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Angiogenic Potential and Its Modifying Interventions in Dental Pulp Stem Cells: a Systematic Review

Abstract

Background

Dental pulp stem cells (DPSCs) have been reported to have a pro-angiogenic effect indicative of the inherent property. Angiogenesis is a phenomenon crucial for wound healing, tissue regeneration, and vascularization of engineered scaffolds. Therefore, it is crucial to explore the angiogenic potential and the contributing factors in order to exploit this potential in stem cell research and tissue engineering.

Aim

To systematically review the literature on the angiogenic potential of DPSCs as well as to explore the effect of external environmental interventions on the angiogenic potential.

Methods

Three databases, PubMed, MEDLINE, and Cochrane, were systematically reviewed for literature with a suitable inclusion criterion. The data was screened for quantitative data for use in a meta-analysis.

Result

Overall, the studies indicated that DPSCs possess an inherent angiogenic potential that can be enhanced through external stimulation. The experimental methodology lacked consistency, and thus no quantitative data could be extracted for meta-analysis.

Conclusion

DPSCs are pro-angiogenic, which can be enhanced through external manipulation, making them a feasible option for use in tissue engineering and regenerative medicine. Consistency in experimental methodology is required in order to quantitatively analyze the angiogenic potential of DPSCs.

Lay Summary

The process of angiogenesis plays a central role in wound healing and tissue regeneration. Dental pulp stem cells or DPSCs are an excellent source of regenerative stem cells with immunomodulatory as well as immunomodulatory and renewal potential. Inherent properties of DPSCs can be utilized to enhance the process of wound healing and engineer tissue under laboratory conditions. The angiogenic potential of DPSCs can be enhanced through stimulation with conditioned media, growth factors, antibiotics, and dental fillings. Hypoxia and 3D cell culture would also benefit via the enhancement of the angiogenic property of DPSCs. Two broad categories of articles were included in this systematic review: directly assessing the angiogenic potential of DPSCs and studies assessing the effect of interventions on this potential.

Owing to their angiogenic potential, DPSCs can contribute greatly to the field of regenerative medicine in which cell growth is primarily hampered by the scarcity of oxygen supply due to the absence of blood vessels. Furthermore, DPSCs’ angiogenic potential invites new research avenues to assess the mechanism associated with angiogenesis and their use in therapeutics and regenerative medicine.

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Data Availability

All data presented in the study are available in the table provided. Any further inquiries may be directed to the corresponding author.

References

  1. Nuti N, Corallo C, Chan BMF, Ferrari M, Gerami-Naini B. Multipotent differentiation of human dental pulp stem cells: a literature review. Stem cell Rev reports. 2016;12(5):511–23. https://doi.org/10.1007/S12015-016-9661-9.

    CAS  Article  Google Scholar 

  2. Martens W, Bronckaers A, Politis C, Jacobs R, Lambrichts I. Dental stem cells and their promising role in neural regeneration: an update. Clin Oral Investig. 2013;17(9):1969–83. https://doi.org/10.1007/S00784-013-1030-3.

    CAS  Article  Google Scholar 

  3. Rodríguez-Lozano FJ, Insausti CL, Meseguer L, Ramírez MC, Martínez S, Moraleda JM. Tissue engineering with dental pulp stem cells: isolation, characterization, and osteogenic differentiation. J Craniofac Surg. 2012;23(6). https://doi.org/10.1097/SCS.0B013E31825E4E16

  4. Rodríguez Lozano FJ, Moraleda JM. Mesenchymal dental pulp stem cells: a new tool in sinus lift. J Craniofac Surg. 2011;22(2):774–5. https://doi.org/10.1097/SCS.0b013e318208ba61.

    Article  Google Scholar 

  5. Merckx G, Hosseinkhani B, Kuypers S, et al. Angiogenic effects of human dental pulp and bone marrow-derived mesenchymal stromal cells and their extracellular vesicles. Cells. 2020;9(2). https://doi.org/10.3390/CELLS9020312

  6. D’Aquino R, Papaccio G, Laino G, Graziano A. Dental pulp stem cells: a promising tool for bone regeneration. Stem Cell Rev. 2008;4(1):21–6. https://doi.org/10.1007/S12015-008-9013-5.

