Dental pulp stem cells and pulp regeneration

doi:10.3877/cma.j.issn.1674-1366.2022.06.001

Abstract

Abstract:

An intact and healthy dental pulp is crucial to maintain the integrity of tooth. A variety of impairments such as infection and trauma cause irreversible pulp damage, which require removal of pulp tissue and conventional root canal filing. However, this type of treatment fails to restore vital pulp. It is still a clinical challenge that how to regenerate pulp and prolong the lifespan of tooth. Dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHED) are isolated from the dental pulp of permanent teeth and exfoliated deciduous teeth, respectively. They are more suitable and practical kinds of seed cell sources for dental pulp regeneration due to their superior proliferation capacity, excellent neurogenic / angiogenic differentiation capability, and dental tissue origin. A few preclinical and clinical studies showed that implantation of autologous DPSCs or SHED can re-establish physiological pulp tissue structures. This review article sought to introduce the innate characteristics of DPSCs / SHED and the current state of dental pulp regeneration research.

Key words: Dental pulp stem cells, Stem cells from human exfoliated deciduous teeth, Dental pulp regeneration

Xueli Mao, Songtao Shi. Dental pulp stem cells and pulp regeneration[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2022, 16(06): 333-342.

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[1]	Goldberg M，Njeh A，Uzunoglu E. Is pulp inflammation a prerequisite for pulp healing and regeneration？[J]. Mediators Inflamm，2015:347649. DOI：10.1155/2015/347649.
[2]	Bjørndal L，Simon S，Tomson PL，et al. Management of deep caries and the exposed pulp[J]. Int Endod J，2019，52(7):949-973. DOI：10.1111/iej.13128.
[3]	Yang J，Yuan G，Chen Z. Pulp regeneration：Current approaches and future challenges[J]. Front Physiol，2016，7:58. DOI：10.3389/fphys.2016.00058.
[4]	Yahyazadehfar M，Ivancik J，Majd H，et al. On the mechanics of fatigue and fracture in teeth[J]. Appl Mech Rev，2014，66(3):0308031-3080319. DOI：10.1115/1.4027431.
[5]	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. DOI：10.1073/pnas.240309797.
[6]	Miura M，Gronthos S，Zhao M，et al. SHED：stem cells from human exfoliated deciduous teeth[J]. Proc Natl Acad Sci U S A，2003，100(10):5807-5812. DOI：10.1073/pnas.0937635100.
[7]	Gronthos S，Brahim J，Li W，et al. Stem cell properties of human dental pulp stem cells[J]. J Dent Res，2002，81(8):531-535. DOI：10.1177/154405910208100806.
[8]	Chang J，Zhang C，Tani-Ishii N，et al. NF-kappaB activation in human dental pulp stem cells by TNF and LPS[J]. J Dent Res，2005，84(11):994-998. DOI：10.1177/154405910508401105.
[9]	Scheller EL，Chang J，Wang CY. Wnt/beta-catenin inhibits dental pulp stem cell differentiation[J]. J Dent Res，2008，87(2):126-130. DOI：10.1177/154405910808700206.
[10]	Botero TM，Son JS，Vodopyanov D，et al. MAPK signaling is required for LPS-induced VEGF in pulp stem cells[J]. J Dent Res，2010，89(3):264-269. DOI：10.1177/0022034509357556.
[11]	Paino F，La Noce M，Tirino V，et al. Histone deacetylase inhibition with valproic acid downregulates osteocalcin gene expression in human dental pulp stem cells and osteoblasts：evidence for HDAC2 involvement[J]. Stem Cells，2014，32(1):279-289. DOI：10.1002/stem.1544.
[12]	Tan X，Dai Q. Characterization of microRNAs expression profiles in human dental-derived pluripotent stem cells[J]. PLoS One，2017，12(5):e0177832. DOI：10.1371/journal.pone.0177832.
