مروری بر سلول‌های بنیادی پالپ دندان: جداسازی، شناسایی وکاربرد در پزشکی بازساختی

نوع مقاله : مقاله مروری

نویسندگان

1 -علوم تشریح و بیولوژی سلولی،دانشکده پزشکی، دانشگاه علوم پزشکی مشهد، مشهد، ایران -کمیته تحقیقات دانشجویی، دانشکده پزشکی، دانشگاه

2 گروه علوم تشریح و بیولوژی سلولی، دانشکده پزشکی، دانشگاه علوم پزشکی مشهد، مشهد، ایران.

3 دانشجوی دنداپزشکی،کمیته تحقیقات دانشجویی، دانشکده دندان پزشکی، دانشگاه علوم پزشکی مشهد، مشهد، ایران.

4 علوم تشریح و بیولوژی تولید مثل، دانشکده پزشکی، دانشگاه علوم پزشکی مشهد، مشهد،ایران

چکیده

مقدمه و هدف: سلول‌های بنیادی که دارای ظرفیت خود نوسازی و تمایز چند سلولی هستند، نوید راهبردهای درمانی جدیدی را برای غلبه بر موانع در پتانسیل بازسازی می‌دهند. سهولت جداسازی سلول‌های بنیادی پالپ دندان (DPSCs) از دندان‌های دور ریخته شده یا برداشته‌شده، منبع امیدوارکننده‌ای جهت پیوند سلول‌های اتولوگ می‌باشد. مطالعه مروری پیش رو، به طور خلاصه مشخصات DPSCs را برجسته کرده و سپس بر روی کاربردهای DPSCs در وسعت پزشکی بازساختی تمرکز می‌کند.
مواد و روش‏ها: پژوهش حاضر یک مطالعه مروری بود که با بکارگیری کلیدواژه های dental pulp، regenerative medicine، mesenchymal stem cells، tissue regenerationدر پایگاه های Web of Science ،PubMed ،Google Scholar، SID، Magiran بدون محدودیت زمانی مقالات استخراج شدند. معیارهای ورود شامل مطالعاتی بودند که همراستا با هدف تحقیق بودند.
یافته‏ها: DPSCs که از دودمان تاج عصبی جمجمه‌ای مشتق می شوند پتانسیل قابل توجهی در تمایز عصبی دارند. بعلاوه این سلول ها مارکرهای متعددی را بیان می‌کنند که برای بازسازی مفید هستند. DPSCs همچنین می‌توانند فاکتورهای تعدیل‌کننده ایمنی را بیان کنند که تشکیل رگ‌های خونی را تحریک کرده و بازسازی و ترمیم بافت آسیب دیده را افزایش می‌دهد. این خواص منحصر به فرد همراه با قابلیت دسترسی آماده آن‌ها، DPSCs را به یک منبع سلولی جذاب و کاربردی برای مهندسی بافت و استفاده در پزشکی بازساختی تبدیل کرده است.
نتیجه‏گیری: روی هم رفته، DPSCs منبع سلول‌های بنیادی ایده آلی برای رویکردهای درمانی ترمیم و بازسازی بافت در بیماری‌ها و آسیب‌ها هستند. با این حال نیاز به مطالعات بالینی بیشتر ضروری بنظر می‌رسد.

کلیدواژه‌ها


1.     Sylvester KG, Longaker MT. Stem cells: review and update. Archives of surgery. 2004;139(1):93-9.
2.     Kim N, Cho S-G. Clinical applications of mesenchymal stem cells. The Korean journal of internal medicine. 2013;28(4):387.
3.     Giebel B, Beckmann J. Asymmetric cell divisions of human hematopoietic stem and progenitor cells meet endosomes. Cell Cycle. 2007;6(18):2201-4.
4.     de Almeida M, de Almeida CV, Graner EM, Brondani GE, de Abreu-Tarazi MF. Pre-procambial cells are niches for pluripotent and totipotent stem-like cells for organogenesis and somatic embryogenesis in the peach palm: a histological study. Plant cell reports. 2012;31(8):1495-515.
5.     Hassani S-N, Moradi S, Taleahmad S, Braun T, Baharvand H. Transition of inner cell mass to embryonic stem cells: mechanisms, facts, and hypotheses. Cellular and Molecular Life Sciences. 2019;76(5):873-92.
6.     Gafni Y, Turgeman G, Liebergal M, Pelled G, Gazit Z, Gazit D. Stem cells as vehicles for orthopedic gene therapy. Gene Therapy. 2004;11(4):417-26.
7.     Shafieian R, Matin MM, Rahpeyma A, Fazel A, Sedigh HS, Sadr-Nabavi A, et al. The effect of platelet-rich plasma on human mesenchymal stem cell-induced bone regeneration of canine alveolar defects with calcium phosphate-based scaffolds. Iranian journal of basic medical sciences. 2017;20(10):1131-40.
8.     Andrzejewska A, Lukomska B, Janowski M. Concise review: mesenchymal stem cells: from roots to boost. Stem Cells. 2019;37(7):855-64.
9.     Ledesma-Martínez E, Mendoza-Núñez VM, Santiago-Osorio E. Mesenchymal stem cells derived from dental pulp: a review. Stem cells international. 2016;2016.
