Advances and Perspectives in Dental Pulp Stem Cell Based Neuroregeneration Therapies

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Apr 3

PMID 33805573

Citations 33

Authors

Jon Luzuriaga

Yurena Polo

Oier Pastor-Alonso

Beatriz Pardo-Rodriguez

Aitor Larranaga

Fernando Unda

Jose-Ramon Sarasua

Jose Ramon Pineda

Gaskon Ibarretxe

Affiliations

Soon will be listed here.

Abstract

Human dental pulp stem cells (hDPSCs) are some of the most promising stem cell types for regenerative therapies given their ability to grow in the absence of serum and their realistic possibility to be used in autologous grafts. In this review, we describe the particular advantages of hDPSCs for neuroregenerative cell therapies. We thoroughly discuss the knowledge about their embryonic origin and characteristics of their postnatal niche, as well as the current status of cell culture protocols to maximize their multilineage differentiation potential, highlighting some common issues when assessing neuronal differentiation fates of hDPSCs. We also review the recent progress on neuroprotective and immunomodulatory capacity of hDPSCs and their secreted extracellular vesicles, as well as their combination with scaffold materials to improve their functional integration on the injured central nervous system (CNS) and peripheral nervous system (PNS). Finally, we offer some perspectives on the current and possible future applications of hDPSCs in neuroregenerative cell therapies.

Citing Articles

Intrinsic and extrinsic modulators of human dental pulp stem cells: advancing strategies for tissue engineering applications.

Kavakebian F, Rezapour A, Seyedebrahimi R, Farsani M, Fakhr M, Zare Jalise S Mol Biol Rep. 2025; 52(1):190.

PMID: 39899148 DOI: 10.1007/s11033-025-10281-0.

Dental Pulp Stem Cells Attenuate Early Brain Injury After Subarachnoid Hemorrhage via miR-26a-5p/PTEN/AKT Pathway.

He P, Zhang H, Wang J, Guo Y, Tian Q, Liu C Neurochem Res. 2025; 50(2):91.

PMID: 39883266 DOI: 10.1007/s11064-025-04340-y.

RNA sequencing reveals key factors modulating TNFα-stimulated odontoblast-like differentiation of dental pulp stem cells.

Irfan M, Kim J, Sreekumar S, Chung S bioRxiv. 2025; .

PMID: 39868289 PMC: 11761799. DOI: 10.1101/2025.01.09.632294.

Functional differentiation of human dental pulp stem cells into neuron-like cells exhibiting electrophysiological activity.

Pardo-Rodriguez B, Baraibar A, Manero-Roig I, Luzuriaga J, Salvador-Moya J, Polo Y Stem Cell Res Ther. 2025; 16(1):10.

PMID: 39849603 PMC: 11756023. DOI: 10.1186/s13287-025-04134-7.

Bone Regeneration with Dental Pulp Stem Cells in an Experimental Model.

Hamad-Alrashid H, Muntion S, Sanchez-Guijo F, Borrajo-Sanchez J, Parreno-Manchado F, Garcia-Cenador M J Pers Med. 2024; 14(11).

PMID: 39590567 PMC: 11595977. DOI: 10.3390/jpm14111075.

References

Panikkar B, Smith N, Brown P . Reflexive research ethics in fetal tissue xenotransplantation research. Account Res. 2012; 19(6):344-69. PMC: 3689847. DOI: 10.1080/08989621.2012.728910. View

de Jong O, van Balkom B, Schiffelers R, Bouten C, Verhaar M . Extracellular vesicles: potential roles in regenerative medicine. Front Immunol. 2014; 5:608. PMC: 4253973. DOI: 10.3389/fimmu.2014.00608. View

Nosrat I, Widenfalk J, Olson L, Nosrat C . Dental pulp cells produce neurotrophic factors, interact with trigeminal neurons in vitro, and rescue motoneurons after spinal cord injury. Dev Biol. 2002; 238(1):120-32. DOI: 10.1006/dbio.2001.0400. View

Tian J, Zhao Y, Jin Z, Lu C, Tang Q, Xiang Q . Synthesis and characterization of Poloxamer 188-grafted heparin copolymer. Drug Dev Ind Pharm. 2010; 36(7):832-8. DOI: 10.3109/03639040903520983. View

Gronthos S, Brahim J, Li W, Fisher L, Cherman N, Boyde A . Stem cell properties of human dental pulp stem cells. J Dent Res. 2002; 81(8):531-5. DOI: 10.1177/154405910208100806. View