    Article  Google Scholar 

  7. Nam H, Kim GH, Bae YK, et al. Angiogenic capacity of dental pulp stem cell regulated by SDF-1 α-CXCR4 axis. Stem Cells Int. 2017;2017. https://doi.org/10.1155/2017/8085462

  8. Badodekar N, Sharma A, Patil V, et al. Angiogenesis induction in breast cancer: a paracrine paradigm. Cell Biochem Funct. 2021;39(7):860–73. https://doi.org/10.1002/cbf.3663.

    CAS  Article  Google Scholar 

  9. Caviedes-Bucheli J, Gomez-Sosa JF, Azuero-Holguin MM, Ormeño-Gomez M, Pinto-Pascual V, Munoz HR. Angiogenic mechanisms of human dental pulp and their relationship with substance P expression in response to occlusal trauma. Int Endod J. 2017;50(4):339–51. https://doi.org/10.1111/IEJ.12627.

    CAS  Article  Google Scholar 

  10. de Cara SPHM, Origassa CST, de Sá Silva F, et al. Angiogenic properties of dental pulp stem cells conditioned medium on endothelial cells in vitro and in rodent orthotopic dental pulp regeneration. Heliyon. 2019;5(4). https://doi.org/10.1016/J.HELIYON.2019.E01560

  11. Aranha AMF, Zhang Z, Neiva KG, Costa CAS, Hebling J, Nör JE. Hypoxia enhances the angiogenic potential of human dental pulp cells. J Endod. 2010;36(10):1633–7. https://doi.org/10.1016/J.JOEN.2010.05.013.

    Article  Google Scholar 

  12. Dissanayaka WL, Zhang C. The role of vasculature engineering in dental pulp regeneration. J Endod. 2017;43(9S):S102–6. https://doi.org/10.1016/J.JOEN.2017.09.003.

    Article  Google Scholar 

  13. Bronckaers A, Hilkens P, Fanton Y, et al. Angiogenic properties of human dental pulp stem cells. PLoS ONE. 2013;8(8):e71104. https://doi.org/10.1371/JOURNAL.PONE.0071104.

    CAS  Article  Google Scholar 

  14. Hilkens P, Fanton Y, Martens W, et al. Pro-angiogenic impact of dental stem cells in vitro and in vivo. Stem Cell Res. 2014;12(3):778–90. https://doi.org/10.1016/J.SCR.2014.03.008.

    CAS  Article  Google Scholar 

  15. Hilkens P, Bronckaers A, Ratajczak J, Gervois P, Wolfs E, Lambrichts I. The angiogenic potential of DPSCs and SCAPs in an in vivo model of dental pulp regeneration. Stem Cells Int. 2017;2017. https://doi.org/10.1155/2017/2582080

  16. Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4(1):148–60. https://doi.org/10.1186/2046-4053-4-1.

    Article  Google Scholar 

  17. Bronckaers A, Hilkens P, Fanton Y, et al. Angiogenic properties of human dental pulp stem cells. PLoS One. 2013;8(8). https://doi.org/10.1371/JOURNAL.PONE.0071104

  18. Lin CY, Tsai MS, Kuo PJ, et al. 2,3,5,4’-Tetrahydroxystilbene-2-O-β-d-glucoside promotes the effects of dental pulp stem cells on rebuilding periodontal tissues in experimental periodontal defects. J Periodontol. 2021;92(2):306–16. https://doi.org/10.1002/JPER.19-0563.

    CAS  Article  Google Scholar 

  19. Nam H, Kim GH, Bae YK, et al. Angiogenic capacity of dental pulp stem cell regulated by SDF-1 α-CXCR4 axis. Stem Cells Int. 2017;2017. https://doi.org/10.1155/2017/8085462

  20. Osman A, Gnanasegaran N, Govindasamy V, et al. Basal expression of growth-factor-associated genes in periodontal ligament stem cells reveals multiple distinctive pathways. Int Endod J. 2014;47(7):639–51. https://doi.org/10.1111/IEJ.12200.

    CAS  Article  Google Scholar 

  21. Makino E, Nakamura N, Miyabe M, et al. Conditioned media from dental pulp stem cells improved diabetic polyneuropathy through anti-inflammatory, neuroprotective and angiogenic actions: cell-free regenerative medicine for diabetic polyneuropathy. J Diabetes Investig. 2019;10(5):1199. https://doi.org/10.1111/JDI.13045.

    CAS  Article  Google Scholar 

  22. Piva E, Tarlé SA, Nör JE, et al. Dental pulp tissue regeneration using dental pulp stem cells isolated and expanded in human serum. J Endod. 2017;43(4):568–74. https://doi.org/10.1016/J.JOEN.2016.11.018.