10.    Shafieian R, Moghadam Matin M, Rahpeyma A, Fazel A, Salari Sedigh H, Sadr-Nabavi A, et al. Effects of Human Adipose-derived Stem Cells and Platelet-rich Plasma on Healing Response of Canine Alveolar Surgical Bone Defects. The Archives of Bone and Joint Surgery. 2017;5(6):406-18.
11.    Maxson S, Lopez EA, Yoo D, Danilkovitch-Miagkova A, LeRoux MA. Concise review: role of mesenchymal stem cells in wound repair. Stem cells translational medicine. 2012;1(2):142-9.
12.    Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, et al. SHED: stem cells from human exfoliated deciduous teeth. Proceedings of the National Academy of Sciences. 2003;100(10):5807-12.
13.    Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proceedings of the National Academy of Sciences. 2000;97(25):13625-30.
14.    Babaki D, Matin MM. Odontoblast-like cytodifferentiation of dental stem cells: a review. Iranian Endodontic Journal. 2020;15(2):79-89.
15.    Wang R, Ji Q, Meng C, Liu H, Fan C, Lipkind S, et al. Role of gingival mesenchymal stem cell exosomes in macrophage polarization under inflammatory conditions. International immunopharmacology. 2020;81 10603.
16.    Wang D, Wang Y, Tian W, Pan J. Advances of tooth-derived stem cells in neural diseases treatments and nerve tissue regeneration. Cell Proliferation. 2019;52(3):e12572.
17.    Haratizadeh S, Bojnordi MN, Niapour A, Bakhtiari M, Hamidabadi HG. Improvement of neuroglial differentiation from human dental pulp stem cells using CSF. Journal of Mazandaran University of Medical Sciences. 2016;26(140):1-14.
18.    Junqueira LC, Mescher AL. Junqueira's basic histology: text & atlas/Anthony L. Mescher. New York [etc.]: McGraw-Hill Medical; 2013.
19.    Lei M, Li K, Li B, Gao LN, Chen FM, Jin Y. Mesenchymal stem cell characteristics of dental pulp and periodontal ligament stem cells after in vivo transplantation. Biomaterials. 2014;35(24):6332-43.
20.    Radunovic M, De Colli M, De Marco P, Di Nisio C, Fontana A, Piattelli A, et al. Graphene oxide enrichment of collagen membranes improves DPSCs differentiation and controls inflammation occurrence. Journal of Biomedical Materials Research Part A. 2017;105(8):2312-20.
21.    Uribe-Echevarria Zubizarreta V, Agliano A, Unda Rodríguez FJ, Ibarretxe Bilbao G. Wnt signaling reprograms metabolism in dental pulp stem cells. 2019.
22.    Ahmadi F, Dalirsani Z, Tayarani-Najaran Z, Ebrahimzadeh-Bideskan A, Shafieian R. A Comparative Analysis of Photobiomodulation-Mediated Biological Effects of Single Versus Double Irradiation on Dental Pulp Stem Cells: An In Vitro Study. Photobiomodulation, Photomedicine, and Laser Surgery. 2022;40(5):334-42.
23.    Kerkis I, Caplan AI. Stem cells in dental pulp of deciduous teeth. Tissue Engineering Part B: Reviews. 2012;18(2):129-38.
24.    Dave JR, Tomar GB. Dental Tissue− Derived Mesenchymal Stem Cells: Applications in Tissue Engineering. Critical Reviews™ in Biomedical Engineering. 2018;46
25.    Pierdomenico L, Bonsi L, Calvitti M, Rondelli D, Arpinati M, Chirumbolo G, et al. Multipotent mesenchymal stem cells with immunosuppressive activity can be easily isolated from dental pulp. Transplantation. 2005;80(6):836-42
26.    Perry BC, Zhou D, Wu X, Yang F-C, Byers MA, Chu T-MG, et al. Collection, cryopreservation, and characterization of human dental pulp–derived mesenchymal stem cells for banking and clinical use. Tissue Engineering Part C: Methods. 2008;14(2):149-56.
27.    Shariatnia F, Moallem SA, Ahmadimanesh M, Ramazani E, Tayarani-Najaran Z. Investigation of the appropriate isolation methods of human dental pulp stem cells from third molars for osteogenic and adipogenic differentiation. Iranian Journal of Physiology and Pharmacology. 2019;3(2):147-2.
28.    Hollands P, Aboyeji D, Orcharton M. Dental pulp stem cells in regenerative medicine. British dental journal. 2018;224(9):747-50.
29.    Rodas-Junco BA, Villicana C. Dental pulp stem cells: current advances in isolation, expansion and preservation. Tissue engineering and regenerative medicine. 2017;14(4):333-47.
30.    Spath L, Rotilio V, Alessandrini M, Gambara G, De Angelis L, Mancini M, et al. Explant‐derived human dental pulp stem cells enhance differentiation and proliferation potentials. Journal of Cellular and Molecular Medicine. 2010;14(6b):1635-44.
31.    Takeda-Kawaguchi T, Sugiyama K, Chikusa S, Iida K, Aoki H, Tamaoki N, et al. Derivation of iPSCs after culture of human dental pulp cells under defined conditions. PLoS One. 2014;9(12):e115392.
32.    Hilkens P, Gervois P, Fanton Y, Vanormelingen J, Martens W, Struys T, et al. Effect of isolation methodology on stem cell properties and multilineage differentiation potential of human dental pulp stem cells. Cell and tissue research. 2013;353(1):65-78.
