications. Curr Opin Biotechnol 2019; 60: 89-98.
[http://dx.doi.org/10.1016/j.copbio.2019.01.005] [PMID: 30851486]
[55]
Phinney DG, Pittenger MF. Concise review: MSC-derived exosomes for cell-free therapy. Stem Cells 2017; 35(4): 851-8.
[http://dx.doi.org/10.1002/stem.2575] [PMID: 28294454]
[56]
Stanko P, Altanerova U, Jakubechova J, Repiska V, Altaner C. Dental mesenchymal stem/stromal cells and their exosomes. Stem Cells Int 2018; 2018: 8973613.
[http://dx.doi.org/10.1155/2018/8973613] [PMID: 29760738]
[57]
Jarmalavičiūtė A, Tunaitis V, Pivoraitė U, Venalis A, Pivoriūnas A. Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine-induced apoptosis. Cytotherapy 2015; 17(7): 932-9.
[http://dx.doi.org/10.1016/j.jcyt.2014.07.013] [PMID: 25981557]
[58]
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. Stem Cells Transl Med 2019; 8(5): 490-9.
[http://dx.doi.org/10.1002/sctm.18-0162] [PMID: 30706999]
[59]
Li Y, Yang YY, Ren JL, Xu F, Chen FM, Li A. Exosomes secreted by stem cells from human exfoliated deciduous teeth contribute to functional recovery after traumatic brain injury by shifting microglia M1/M2 polarization in rats. Stem Cell Res Ther 2017; 8(1): 198.
[http://dx.doi.org/10.1186/s13287-017-0648-5] [PMID: 28962585]
[60]
Jonavičė U, Tunaitis V, Kriaučiūnaitė K, Jarmalavičiūtė A, Pivoriūnas A. Extracellular vesicles can act as a potent immunomodulators of human microglial cells. J Tissue Eng Regen Med 2019; 13(2): 309-18.
[http://dx.doi.org/10.1002/term.2810] [PMID: 30650469]
[61]
Sedgley CM, Botero TM. Dental stem cells and their sources. Dent Clin North Am 2012; 56(3): 549-61.
[http://dx.doi.org/10.1016/j.cden.2012.05.004] [PMID: 22835537]
[62]
Didilescu AC, Rusu MC, Nini G. Dental pulp as a stem cell reservoir. Rom J Morphol Embryol 2013; 54(3): 473-8.
[PMID: 24068393]
[63]
Zhao H, Chai Y. Stem cells in teeth and craniofacial bones. J Dent Res 2015; 94(11): 1495-501.
[http://dx.doi.org/10.1177/0022034515603972] [PMID: 26350960]
[64]
Abdullah MF, Abdullah SF, Omar NS, et al. Proliferation rate of stem cells derived from human dental pulp and identification of differentially expressed genes. Cell Biol Int 2014; 38(5): 582-90.
[http://dx.doi.org/10.1002/cbin.10229] [PMID: 24375868]
[65]
Zheng Z, Li C, Ha P, et al. CDKN2B upregulation prevents teratoma formation in multipotent fibromodulin-reprogrammed cells. J Clin Invest 2019; 129(8): 3236-51.
[http://dx.doi.org/10.1172/JCI125015] [PMID: 31305260]
[66]
Tan HL, Tan BZ, Goh WXT, Cua S, Choo A. In vivo surveillance and elimination of teratoma-forming human embryonic stem cells with monoclonal antibody 2448 targeting annexin A2. Biotechnol Bioeng 2019; 116(11): 2996-3005.
[http://dx.doi.org/10.1002/bit.27135] [PMID: 31388993]
[67]
Yoshihara M, Hayashizaki Y, Murakawa Y. Genomic instability of iPSCs: Challenges towards their clinical applications. Stem Cell Rev Rep 2017; 13(1): 7-16.
[http://dx.doi.org/10.1007/s12015-016-9680-6] [PMID: 27592701]
[68]
Kallunki T, Barisic M, Jäättelä M, Liu B. How to choose the right inducible gene expression system for mammalian studies? Cells 2019; 8(8): 796-812.
[http://dx.doi.org/10.3390/cells8080796] [PMID: 31366153]
[69]
Chen T, Li J, Jia Y, et al. Single-cell sequencing in the field of stem cells. Curr Genomics 2020; 21(8): 576-84.
[http://dx.doi.org/10.2174/1389202921999200624154445] [PMID: 33414679]
[70]
Zhang YT, He KJ, Zhang JB, Ma QH, Wang F, Liu CF. Advances in intranasal application of stem cells in the treatment of central nervous system diseases. Stem Cell Res Ther 2021; 12(1): 210-20.
[http://dx.doi.org/10.1186/s13287-021-02274-0] [PMID: 33762014]

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