    Article  Google Scholar 

  23. Sanen K, Martens W, Georgiou M, Ameloot M, Lambrichts I, Phillips J. Engineered neural tissue with Schwann cell differentiated human dental pulp stem cells: potential for peripheral nerve repair? J Tissue Eng Regen Med. 2017;11(12):3362–72. https://doi.org/10.1002/TERM.2249.

    CAS  Article  Google Scholar 

  24. Gong T, Xu J, Heng B, et al. EphrinB2/EphB4 signaling regulates DPSCs to induce sprouting angiogenesis of endothelial cells. J Dent Res. 2019;98(7):803–12. https://doi.org/10.1177/0022034519843886.

    CAS  Article  Google Scholar 

  25. Huang X, Qiu W, Pan Y, et al. Exosomes from LPS-stimulated hDPSCs activated the angiogenic potential of HUVECs in vitro. Stem Cells Int. 2021;2021. https://doi.org/10.1155/2021/6685307

  26. Angelopoulos I, Brizuela C, Khoury M. Gingival mesenchymal stem cells outperform haploidentical dental pulp-derived mesenchymal stem cells in proliferation rate, migration ability, and angiogenic potential. Cell Transplant. 2018;27(6):967–78. https://doi.org/10.1177/0963689718759649.

    Article  Google Scholar 

  27. Aksel H, Huang GTJ. Human and swine DPSCs form vascular-like network after angiogenic differentiation in comparison to endothelial cells — a quantitative analysis. J Endod. 2017;43(4):588. https://doi.org/10.1016/J.JOEN.2016.11.015.

    Article  Google Scholar 

  28. Gandia C, Armiñan A, García-Verdugo JM, et al. Human dental pulp stem cells improve left ventricular function, induce angiogenesis, and reduce infarct size in rats with acute myocardial infarction. Stem Cells. 2008;26(3):638–45. https://doi.org/10.1634/STEMCELLS.2007-0484.

    Article  Google Scholar 

  29. Paino F, La NM, Giuliani A, et al. Human DPSCs fabricate vascularized woven bone tissue: a new tool in bone tissue engineering. Clin Sci (Lond). 2017;131(8):699–713. https://doi.org/10.1042/CS20170047.

    CAS  Article  Google Scholar 

  30. Chiu HY, Lin CH, Hsu CY, Yu J, Hsieh CH, Shyu WC. IGF1R + dental pulp stem cells enhanced neuroplasticity in hypoxia-ischemia model. Mol Neurobiol. 2017;54(10):8225–41. https://doi.org/10.1007/S12035-016-0210-Y.

    CAS  Article  Google Scholar 

  31. Bu NU, Lee HS, Lee BN, et al. In vitro characterization of dental pulp stem cells cultured in two microsphere-forming culture plates. J Clin Med. 2020;9(1). https://doi.org/10.3390/JCM9010242

  32. Alghutaimel H, Yang X, Drummond B, Nazzal H, Duggal M, Raïf E. Investigating the vascularization capacity of a decellularized dental pulp matrix seeded with human dental pulp stem cells: in vitro and preliminary in vivo evaluations. Int Endod J. 2021;54(8):1300–16. https://doi.org/10.1111/IEJ.13510.

    CAS  Article  Google Scholar 

  33. Silva GO, Zhang Z, Cucco C, Oh M, Camargo CHR, Nör JE. Lipoprotein receptor-related protein 6 signaling is necessary for vasculogenic differentiation of human dental pulp stem cells. J Endod. 2017;43(9S):S25–30. https://doi.org/10.1016/J.JOEN.2017.06.006.

    Article  Google Scholar 

  34. Saghiri MA, Asatourian A, Sorenson CM, Sheibani N. Mice dental pulp and periodontal ligament endothelial cells present different angiogenic phenotypes. Tissue Cell. 2018;50:31. https://doi.org/10.1016/J.TICE.2017.11.004.