33.    Huang GT-J, Sonoyama W, Chen J, Park SH. In vitro characterization of human dental pulp cells: various isolation methods and culturing environments. Cell and tissue research. 2006;324(2):225-36.
34.    Karamzadeh R, Eslaminejad MB, Aflatoonian R. Isolation, characterization and comparative differentiation of human dental pulp stem cells derived from permanent teeth by using two different methods. Journal of visualized experiments: JoVE. 2012
35.    Kleinman H, Luckenbill-Edds L, Cannon F, Sephel G. Use of extracellular matrix components for cell culture. Analytical biochemistry. 1987;166(1):1-13.
36.    Vancha AR, Govindaraju S, Parsa KV, Jasti M, González-García M, Ballestero RP. Use of polyethyleneimine polymer in cell culture as attachment factor and lipofection enhancer. BMC biotechnology. 2004;4(1):1-12.
37.    Saha K, Mei Y, Reisterer CM, Pyzocha NK, Yang J, Muffat J, et al. Surface-engineered substrates for improved human pluripotent stem cell culture under fully defined conditions. Proceedings of the National Academy of Sciences. 2011;108(46):18714-9.
38.    Kim S-H, Turnbull J, Guimond S. Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. The Journal of endocrinology. 2011;209(2):139-51.
39.    Chen XD, Dusevich V, Feng JQ, Manolagas SC, Jilka RL. Extracellular matrix made by bone marrow cells facilitates expansion of marrow‐derived mesenchymal progenitor cells and prevents their differentiation into osteoblasts. Journal of bone and mineral research. 2007;22(12):1943-56.
40.    Lizier NF, Kerkis A, Gomes CM, Hebling J, Oliveira CF, Caplan AI, et al. Scaling-up of dental pulp stem cells isolated from multiple niches. PLoS One. 2012;7(6):e39885.
41.    Zomorodian E, Baghaban Eslaminejad M. Mesenchymal stem cells as a potent cell source for bone regeneration. Stem cells international. 2012;2012.
42.    Hagar MN, Yazid F, Luchman NA, Ariffin SHZ, Wahab RMA. Comparative evaluation of osteogenic differentiation potential of stem cells derived from dental pulp and exfoliated deciduous teeth cultured over granular hydroxyapatite based scaffold. BMC Oral Health. 2021;21.
43.    Atari M, Gil-Recio C, Fabregat M, García-Fernández D, Barajas M, Carrasco MA, et al. Dental pulp of the third molar: a new source of pluripotent-like stem cells. Journal of cell science. 2012;125(14):3343-56.
44.    Akpinar G, Kasap M, Aksoy A, Duruksu G, Gacar G, Karaoz E. Phenotypic and proteomic characteristics of human dental pulp derived mesenchymal stem cells from a natal, an exfoliated deciduous, and an impacted third molar tooth. Stem Cells International. 2014;2014.
45.    Hoseini SM, Kalantar F, Kalantar SM, Bahrami AR, Zareien F, Moghadam matin M. Mesenchymal Stem Cells: Interactions with Immune Cells and Immunosuppressive-Immunomodulatory Properties. The Scientific Journal of Iranian Blood Transfusion Organization. 2020;17(2):147-69.
46.    Xue C, Xie J, Zhao D, Lin S, Zhou T, Shi S, et al. The JAK/STAT 3 signalling pathway regulated angiogenesis in an endothelial cell/adipose‐derived stromal cell co‐culture, 3D gel model. Cell proliferation. 2017;50(1):e12307.
47.    Asutay F, Acar HA, Yolcu U, Kırtay M, Alan H. Dental stem cell sources and their potentials for bone tissue engineering. Journal of Istanbul University Faculty of Dentistry. 2015;49(2):51.
48.    Goldberg M, Smith AJ. Cells and extracellular matrices of dentin and pulp: a biological basis for repair and tissue engineering. Critical Reviews in Oral Biology & Medicine. 2004;15(1):13-27.
49.    Kim S-H, Kim Y-S, Lee S-Y, Kim K-H, Lee Y-M, Kim W-K, et al. Gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow. Journal of periodontal & implant science. 2011;41(4):192-200.
50.    Kumar A, Kumar V, Rattan V, Jha V, Bhattacharyya S. Secretome cues modulate the neurogenic potential of bone marrow and dental stem cells. Molecular neurobiology. 2017;54(6):4672-82.
51.    Tamaki Y, Nakahara T, Ishikawa H, Sato S. In vitro analysis of mesenchymal stem cells derived from human teeth and bone marrow. Odontology. 2013;101(2):121-32.
52.    Yu J, Wang Y, Deng Z, Tang L, Li Y, Shi J, et al. Odontogenic capability: bone marrow stromal stem cells versus dental pulp stem cells. Biology of the Cell. 2007;99(8):465-74.
53.    Song M, Lee JH, Bae J, Bu Y, Kim EC. Human Dental Pulp Stem Cells Are More Effective Than Human Bone Marrow-Derived Mesenchymal Stem Cells in Cerebral Ischemic Injury. Cell Transplant. 2017;26(6):1001-16.
54.    Ji L, Bao L, Gu Z, Zhou Q, Liang Y, Zheng Y, et al. Comparison of immunomodulatory properties of exosomes derived from bone marrow mesenchymal stem cells and dental pulp stem cells. Immunologic research. 2019;67(4):432-42.