[13]	Shen WC，Lai YC，Li LH，et al. Methylation and PTEN activation in dental pulp mesenchymal stem cells promotes osteogenesis and reduces oncogenesis[J]. Nat Commun，2019，10(1):2226. DOI：10.1038/s41467-019-10197-x.
[14]	Rosa V，Zhang Z，Grande RH，et al. Dental pulp tissue engineering in full-length human root canals[J]. J Dent Res，2013，92(11):970-975. DOI：10.1177/0022034513505772.
[15]	Song JS，Takimoto K，Jeon M，et al. Decellularized human dental pulp as a scaffold for regenerative endodontics[J]. J Dent Res，2017，96(6):640-646. DOI：10.1177/0022034517693606.
[16]	Alqahtani Q，Zaky SH，Patil A，et al. Decellularized swine dental pulp tissue for regenerative root canal therapy[J]. J Dent Res，2018，97(13):1460-1467. DOI：10.1177/0022034518785124.
[17]	Huang GT，Yamaza T，Shea LD，et al. Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model[J]. Tissue Eng Part A，2010，16(2):605-615. DOI：10.1089/ten.TEA.2009.0518.
[18]	Iohara K，Zheng L，Ito M，et al. Regeneration of dental pulp after pulpotomy by transplantation of CD31（-）/CD146（-）side population cells from a canine tooth[J]. Regen Med，2009，4(3):377-385. DOI：10.2217/rme.09.5.
[19]	Kuang R，Zhang Z，Jin X，et al. Nanofibrous spongy microspheres for the delivery of hypoxia-primed human dental pulp stem cells to regenerate vascularized dental pulp[J]. Acta Biomater，2016，33:225-234. DOI：10.1016/j.actbio.2016.01.032.
[20]	Murakami M，Horibe H，Iohara K，et al. The use of granulocyte-colony stimulating factor induced mobilization for isolation of dental pulp stem cells with high regenerative potential[J]. Biomaterials，2013，34(36):9036-9047. DOI：10.1016/j.biomaterials.2013.08.011.
[21]	Iohara K，Murakami M，Takeuchi N，et al. A novel combinatorial therapy with pulp stem cells and granulocyte colony-stimulating factor for total pulp regeneration[J]. Stem Cells Transl Med，2013，2(7):521-533. DOI：10.5966/sctm.2012-0132.
[22]	Iohara K，Nakashima M，Ito M，et al. Dentin regeneration by dental pulp stem cell therapy with recombinant human bone morphogenetic protein 2[J]. J Dent Res，2004，83(8):590-595. DOI：10.1177/154405910408300802.
[23]	Itoh Y，Sasaki JI，Hashimoto M，et al. Pulp regeneration by 3-dimensional dental pulp stem cell constructs[J]. J Dent Res，2018，97(10):1137-1143. DOI：10.1177/0022034518772260.
[24]	Iohara K，Imabayashi K，Ishizaka R，et al. Complete pulp regeneration after pulpectomy by transplantation of CD105⁺ stem cells with stromal cell-derived factor-1[J]. Tissue Eng Part A，2011，17(15/16):1911-1920. DOI：10.1089/ten.TEA.2010.0615.
[25]	Nakashima M，Iohara K，Murakami M，et al. Pulp regeneration by transplantation of dental pulp stem cells in pulpitis：A pilot clinical study[J]. Stem Cell Res Ther，2017，8(1):61. DOI：10.1186/s13287-017-0506-5.
[26]	Xuan K，Li B，Guo H，et al. Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth[J]. Sci Transl Med，2018，10(455):eaaf3227. DOI：10.1126/scitranslmed.aaf3227.
[27]	Takeda T，Tezuka Y，Horiuchi M，et al. Characterization of dental pulp stem cells of human tooth germs[J]. J Dent Res，2008，87(7):676-681. DOI：10.1177/154405910808700716.
[28]	Pisal RV，Suchanek J，Siller R，et al. Directed reprogramming of comprehensively characterized dental pulp stem cells extracted from natal tooth[J]. Sci Rep，2018，8(1):6168. DOI：10.1038/s41598-018-24421-z.