    CAS  Article  Google Scholar 

  35. Zhou H, Li X, Wu RX, et al. Periodontitis-compromised dental pulp stem cells secrete extracellular vesicles carrying miRNA-378a promote local angiogenesis by targeting Sufu to activate the Hedgehog/Gli1 signalling. Cell Prolif. 2021;54(5). https://doi.org/10.1111/CPR.13026

  36. Pisciotta A, Riccio M, Carnevale G, et al. Stem cells isolated from human dental pulp and amniotic fluid improve skeletal muscle histopathology in mdx/SCID mice. Stem Cell Res Ther. 2015;6(1). https://doi.org/10.1186/S13287-015-0141-Y

  37. Zhou H, Li X, Yin Y, et al. The proangiogenic effects of extracellular vesicles secreted by dental pulp stem cells derived from periodontally compromised teeth. Stem Cell Res Ther. 2020;11(1). https://doi.org/10.1186/S13287-020-01614-W

  38. Watanabe M, Ohyama A, Ishikawa H, Tanaka A. Three-dimensional bone formation including vascular networks derived from dental pulp stem cells in vitro. Hum Cell. 2019;32(2):114–24. https://doi.org/10.1007/S13577-018-00228-Y.

    CAS  Article  Google Scholar 

  39. Ullah I, Park JM, Kang YH, et al. Transplantation of human dental pulp-derived stem cells or differentiated neuronal cells from human dental pulp-derived stem cells identically enhances regeneration of the injured peripheral nerve. Stem Cells Dev. 2017;26(17):1247–57. https://doi.org/10.1089/SCD.2017.0068.

    CAS  Article  Google Scholar 

  40. Yamamoto T, Osako Y, Ito M, et al. Trophic effects of dental pulp stem cells on Schwann cells in peripheral nerve regeneration. Cell Transplant. 2016;25(1):183–93. https://doi.org/10.3727/096368915X688074.

    Article  Google Scholar 

  41. Janebodin K, Zeng Y, Buranaphatthana W, Ieronimakis N, Reyes M. VEGFR2-dependent angiogenic capacity of pericyte-like dental pulp stem cells. J Dent Res. 2013;92(6):524–31. https://doi.org/10.1177/0022034513485599.

    CAS  Article  Google Scholar 

  42. Zhang Z, Nör F, Oh M, Cucco C, Shi S, Nör JE. Wnt/β-catenin signaling determines the vasculogenic fate of postnatal mesenchymal stem cells. Stem Cells. 2016;34(6):1576–87. https://doi.org/10.1002/STEM.2334.

    CAS  Article  Google Scholar 

  43. Osman A, Gnanasegaran N, Govindasamy V, et al. Basal expression of growth-factor-associated genes in periodontal ligament stem cells reveals multiple distinctive pathways. Int Endod J. 2014;47(7):639–51. https://doi.org/10.1111/IEJ.12200.

    CAS  Article  Google Scholar 

  44. Angelopoulos I, Brizuela C, Khoury M. Gingival mesenchymal stem cells outperform haploidentical dental pulp-derived mesenchymal stem cells in proliferation rate, migration ability, and angiogenicpotential. Cell Transplant. 2018;27(6):967. https://doi.org/10.1177/0963689718759649.

    Article  Google Scholar 

  45. Saghiri MA, Asatourian A, Sorenson CM, Sheibani N. Mice dental pulp and periodontal ligament endothelial cells exhibit different proangiogenic properties. Tissue Cell. 2018;50:31–6. https://doi.org/10.1016/J.TICE.2017.11.004.

    CAS  Article  Google Scholar 

  46. Sanen K, Martens W, Georgiou M, Ameloot M, Lambrichts I, Phillips J. Engineered neural tissue with Schwann cell differentiated human dental pulp stem cells: potential for peripheral nerve repair? J Tissue Eng Regen Med. 2017;11(12):3362–72. https://doi.org/10.1002/TERM.2249.

    CAS  Article  Google Scholar 

  47. Piva E, Tarlé SA, Nör JE, et al. Dental pulp tissue regeneration using dental pulp stem cells isolated and expanded in human serum. J Endod. 2017;43(4):568–74. https://doi.org/10.1016/J.JOEN.2016.11.018.

    Article  Google Scholar 

  48. Silva GO, Zhang Z, Cucco C, Oh M, Camargo CHR, Nör JE. Lipoprotein receptor-related protein 6 signaling is necessary for vasculogenic differentiation of human dental pulp stem cells. J Endod. 2017;43(9S):S25–30. https://doi.org/10.1016/J.JOEN.2017.06.006.

    Article  Google Scholar 

  49. Gutiérrez-Quintero JG, Durán Riveros JY, Martínez Valbuena CA, Pedraza Alonso S, Munévar J, Viafara-García S. Critical-sized mandibular defect reconstruction using human dental pulp stem cells in a xenograft model-clinical, radiological, and histological evaluation. Oral Maxillofac Surg. 2020;24(4):485–93. https://doi.org/10.1007/S10006-020-00862-7.