55.    Komarova S, Roth J, Alvarez R, Curiel DT, Pereboeva L. Targeting of mesenchymal stem cells to ovarian tumors via an artificial receptor. Journal of ovarian research. 2010;3(1):1-14.
56.    Laino G, d'Aquino R, Graziano A, Lanza V, Carinci F, Naro F, et al. A new population of human adult dental pulp stem cells: a useful source of living autologous fibrous bone tissue (LAB). Journal of bone and mineral research. 2005;20(8):1394-402.
57.    Makridakis M, Roubelakis MG, Vlahou A. Stem cells: insights into the secretome. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics. 2013;1834(11):2380-4.
58.    Lin H, Chen H, Zhao X, Chen Z, Zhang P, Tian Y, et al. Advances in mesenchymal stem cell conditioned medium-mediated periodontal tissue regeneration. Journal of Translational Medicine. 2021;19(1):1-13.
59.    Skalnikova HK. Proteomic techniques for characterisation of mesenchymal stem cell secretome. Biochimie. 2013;95(12):2196-211.
60.    Ogata K, Matsumura-Kawashima M, Moriyama M, Kawado T, Nakamura S. Dental pulp-derived stem cell-conditioned media attenuates secondary Sjögren's syndrome via suppression of inflammatory cytokines in the submandibular glands. Regenerative therapy. 2021;16:73-80.
61.    Perera JR, Gikas PD, Bentley G. The present state of treatments for articular cartilage defects in the knee. Ann R Coll Surg Engl. 2012;94(6):381-7.
62.    Showery JE, Kusnezov NA, Dunn JC, Bader JO, Belmont Jr PJ, Waterman BR. The rising incidence of degenerative and posttraumatic osteoarthritis of the knee in the United States military. The Journal of arthroplasty. 2016;31(10):2108-14.
63.    Kubosch EJ, Lang G, Furst D, Kubosch D, Izadpanah K, Rolauffs B, et al. The potential for synovium-derived stem cells in cartilage repair. Current stem cell research & therapy. 2018;13(3):174-84.
64.    Zainal Ariffin SH, Kermani S, Megat Abdul Wahab R, Senafi S, Zainal Ariffin Z, Abdul Razak M. In vitro chondrogenesis transformation study of mouse dental pulp stem cells. The Scientific World Journal. 2012;2012.
65.    Niemeyer P, Salzmann G, Feucht M, Pestka J, Porichis S, Ogon P, et al. First-generation versus second-generation autologous chondrocyte implantation for treatment of cartilage defects of the knee: a matched-pair analysis on long-term clinical outcome. International orthopaedics. 2014;38(10):2065-70.
66.    Satué M, Schüler C, Ginner N, Erben RG. Intra-articularly injected mesenchymal stem cells promote cartilage regeneration, but do not permanently engraft in distant organs. Scientific reports. 2019;9(1):1-10.
67.    Fernandes TL, Cortez de SantAnna JP, Frisene I, Gazarini JP, Gomes Pinheiro CC, Gomoll AH, et al. Systematic Review of Human Dental Pulp Stem Cells for Cartilage Regeneration. Tissue engineering Part B, Reviews. 2020;26(1):1-12.
68.    Ogasawara N, Kano F, Hashimoto N, Mori H, Liu Y, Xia L, et al. Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental temporomandibular joint osteoarthritis. Osteoarthritis and Cartilage. 2020;28(6):831-41.
69.    Lo Monaco M, Gervois P, Beaumont J, Clegg P, Bronckaers A, Vandeweerd J-M, et al. Therapeutic potential of dental pulp stem cells and leukocyte-and platelet-rich fibrin for osteoarthritis. Cells. 2020;9(4):980.
70.    Bar JK, Lis-Nawara A, Grelewski PG. Dental pulp stem cell-derived secretome and its regenerative potential. International journal of molecular sciences. 2021;22(21):12018.
71.    Muhammad SA, Nordin N, Hussin P, Mehat MZ, Abu Kasim NH, Fakurazi S. Protective effects of stem cells from human exfoliated deciduous teeth derived conditioned medium on osteoarthritic chondrocytes. PLoS One. 2020;15(9):e0238449.
72.    Anitua E, Troya M, Zalduendo M. Progress in the use of dental pulp stem cells in regenerative medicine. Cytotherapy. 2018;20(4):479-98.
73.    Tuan RS, Chen AF, Klatt BA. Cartilage regeneration. The Journal of the American Academy of Orthopaedic Surgeons. 2013;21(5):303.
74.    Fernandes TL, Shimomura K, Asperti A, Pinheiro CCG, Caetano HVA, Oliveira CRG, et al. Development of a novel large animal model to evaluate human dental pulp stem cells for articular cartilage treatment. Stem cell reviews and reports. 2018;14(5):734-43.
75.    Mata M, Milian L, Oliver M, Zurriaga J, Sancho-Tello M, Llano JJMd, et al. In vivo articular cartilage regeneration using human dental pulp stem cells cultured in an alginate scaffold: a preliminary study. Stem cells international. 2017;2017.
76.    Chen K, Xiong H, Xu N, Shen Y, Huang Y, Liu C. Chondrogenic potential of stem cells from human exfoliated deciduous teeth in vitro and in vivo. Acta Odontologica Scandinavica. 2014;72(8):664-72.
77.    Yu J, He H, Tang C, Zhang G, Li Y, Wang R, et al. Differentiation potential of STRO-1+ dental pulp stem cells changes during cell passaging. BMC cell biology. 2010;11(1):1-7.