Qiao Y, Agboola O, Hu X, Wu Y, Lei L . Tumorigenic and Immunogenic Properties of Induced Pluripotent Stem Cells: a Promising Cancer Vaccine. Stem Cell Rev Rep. 2020; 16(6):1049-1061. PMC: 7494249. DOI: 10.1007/s12015-020-10042-5. View

Albashari A, He Y, Zhang Y, Ali J, Lin F, Zheng Z . Thermosensitive bFGF-Modified Hydrogel with Dental Pulp Stem Cells on Neuroinflammation of Spinal Cord Injury. ACS Omega. 2020; 5(26):16064-16075. PMC: 7346236. DOI: 10.1021/acsomega.0c01379. View

Ciregia F, Urbani A, Palmisano G . Extracellular Vesicles in Brain Tumors and Neurodegenerative Diseases. Front Mol Neurosci. 2017; 10:276. PMC: 5583211. DOI: 10.3389/fnmol.2017.00276. View

Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M . Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999; 5(4):434-8. DOI: 10.1038/7434. View

10.

Gnanasegaran N, Govindasamy V, Simon C, Gan Q, Vincent-Chong V, Mani V . Effect of dental pulp stem cells in MPTP-induced old-aged mice model. Eur J Clin Invest. 2017; 47(6):403-414. DOI: 10.1111/eci.12753. View

11.

Martens W, Sanen K, Georgiou M, Struys T, Bronckaers A, Ameloot M . 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. FASEB J. 2013; 28(4):1634-43. PMC: 4046066. DOI: 10.1096/fj.13-243980. View

12.

Kanafi M, Majumdar D, Bhonde R, Gupta P, Datta I . Midbrain cues dictate differentiation of human dental pulp stem cells towards functional dopaminergic neurons. J Cell Physiol. 2014; 229(10):1369-77. DOI: 10.1002/jcp.24570. View

13.

Pisciotta A, Bertani G, Bertoni L, Di Tinco R, De Biasi S, Vallarola A . Modulation of Cell Death and Promotion of Chondrogenic Differentiation by Fas/FasL in Human Dental Pulp Stem Cells (hDPSCs). Front Cell Dev Biol. 2020; 8:279. PMC: 7242757. DOI: 10.3389/fcell.2020.00279. View

14.

Eugen-Olsen J, Andersen O, Linneberg A, Ladelund S, Hansen T, Langkilde A . Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population. J Intern Med. 2010; 268(3):296-308. DOI: 10.1111/j.1365-2796.2010.02252.x. View

15.

Cetinalp Demircan P, Eker Sariboyaci A, Unal Z, Gacar G, Subasi C, Karaoz E . Immunoregulatory effects of human dental pulp-derived stem cells on T cells: comparison of transwell co-culture and mixed lymphocyte reaction systems. Cytotherapy. 2011; 13(10):1205-20. DOI: 10.3109/14653249.2011.605351. View

16.

Ozdemir A, Ozgul Ozdemir R, Kirmaz C, Eker Sariboyaci A, Unal Halbutogllari Z, Ozel C . The paracrine immunomodulatory interactions between the human dental pulp derived mesenchymal stem cells and CD4 T cell subsets. Cell Immunol. 2016; 310:108-115. DOI: 10.1016/j.cellimm.2016.08.008. View

17.

Kawabori M, Weintraub A, Imai H, Zinkevych I, McAllister P, Steinberg G . Cell Therapy for Chronic TBI: Interim Analysis of the Randomized Controlled STEMTRA Trial. Neurology. 2021; 96(8):e1202-e1214. PMC: 8055341. DOI: 10.1212/WNL.0000000000011450. View

18.

Isola G, Polizzi A, Alibrandi A, Williams R, Leonardi R . Independent impact of periodontitis and cardiovascular disease on elevated soluble urokinase-type plasminogen activator receptor (suPAR) levels. J Periodontol. 2020; 92(6):896-906. DOI: 10.1002/JPER.20-0242. View

19.

Sasaki R, Aoki S, Yamato M, Uchiyama H, Wada K, Ogiuchi H . PLGA artificial nerve conduits with dental pulp cells promote facial nerve regeneration. J Tissue Eng Regen Med. 2011; 5(10):823-30. DOI: 10.1002/term.387. View

20.

Solleiro-Villavicencio H, Rivas-Arancibia S . Effect of Chronic Oxidative Stress on Neuroinflammatory Response Mediated by CD4T Cells in Neurodegenerative Diseases. Front Cell Neurosci. 2018; 12:114. PMC: 5934485. DOI: 10.3389/fncel.2018.00114. View