[29]	Kunimatsu R，Nakajima K，Awada T，et al. Comparative characterization of stem cells from human exfoliated deciduous teeth，dental pulp，and bone marrow-derived mesenchymal stem cells[J]. Biochem Biophys Res Commun，2018，501(1):193-198. DOI：10.1016/j.bbrc.2018.04.213.
[30]	Seo BM，Miura M，Gronthos S，et al. Investigation of multipotent postnatal stem cells from human periodontal ligament[J]. Lancet，2004，364(9429):149-155. DOI：10.1016/S0140-6736(04)16627-0.
[31]	Sonoyama W，Liu Y，Yamaza T，et al. Characterization of the apical papilla and its residing stem cells from human immature permanent teeth：A pilot study[J]. J Endod，2008，34(2):166-171. DOI：10.1016/j.joen.2007.11.021.
[32]	Zhang Q，Shi S，Liu Y，et al. Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis[J]. J Immunol，2009，183(12):7787-7798. DOI：10.4049/jimmunol.0902318.
[33]	Morsczeck C，Götz W，Schierholz J，et al. Isolation of precursor cells（PCs）from human dental follicle of wisdom teeth[J]. Matrix Biol，2005，24(2):155-165. DOI：10.1016/j.matbio.2004.12.004.
[34]	Botelho J，Cavacas MA，Machado V，et al. Dental stem cells：Recent progresses in tissue engineering and regenerative medicine[J]. Ann Med，2017，49(8):644-651. DOI：10.1080/07853890.2017.1347705.
[35]	An Z，Sabalic M，Bloomquist RF，et al. A quiescent cell population replenishes mesenchymal stem cells to drive accelerated growth in mouse incisors[J]. Nat Commun，2018，9(1):378. DOI：10.1038/s41467-017-02785-6.
[36]	Karaöz E，Doğan BN，Aksoy A，et al. Isolation and in vitro characterisation of dental pulp stem cells from natal teeth[J]. Histochem Cell Biol，2010，133(1):95-112. DOI：10.1007/s00418-009-0646-5.
[37]	Zhao H，Feng J，Seidel K，et al. Secretion of shh by a neurovascular bundle niche supports mesenchymal stem cell homeostasis in the adult mouse incisor[J]. Cell Stem Cell，2014，14(2):160-173. DOI：10.1016/j.stem.2013.12.013.
[38]	Vidovic I，Banerjee A，Fatahi R，et al. αSMA-expressing perivascular cells represent dental pulp progenitors in vivo[J]. J Dent Res，2017，96(3):323-330. DOI：10.1177/0022034516678208.
[39]	Shi S，Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp[J]. J Bone Miner Res，2003，18(4):696-704. DOI：10.1359/jbmr.2003.18.4.696.
[40]	Liu Y，Jing H，Kou X，et al. PD-1 is required to maintain stem cell properties in human dental pulp stem cells[J]. Cell Death Differ，2018，25(7):1350-1360. DOI：10.1038/s41418-018-0077-8.
[41]	Ishizaka R，Hayashi Y，Iohara K，et al. Stimulation of angiogenesis，neurogenesis and regeneration by side population cells from dental pulp[J]. Biomaterials，2013，34(8):1888-1897. DOI：10.1016/j.biomaterials.2012.10.045.
[42]	Ma L，Huang Z，Wu D，et al. CD146 controls the quality of clinical grade mesenchymal stem cells from human dental pulp[J]. Stem Cell Res Ther，2021，12(1):488. DOI：10.1186/s13287-021-02559-4.
[43]	Fageeh HN，Bhandi S，Mashyakhy M，et al. Viability of quercetin-induced dental pulp stem cells in forming living cellular constructs for soft tissue augmentation[J]. J Pers Med，2021，11(5):430. DOI：10.3390/jpm11050430.