78.    Westin CB, Trinca RB, Zuliani C, Coimbra IB, Moraes ÂM. Differentiation of dental pulp stem cells into chondrocytes upon culture on porous chitosan-xanthan scaffolds in the presence of kartogenin. Materials Science and Engineering: C. 2017;80:594-602.
79.    Jafarzadeh H, Moushekhian S, Ghazi N, Vahidi M, Bagherpour A, Shafieian R, et al. Bone Regeneration Effect of Nanochitosan with or without Temporally Controlled Release of Dexamethasone. Journal of Endodontics. 2023;49(5):496-503
80.    Dalirsani Z, Ghazi N, Delavarian Z, Pakfetrat A, Esmaily H, Davaji M, et al. Effects of diode low-level laser therapy on healing of tooth extraction sockets: a histopathological study in diabetic rats. Lasers in Medical Science. 2021;36:1527-34
81.    Sargolzaie N, Kadkhodazadeh M, Ebadian AR, Shafieian R, Pourkaveh S, Naghibi N, et al. Histological Evaluation of Bone Regeneration Using Hydroxyapatite Based Bone Substitute Derived from Antler: An Animal Study. Journal of Long-Term Effects of Medical Implants. 2022;32(1).
82.    Arthur A, Gronthos S. Clinical application of bone marrow mesenchymal stem/stromal cells to repair skeletal tissue. International journal of molecular sciences. 2020. 9759:(24)21
83.    ensen J, Tvedesøe C, Rölfing JH, Foldager CB, Lysdahl H, Kraft DC, et al. Dental pulp-derived stromal cells exhibit a higher osteogenic potency than bone marrow-derived stromal cells in vitro and in a porcine critical-size bone defect model. Sicot-j. 2016;2:16.
84.    Ramamoorthi M, Bakkar M, Jordan J, Tran SD. Osteogenic Potential of Dental Mesenchymal Stem Cells in Preclinical Studies: A Systematic Review Using Modified ARRIVE and CONSORT Guidelines. Stem Cells Int. 2015;2015:37836.
85.    Mortada I, Mortada R. Dental pulp stem cells and osteogenesis: an update. Cytotechnology. 2018;70(5):1479-86.
86.    Tsutsui TW. Dental pulp stem cells: Advances to applications. Stem Cells and Cloning: Advances and Applications. 2020;13:33.
87.    El Moshy S, Radwan IA, Rady D, Abbass M, El-Rashidy AA, Sadek KM, et al. Dental stem cell-derived secretome/conditioned medium: the future for regenerative therapeutic applications. Stem Cells International. 2020;2020.
88.    Li B, Ouchi T, Cao Y, Zhao Z, Men Y. Dental-derived mesenchymal stem cells: state of the art. Frontiers in Cell and Developmental Biology. 2021:1310.
89.    Hiraki T, Kunimatsu R, Nakajima K, Abe T, Yamada S, Rikitake K, et al. Stem cell‐derived conditioned media from human exfoliated deciduous teeth promote bone regeneration. Oral Diseases. 2020;26(2):381-90.
90.    Wang Y, Yuan S, Sun J, Gong Y, Liu S, Guo R, et al. Inhibitory effect of the TSG-6 on the BMP-4/Smad signaling pathway and odonto/osteogenic differentiation of dental pulp stem cells. Biomedicine & Pharmacotherapy. 2020;128:110266.
91.    Zhong T, Gao Y, Qiao H, Zhou H, Liu Y. Elevated osteogenic potential of stem cells from inflammatory dental pulp tissues by Wnt4 overexpression for treating bone defect in rats. Ann Palliat Med. 2020;9:2962-9.
92.    Fujio M, Xing Z, Sharabi N, Xue Y, Yamamoto A, Hibi H, et al. Conditioned media from hypoxic‐cultured human dental pulp cells promotes bone healing during distraction osteogenesis. Journal of tissue engineering and regenerative medicine. 2017;11. 2116-26:(7)
93.    Kumar A, Kumar V, Rattan V, Jha V, Bhattacharyya S. Secretome proteins regulate comparative osteogenic and adipogenic potential in bone marrow and dental stem cells. Biochimie. 2018;155:129-39.
94.    Song M, Finley SD. ERK and Akt exhibit distinct signaling responses following stimulation by pro-angiogenic factors. Cell Communication and Signaling. 2020;18(1):1-19.
95.    Ling LE, Feng L, Liu HC, Wang DS, Shi ZP, Wang JC, et al. The effect of calcium phosphate composite scaffolds on the osteogenic differentiation of rabbit dental pulp stem cells. Journal of biomedical materials research Part A. 2015;103(5):1732-45.
96.    Annibali S, Bellavia D, Ottolenghi L, Cicconetti A, Cristalli MP, Quaranta R, et al. Micro-CT and PET analysis of bone regeneration induced by biodegradable scaffolds as carriers for dental pulp stem cells in a rat model of calvarial "critical size" defect: Preliminary data. Journal of biomedical materials research Part B, Applied biomaterials. 2014;102(4):815-25.
97.    Asutay F, Polat S, Gül M, Subaşı C, Kahraman SA, Karaöz E. The effects of dental pulp stem cells on bone regeneration in rat calvarial defect model: micro-computed tomography and histomorphometric analysis. Archives of oral biology. 2015;60(12):1729-35.
98.    Wongsupa N, Nuntanaranont T, Kamolmattayakul S, Thuaksuban N. Assessment of bone regeneration of a tissue-engineered bone complex using human dental pulp stem cells/poly(ε-caprolactone)-biphasic calcium phosphate scaffold constructs in rabbit calvarial defects. Journal of materials science Materials in medicine. 2017;28(5):77.
99.   Kaigler D, Pagni G, Park CH, Braun TM, Holman LA, Yi E, et al. Stem cell therapy for craniofacial bone regeneration: a randomized, controlled feasibility trial. Cell Transplant. 2013;22. 767-77:(5)
100.  Lee Y-C, Chan Y-H, Hsieh S-C, Lew W-Z, Feng S-W. Comparing the Osteogenic Potentials and Bone Regeneration Capacities of Bone Marrow and Dental Pulp Mesenchymal Stem Cells in a Rabbit Calvarial Bone Defect Model. International journal of molecular sciences. 2019;20(20):5015.
101.  Naji A, Favier B, Deschaseaux F, Rouas-Freiss N, Eitoku M, Suganuma N. Mesenchymal stem/stromal cell function in modulating cell death. Stem cell research & therapy. 2019;10(1):56.
102.  Singer NG, Caplan AI. Mesenchymal stem cells: mechanisms of inflammation. Annual Review of Pathology: Mechanisms of Disease. 2011;6:457-78.
103.  Naji A, Favier B, Deschaseaux F, Rouas-Freiss N, Eitoku M, Suganuma N. Mesenchymal stem/stromal cell function in modulating cell death. Stem cell research & therapy. 2019;10(1):1-12.
104.  Lee YC, Chan YH, Hsieh SC, Lew WZ, Feng SW. Comparing the Osteogenic Potentials and Bone Regeneration Capacities of Bone Marrow and Dental Pulp Mesenchymal Stem Cells in a Rabbit Calvarial Bone Defect Model. International journal of molecular sciences. 2019;20. (20)
105.  d’Aquino R, Papaccio G, Laino G, Graziano A. Dental pulp stem cells: a promising tool for bone regeneration. Stem cell reviews. 2008;4(1):21-6.
106.  Lindvall O, Kokaia Z, Martinez-Serrano A. Stem cell therapy for human neurodegenerative disorders–how to make it work. Nature medicine. 2004;10(7):S42-S50.
107.  Yamamoto A, Matsubara K, Kano F, Sakai K. Analysis of the neuroregenerative activities of mesenchymal stem cells in functional recovery after rat spinal cord injury.  Animal Models for Stem Cell Therapy: Springer; 2014. p. 321-8.
108.  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. Neuroscience Research. 2014;78:16-20.
109.  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. European Journal of Neuroscience. 2004;19(9):2388-98.
110.  Takeyasu M, Nozaki T, Daito M. Differentiation of dental pulp stem cells into a neural lineage. Pediatric Dental Journal. 2006;16(2):154-62.
111.  Karaöz E, Demircan PC, Sağlam Ö, Aksoy A, Kaymaz F, Duruksu G. Human dental pulp stem cells demonstrate better neural and epithelial stem cell properties than bone marrow-derived mesenchymal stem cells. Histochemistry and cell biology. 2011;136(4):455-73.
112.  Chang C-C, Chang K-C, Tsai S-J, Chang H-H, Lin C-P. Neurogenic differentiation of dental pulp stem cells to neuron-like cells in dopaminergic and motor neuronal inductive media. Journal of the Formosan Medical Association. 2014;113(12):956-65.
113.  Kanafi M, Majumdar D, Bhonde R, Gupta P, Datta I. Midbrain cues dictate differentiation of human dental pulp stem cells towards functional dopaminergic neurons. Journal of Cellular Physiology. 2014;229(10):1369-77.
114.  Gervois P, Struys T, Hilkens P, Bronckaers A, Ratajczak J, Politis C, et al. Neurogenic maturation of human dental pulp stem cells following neurosphere generation induces morphological and electrophysiological characteristics of functional neurons. Stem cells and development. 2015;24(3):296-311.
115.  Zhang J, Lian M, Cao P, Bao G, Xu G, Sun Y, et al. Effects of nerve growth factor and basic fibroblast growth factor promote human dental pulp stem cells to neural differentiation. Neurochemical research. 2017;42(4):1015-25.
116.  Chun SY, Soker S, Jang Y-J, Kwon TG, Yoo ES. Differentiation of human dental pulp stem cells into dopaminergic neuron-like cells in vitro. Journal of Korean medical science. 2016;31(2):171-7.
117.  Lu Y, Yuan X, Ou Y, Cai Y, Wang S, Sun Q, et al. Autophagy and apoptosis during adult adipose-derived stromal cells differentiation into neuron-like cells in vitro. Neural Regen Res. 2012;7(16):1205.
118.  Gonmanee T, Thonabulsombat C, Vongsavan K, Sritanaudomchai H. Differentiation of stem cells from human deciduous and permanent teeth into spiral ganglion neuron-like cells. Archives of oral biology. 2018;88:34-41.
119.  Luo L, He Y, Wang X, Key B, Lee BH, Li H, et al. Potential roles of dental pulp stem cells in neural regeneration and repair. Stem cells international. 2018;2018.