[44]	Hu L，Zhao B，Gao Z，et al. Regeneration characteristics of different dental derived stem cell sheets[J]. J Oral Rehabil，2020，47 Suppl 1:66-72. DOI：10.1111/joor.12839.
[45]	Ito Y，Yeo JY，Chytil A，et al. Conditional inactivation of Tgfbr2 in cranial neural crest causes cleft palate and calvaria defects[J]. Development，2003，130(21):5269-5280. DOI：10.1242/dev.00708.
[46]	Achilleos A，Trainor PA. Neural crest stem cells：Discovery，properties and potential for therapy[J]. Cell Res，2012，22(2):288-304. DOI：10.1038/cr.2012.11.
[47]	Kaukua N，Shahidi MK，Konstantinidou C，et al. Glial origin of mesenchymal stem cells in a tooth model system[J]. Nature，2014，513(7519):551-554. DOI：10.1038/nature13536.
[48]	Govindasamy V，Abdullah AN，Ronald VS，et al. Inherent differential propensity of dental pulp stem cells derived from human deciduous and permanent teeth[J]. J Endod，2010，36(9):1504-1515. DOI：10.1016/j.joen.2010.05.006.
[49]	Martínez-Sarrà E，Montori S，Gil-Recio C，et al. Human dental pulp pluripotent-like stem cells promote wound healing and muscle regeneration[J]. Stem Cell Res Ther，2017，8(1):175. DOI：10.1186/s13287-017-0621-3.
[50]	Arthur A，Rychkov G，Shi S，et al. Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues[J]. Stem Cells，2008，26(7):1787-1795. DOI：10.1634/stemcells.2007-0979.
[51]	Crisan M，Yap S，Casteilla L，et al. A perivascular origin for mesenchymal stem cells in multiple human organs[J]. Cell Stem Cell，2008，3(3):301-313. DOI：10.1016/j.stem.2008.07.003.
[52]	Yang JW，Zhang YF，Wan CY，et al. Autophagy in SDF-1α-mediated DPSC migration and pulp regeneration[J]. Biomaterials，2015，44:11-23. DOI：10.1016/j.biomaterials.2014.12.006.
[53]	Zhang Z，Nor F，Oh M，et al. Wnt/β-catenin signaling determines the vasculogenic fate of postnatal mesenchymal stem cells[J]. Stem Cells，2016，34(6):1576-1587. DOI：10.1002/stem.2334.
[54]	Zhao H，Feng J，Seidel K，et al. Secretion of shh by a neurovascular bundle niche supports mesenchymal stem cell homeostasis in the adult mouse incisor[J]. Cell Stem Cell，2018，23(1):147. DOI：10.1016/j.stem.2018.05.023.
[55]	Sui BD，Hu CH，Zheng CX，et al. Microenvironmental views on mesenchymal stem cell differentiation in aging[J]. J Dent Res，2016，95(12):1333-1340. DOI：10.1177/0022034516653589.
[56]	Cordeiro MM，Dong Z，Kaneko T，et al. Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth[J]. J Endod，2008，34(8):962-969. DOI：10.1016/j.joen.2008.04.009.
[57]	Sui B，Wu D，Xiang L，et al. Dental pulp stem cells：From discovery to clinical application[J]. J Endod，2020，46(9S):S46-S55. DOI：10.1016/j.joen.2020.06.027.
[58]	Schmalz G，Widbiller M，Galler KM. Clinical perspectives of pulp regeneration[J]. J Endod，2020，46(9S):S161-S174. DOI：10.1016/j.joen.2020.06.037.
[59]	Sui B，Chen C，Kou X，et al. Pulp stem cell-mediated functional pulp regeneration[J]. J Dent Res，2019，98(1):27-35. DOI：10.1177/0022034518808754.
[60]	Zheng L，Yang F，Shen H，et al. The effect of composition of calcium phosphate composite scaffolds on the formation of tooth tissue from human dental pulp stem cells[J]. Biomaterials，2011，32(29):7053-7059. DOI：10.1016/j.biomaterials.2011.06.004.