120.  Jiang L, Jones S, Jia X. Stem cell transplantation for peripheral nerve regeneration: current options and opportunities. International journal of molecular sciences. 2017;18(1):94.
121.  Pisciotta A, Bertoni L, Vallarola A, Bertani G, Mecugni D, Carnevale G. Neural crest derived stem cells from dental pulp and tooth-associated stem cells for peripheral nerve regeneration. Neural Regen Res. 2020;15(3):373-81.
122.  Mu XD, Liu HH, Li YF, Xiang L, Hu M. [Research progress of dental pulp stem cells for peripheral nerve injury repair]. Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology. 2022;57(2):196-201.
123.  Chen Z-L, Yu W-M, Strickland S. Peripheral regeneration. Annu Rev Neurosci. 2007;30:209-33.
124.  Höke A, Gordon T, Zochodne D, Sulaiman O. A decline in glial cell-line-derived neurotrophic factor expression is associated with impaired regeneration after long-term Schwann cell denervation. Experimental neurology. 2002;173(1):77-85.
125.  Dai L-G, Huang G-S, Hsu S-h. Sciatic nerve regeneration by cocultured Schwann cells and stem cells on microporous nerve conduits. Cell transplantation. 2013;22(11):2029-39.
126.  Faroni A, Mobasseri SA, Kingham PJ, Reid AJ. Peripheral nerve regeneration: experimental strategies and future perspectives. Advanced drug delivery reviews. 2015;82:160-7.
127.  Lee SK, Wolfe SW. Peripheral nerve injury and repair. JAAOS-Journal of the American Academy of Orthopaedic Surgeons. 2000;8(4):243-52.
128.  Wang D, Lyu Y, Yang Y, Zhang S, Chen G, Pan J, et al. Schwann cell-derived EVs facilitate dental pulp regeneration through endogenous stem cell recruitment via SDF-1/CXCR4 axis. Acta biomaterialia. 2022;140:610-24.
129.  Tsuruta T, Sakai K, Watanabe J, Katagiri W, Hibi H. Dental pulp-derived stem cell conditioned medium to regenerate peripheral nerves in a novel animal model of dysphagia. PLoS One. 2018;13(12):e0208938.
130.  Yamamoto T, Osako Y, Ito M, Murakami M, Hayashi Y, Horibe H, et al. Trophic effects of dental pulp stem cells on Schwann cells in peripheral nerve regeneration. Cell Transplantation. 2016;25(1):183-93.
131.  G Mathot F, Shin AY, Van Wijnen AJ. Targeted stimulation of MSCs in peripheral nerve repair. Gene. 2019;710:17-23.
132.  Sultan N, Amin LE, Zaher AR, Scheven BA, Grawish ME. Dental pulp stem cells: Novel cell-based and cell-free therapy for peripheral nerve repair. World Journal of Stomatology. 2019;7(1):1-19.
133.  Sultan N, Amin LE, Zaher AR, Grawish ME, Scheven BA. Neurotrophic effects of dental pulp stem cells on trigeminal neuronal cells. Scientific Reports. 2020;10(1):1-13.
134.  Carnevale G, Pisciotta A, Riccio M, Bertoni L, De Biasi S, Gibellini L, et al. Human dental pulp stem cells expressing STRO-1, c-kit and CD34 markers in peripheral nerve regeneration. Journal of Tissue Engineering and Regenerative Medicine. 2018;12(2):e774-e85.
135.  Martens W, Sanen K, Georgiou M, Struys T, Bronckaers A, Ameloot M, et al. Human dental pulp stem cells can differentiate into Schwann cells and promote and guide neurite outgrowth in an aligned tissue‐engineered collagen construct in vitro. The FASEB Journal. 2014;28(4):1634-43.
136. Gervois P, Wolfs E, Dillen Y, Hilkens P, Ratajczak J, Driesen R, et al. Paracrine maturation and migration of SH-SY5Y cells by dental pulp stem cells. Journal of Dental Research. 2017;96(6):654-62.
137.  Khazaeipour Z, Norouzi-Javidan A, Kaveh M, Khanzadeh Mehrabani F, Kazazi E, Emami-Razavi S-H. Psychosocial outcomes following spinal cord injury in Iran. The journal of spinal cord medicine. 2014;37. 338-45:(3)
138.  Yamada Y, Nakamura-Yamada S, Kusano K, Baba S. Clinical Potential and Current Progress of Dental Pulp Stem Cells for Various Systemic Diseases in Regenerative Medicine: A Concise Review. International journal of molecular sciences. 2019;20.(5).
139.  Duncan T, Valenzuela M. Alzheimer’s disease, dementia, and stem cell therapy. Stem cell research & therapy. 2017;8(1):1-9.
140.  Wang F, Jia Y, Liu J, Zhai J, Cao N, Yue W, et al. Dental pulp stem cells promote regeneration of damaged neuron cells on the cellular model of Alzheimer's disease. Cell Biology International. 2017;41(6):639-50.
141.  Apel C, Forlenza O, De Paula V, Talib L, Denecke B, Eduardo C, et al. The neuroprotective effect of dental pulp cells in models of Alzheimer’s and Parkinson’s disease. Journal of neural transmission. 2009;116(1):71-8.