[61]	Wang J，Ma H，Jin X，et al. The effect of scaffold architecture on odontogenic differentiation of human dental pulp stem cells[J]. Biomaterials，2011，32(31):7822-7830. DOI：10.1016/j.biomaterials.2011.04.034.
[62]	Mu X，Shi L，Pan S，et al. A customized self-assembling peptide hydrogel-wrapped stem cell factor targeting pulp regeneration rich in vascular-like structures[J]. ACS Omega，2020，5(27):16568-16574. DOI：10.1021/acsomega.0c01266.
[63]	Ducret M，Montembault A，Josse J，et al. Design and characterization of a chitosan-enriched fibrin hydrogel for human dental pulp regeneration[J]. Dent Mater，2019，35(4):523-533. DOI：10.1016/j.dental.2019.01.018.
[64]	Lu Q，Pandya M，Rufaihah AJ，et al. Modulation of dental pulp stem cell odontogenesis in a tunable PEG-fibrinogen hydrogel system[J]. Stem Cells Int，2015:525367. DOI：10.1155/2015/525367.
[65]	Dissanayaka WL，Hargreaves KM，Jin L，et al. The interplay of dental pulp stem cells and endothelial cells in an injectable peptide hydrogel on angiogenesis and pulp regeneration in vivo[J]. Tissue Eng Part A，2015，21(3/4):550-563. DOI：10.1089/ten.TEA.2014.0154.
[66]	Xia K，Chen Z，Chen J，et al. RGD- and VEGF-mimetic peptide epitope-functionalized self-assembling peptide hydrogels promote dentin-pulp complex regeneration[J]. Int J Nanomedicine，2020，15:6631-6647. DOI：10.2147/IJN.S253576.
[67]	Zhang W，Zheng Y，Liu H，et al. A non-invasive monitoring of USPIO labeled silk fibroin/hydroxyapatite scaffold loaded DPSCs for dental pulp regeneration[J]. Mater Sci Eng C Mater Biol Appl，2019，103:109736. DOI：10.1016/j.msec.2019.05.021.
[68]	Hilkens P，Bronckaers A，Ratajczak J，et al. The angiogenic potential of DPSCs and SCAPs in an in vivo model of dental pulp regeneration[J]. Stem Cells Int，2017:2582080. DOI：10.1155/2017/2582080.
[69]	Zhang L，Yu Y，Joubert C，et al. Differentiation of dental pulp stem cells on gutta-percha scaffolds[J]. Polymers（Basel），2016，8(5):193. DOI：10.3390/polym8050193.
[70]	Li X，Ma C，Xie X，et al. Pulp regeneration in a full-length human tooth root using a hierarchical nanofibrous microsphere system[J]. Acta Biomater，2016，35:57-67. DOI：10.1016/j.actbio.2016.02.040.
[71]	Wang Y，Zhao Y，Jia W，et al. Preliminary study on dental pulp stem cell-mediated pulp regeneration in canine immature permanent teeth[J]. J Endod，2013，39(2):195-201. DOI：10.1016/j.joen.2012.10.002.
[72]	Solaroglu I，Cahill J，Jadhav V，et al. A novel neuroprotectant granulocyte-colony stimulating factor[J]. Stroke，2006，37(4):1123-1128. DOI：10.1161/01.STR.0000208205.26253.96.
[73]	Nakayama H，Iohara K，Hayashi Y，et al. Enhanced regeneration potential of mobilized dental pulp stem cells from immature teeth[J]. Oral Dis，2017，23(5):620-628. DOI：10.1111/odi.12619.
[74]	Chen J，Xu H，Xia K，et al. Resolvin E1 accelerates pulp repair by regulating inflammation and stimulating dentin regeneration in dental pulp stem cells[J]. Stem Cell Res Ther，2021，12(1):75. DOI：10.1186/s13287-021-02141-y.