142.  Ahmed NE-MB, Murakami M, Hirose Y, Nakashima M. Therapeutic potential of dental pulp stem cell secretome for Alzheimer’s disease treatment: an in vitro study. Stem cells international. 20. 2016:16
143.  Yamada Y, Nakamura-Yamada S, Kusano K, Baba S. Clinical Potential and Current Progress of Dental Pulp Stem Cells for Various Systemic Diseases in Regenerative Medicine: A Concise Review. International journal of molecular sciences. 2019;20. 1132:(5)
144.  Ahmed Nel M, Murakami M, Hirose Y, Nakashima M. Therapeutic Potential of Dental Pulp Stem Cell Secretome for Alzheimer's Disease Treatment: An In Vitro Study. Stem Cells Int. 2016;2016:8102478.
145. Xiao Z, Lei T, Liu Y, Yang Y, Bi W, Du H. The potential therapy with dental tissue-derived mesenchymal stem cells in Parkinson’s disease. Stem cell research & therapy. 2021;12(1):1-11.
146.  Wang Y, Chen S, Yang D, Le W-d. Stem cell transplantation: a promising therapy for Parkinson’s disease. Journal of neuroimmune pharmacology. 2007;2(3):243-50.
147.  Majumdar D, Kanafi M, Bhonde R, Gupta P, Datta I. Differential neuronal plasticity of dental pulp stem cells from exfoliated deciduous and permanent teeth towards dopaminergic neurons. Journal of cellular physiology. 2016;231(9):2048-63.
148.   Gnanasegaran N, Govindasamy V, Simon C, Gan QF, Vincent‐Chong VK, Mani V, et al. Effect of dental pulp stem cells in MPTP‐induced old‐aged mice model. European journal of clinical investigation. 2017;47(6):403-1
149.  Zhang N, Lu X, Wu S, Li X, Duan J, Chen C, et al. Intrastriatal transplantation of stem cells from human exfoliated deciduous teeth reduces motor defects in Parkinsonian rats. Cytotherapy. 2018;20(5):670-86.
150.  Földes A, Kádár K, Kerémi B, Gyires K, S Zádori Z, Varga GV. Mesenchymal stem cells of dental origin-their potential for antiinflammatory and regenerative actions in brain and gut damage. Current neuropharmacology. 2016;14(8):914-34.
151.  Nosrat IV, Widenfalk J, Olson L, Nosrat CA. Dental pulp cells produce neurotrophic factors, interact with trigeminal neurons in vitro, and rescue motoneurons after spinal cord injury. Developmental biology. 2001;238(1):120-32.
152.  Yang C, Li X, Sun L, Guo W, Tian W. Potential of human dental stem cells in repairing the complete transection of rat spinal cord. Journal of neural engineering. 2017;14(2):026005.
153.  Zhang J, Lu X, Feng G, Gu Z, Sun Y, Bao G, et al. Chitosan scaffolds induce human dental pulp stem cells to neural differentiation: potential roles for spinal cord injury therapy. Cell and tissue research. 2016;366(1):129-42.
154.  Man RC, Sulaiman N, Idrus RBH, Ariffin SHZ, Wahab RMA, Yazid MD. Insights into the Effects of the Dental Stem Cell Secretome on Nerve Regeneration: Towards Cell-Free Treatment. Stem cells international. 2019;2019.
155.  Kolar MK, Itte VN, Kingham PJ, Novikov LN, Wiberg M, Kelk P. The neurotrophic effects of different human dental mesenchymal stem cells. Scientific reports. 2017;7(1):1-12.
156.  Greening DW, Simpson RJ. Understanding extracellular vesicle diversity–current status. Expert review of proteomics. 2018;15(11):887-910.
157.  Ferro F, Spelat R, Baheney CS. Dental pulp stem cell (DPSC) isolation, characterization, and differentiation. Methods in molecular biology (Clifton, NJ). 2014;1210:91-115.
158.  Liang C, Liao L, Tian W. Stem Cell-based Dental Pulp Regeneration: Insights From Signaling Pathways. Stem Cell Rev Rep. 2021;17(4):1251-63.
159.  Liu C, Hu F, Jiao G, Guo Y, Zhou P, Zhang Y, et al. Dental pulp stem cell-derived exosomes suppress M1 macrophage polarization through the ROS-MAPK-NFκB P65 signaling pathway after spinal cord injury. Journal of nanobiotechnology. 2022;20(1):65.
160.  Alksne M, Kalvaityte M, Simoliunas E, Gendviliene I, Barasa P, Rinkunaite I, et al. Dental pulp stem cell-derived extracellular matrix: autologous tool boosting bone regeneration. Cytotherapy. 2022;24(6):597-607.
161.  Gao Y, Tian Z, Liu Q, Wang T, Ban LK, Lee HH, et al. Neuronal Cell Differentiation of Human Dental Pulp Stem Cells on Synthetic Polymeric Surfaces Coated With ECM Proteins. Front Cell Dev Biol. 2022;10:893241.
162.  Yamagishi H, Shigematsu K. Perspectives on Stem Cell-Based Regenerative Medicine with a Particular Emphasis on Mesenchymal Stem Cell Therapy. JMA journal. 2022;5(1):36-43.
163.  Gong P, Tian Q, He Y, He P, Wang J, Guo Y, et al. Dental pulp stem cell transplantation facilitates neuronal neuroprotection following cerebral ischemic stroke. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;15:113234
164.  Calabrese EJ, Agathokleous E, Dhawan G, Kapoor R, Calabrese V. Human dental pulp stem cells and hormesis. Ageing research reviews. 2022;73:101540.