[75]	Li J，Diao S，Yang H，et al. IGFBP5 promotes angiogenic and neurogenic differentiation potential of dental pulp stem cells[J]. Dev Growth Differ，2019，61(9):457-465. DOI：10.1111/dgd.12632.
[76]	Sonoda S，Yamaza H，Ma L，et al. Interferon-gamma improves impaired dentinogenic and immunosuppressive functions of irreversible pulpitis-derived human dental pulp stem cells[J]. Sci Rep，2016，6:19286. DOI：10.1038/srep19286.
[77]	Strojny C，Boyle M，Bartholomew A，et al. Interferon gamma-treated dental pulp stem cells promote human mesenchymal stem cell migration in vitro[J]. J Endod，2015，41(8):1259-1264. DOI：10.1016/j.joen.2015.02.018.
[78]	Rufas P，Jeanneau C，Rombouts C，et al. Complement C3a mobilizes dental pulp stem cells and specifically guides pulp fibroblast recruitment[J]. J Endod，2016，42(9):1377-1384. DOI：10.1016/j.joen.2016.06.011.
[79]	Kim JY，Xin X，Moioli EK，et al. Regeneration of dental-pulp-like tissue by chemotaxis-induced cell homing[J]. Tissue Eng Part A，2010，16(10):3023-3031. DOI：10.1089/ten.TEA.2010.0181.
[80]	Eramo S，Natali A，Pinna R，et al. Dental pulp regeneration via cell homing[J]. Int Endod J，2018，51(4):405-419. DOI：10.z1111/iej.12868.
[81]	Kim SG，Zheng Y，Zhou J，et al. Dentin and dental pulp regeneration by the patient′s endogenous cells[J]. Endod Topics，2013，28(1):106-117. DOI：10.1111/etp.12037.
[82]	Dissanayaka WL，Zhu L，Hargreaves KM，et al. Scaffold-free prevascularized microtissue spheroids for pulp regeneration[J]. J Dent Res，2014，93(12):1296-1303. DOI：10.1177/0022034514550040.
[83]	Guo H，Zhao W，Liu A，et al. SHED promote angiogenesis in stem cell-mediated dental pulp regeneration[J]. Biochem Biophys Res Commun，2020，529(4):1158-1164. DOI：10.1016/j.bbrc.2020.06.151.
[84]	Sonoyama W，Liu Y，Fang D，et al. Mesenchymal stem cell-mediated functional tooth regeneration in swine[J]. PLoS One，2006，1(1):e79. DOI：10.1371/journal.pone.0000079.
[85]	Zhu X，Liu J，Yu Z，et al. A miniature swine model for stem cell-based de novo regeneration of dental pulp and dentin-like tissue[J]. Tissue Eng Part C Methods，2018，24(2):108-120. DOI：10.1089/ten.tec.2017.0342.
[86]	Wei F，Song T，Ding G，et al. Functional tooth restoration by allogeneic mesenchymal stem cell-based bio-root regeneration in swine[J]. Stem Cells Dev，2013，22(12):1752-1762. DOI：10.1089/scd.2012.0688.
[87]	Wang X，Thibodeau B，Trope M，et al. Histologic characterization of regenerated tissues in canal space after the revitalization/revascularization procedure of immature dog teeth with apical periodontitis[J]. J Endod，2010，36(1):56-63. DOI：10.1016/j.joen.2009.09.039.
[88]	Liu Y，Chen C，Liu S，et al. Acetylsalicylic acid treatment improves differentiation and immunomodulation of SHED[J]. J Dent Res，2015，94(1):209-218. DOI：10.1177/0022034514557672.
[89]	Hattori Y，Kim H，Tsuboi N，et al. Therapeutic potential of stem cells from human exfoliated deciduous teeth in models of acute kidney injury[J]. PLoS One，2015，10(10):e0140121. DOI：10.1371/journal.pone.0140121.
[90]	Yamaza T，Kentaro A，Chen C，et al. Immunomodulatory properties of stem cells from human exfoliated deciduous teeth[J]. Stem Cell Res Ther，2010，1(1):5. DOI：10.1186/scrt5.
[91]	Liu Y，Wang L，Kikuiri T，et al. Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α[J]. Nat Med，2011，17(12):1594-1601. DOI：10.1038/nm.2542.
[92]	Chen FM，Gao LN，Tian BM，et al. Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells：A randomized clinical trial[J]. Stem Cell Res Ther，2016，7:33. DOI：10.1186/s13287-016-0288-1.
[93]	Inoue T，Sugiyama M，Hattori H，et al. Stem cells from human exfoliated deciduous tooth-derived conditioned medium enhance recovery of focal cerebral ischemia in rats[J]. Tissue Eng Part A，2013，19(1-2):24-29. DOI：10.1089/ten.TEA.2011.0385.
[94]	Fujii H，Matsubara K，Sakai K，et al. Dopaminergic differentiation of stem cells from human deciduous teeth and their therapeutic benefits for Parkinsonian rats[J]. Brain Res，2015，1613:59-72. DOI：10.1016/j.brainres.2015.04.001.
[95]	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. DOI：10.1016/j.brainres.2017.03.015.
[96]	Yang C，Li X，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. DOI：10.1088/1741-2552/aa596b.
[97]	Zhao L，Li Y，Kou X，et al. Stem cells from human exfoliated deciduous teeth ameliorate autistic-like behaviors of SHANK3 mutant beagle dogs[J]. Stem Cells Transl Med，2022，11(7):778-789. DOI：10.1093/stcltm/szac028.
[98]	Zheng Y，Liu Y，Zhang CM，et al. Stem cells from deciduous tooth repair mandibular defect in swine[J]. J Dent Res，2009，88(3):249-254. DOI：10.1177/0022034509333804.
[99]	Shi X，Mao J，Liu Y. Pulp stem cells derived from human permanent and deciduous teeth：Biological characteristics and therapeutic applications[J]. Stem Cells Transl Med，2020，9(4):445-464. DOI：10.1002/sctm.19-0398.
[100]	Ma L，Makino Y，Yamaza H，et al. Cryopreserved dental pulp tissues of exfoliated deciduous teeth is a feasible stem cell resource for regenerative medicine[J]. PLoS One，2012，7(12):e51777. DOI：10.1371/journal.pone.0051777.
[101]	Ueda M，Nishino Y. Cell-based cytokine therapy for skin rejuvenation[J]. J Craniofac Surg，2010，21(6):1861-1866. DOI：10.1097/SCS.0b013e3181f43f0a.
[102]	Sui BD，Zhu B，Hu CH，et al. Reconstruction of regenerative stem cell niche by cell aggregate engineering[J]. Methods Mol Biol，2019，2002:87-99. DOI：10.1007/7651_2018_186.
[103]	Nakashima M，Fukuyama F，Iohara K. Pulp regenerative cell therapy for mature molars：A report of 2 cases[J]. J Endod，2022，48(10):1334-1340.e1. DOI：10.1016/j.joen.2022.07.010.
[104]	Manimaran K，Sankaranarayanan S，Ravi VR，et al. Treatment of osteoradionecrosis of mandible with bone marrow concentrate and with dental pulp stem cells[J]. Ann Maxillofac Surg，2014，4(2):189-192. DOI：10.4103/2231-0746.147130.
[105]	Li W，Jiao X，Song J，et al. Therapeutic potential of stem cells from human exfoliated deciduous teeth infusion into patients with type 2 diabetes depends on basal lipid levels and islet function[J]. Stem Cells Transl Med，2021，10(7):956-967. DOI：10.1002/sctm.20-0303.
[106]	Suda S，Nito C，Ihara M，et al. Randomised placebo-controlled multicentre trial to evaluate the efficacy and safety of JTR-161，allogeneic human dental pulp stem cells，in patients with Acute Ischaemic stRoke（J-REPAIR）[J]. BMJ Open，2022，12(5):e054269. DOI：10.1136/bmjopen-2021-054269.

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