    Article  Google Scholar 

  50. Collignon AM, Lesieur J, Anizan N, et al. Early angiogenesis detected by PET imaging with 64 Cu-NODAGA-RGD is predictive of bone critical defect repair. Acta Biomater. 2018;82:111–21. https://doi.org/10.1016/J.ACTBIO.2018.10.008.

    CAS  Article  Google Scholar 

  51. Nakayama H, Iohara K, Hayashi Y, Okuwa Y, Kurita K, Nakashima M. Enhanced regeneration potential of mobilized dental pulp stem cells from immature teeth. Oral Dis. 2017;23(5):620–8. https://doi.org/10.1111/ODI.12619.

    CAS  Article  Google Scholar 

  52. 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. Acta Biomater. 2016;33:225–34. https://doi.org/10.1016/J.ACTBIO.2016.01.032.

    CAS  Article  Google Scholar 

  53. El-Fiqi A, Mandakhbayar N, Bin Jo S, Knowles JC, Lee JH, Kim HW. Nanotherapeutics for regeneration of degenerated tissue infected by bacteria through the multiple delivery of bioactive ions and growth factor with antibacterial/angiogenic and osteogenic/odontogenic capacity. Bioact Mater. 2020;6(1):123–36. https://doi.org/10.1016/J.BIOACTMAT.2020.07.010.

    Article  Google Scholar 

  54. Li X, Ma C, Xie X, Sun H, Liu X. Pulp regeneration in a full-length human tooth root using a hierarchical nanofibrous microsphere system. Acta Biomater. 2016;35:57–67. https://doi.org/10.1016/J.ACTBIO.2016.02.040.

    CAS  Article  Google Scholar 

  55. Kawamura R, Hayashi Y, Murakami H, Nakashima M. EDTA soluble chemical components and the conditioned medium from mobilized dental pulp stem cells contain an inductive microenvironment, promoting cell proliferation, migration, and odontoblastic differentiation. Stem Cell Res Ther. 2016;7(1):1–14. https://doi.org/10.1186/S13287-016-0334-Z.

    Article  Google Scholar 

  56. Boyle M, Chun C, Strojny C, et al. Chronic inflammation and angiogenic signaling axis impairs differentiation of dental-pulp stem cells. PLoS One. 2014;9(11). https://doi.org/10.1371/JOURNAL.PONE.0113419

  57. Dissanayaka WL, Zhan X, Zhang C, Hargreaves KM, Jin L, Tong EHY. Coculture of dental pulp stem cells with endothelial cells enhances osteo-/odontogenic and angiogenic potential in vitro. J Endod. 2012;38(4):454–63. https://doi.org/10.1016/J.JOEN.2011.12.024.

    Article  Google Scholar 

  58. Dubey N, Xu J, Zhang Z, Nör JE, Bottino MC. Comparative evaluation of the cytotoxic and angiogenic effects of minocycline and clindamycin: an in vitro study. J Endod. 2019;45(7):882–9. https://doi.org/10.1016/J.JOEN.2019.04.007.

    Article  Google Scholar 

  59. Zhu L, Dissanayaka WL, Zhang C. Dental pulp stem cells overexpressing stromal-derived factor-1α and vascular endothelial growth factor in dental pulp regeneration. Clin Oral Investig. 2019;23(5):2497–509. https://doi.org/10.1007/S00784-018-2699-0.

    Article  Google Scholar 

  60. Olcay K, Taşli PN, Güven EP, et al. Effect of a novel bioceramic root canal sealer on the angiogenesis-enhancing potential of assorted human odontogenic stem cells compared with principal tricalcium silicate-based cements. J Appl Oral Sci. 2020;28. https://doi.org/10.1590/1678-7757-2019-0215

  61. Li X, Hou J, Wu B, Chen T, Luo A. Effects of platelet-rich plasma and cell coculture on angiogenesis in human dental pulp stem cells and endothelial progenitor cells. J Endod. 2014;40(11):1810–4. https://doi.org/10.1016/J.JOEN.2014.07.022.

    Article  Google Scholar 

  62. Lu W, Xu W, Li J, Chen Y, Pan Y, Wu B. Effects of vascular endothelial growth factor and insulin growth factor-1 on proliferation, migration, osteogenesis and vascularization of human carious dental pulp stem cells. Mol Med Rep. 2019;20(4):3924–32. https://doi.org/10.3892/MMR.2019.10606.

    CAS  Article  Google Scholar 

  63. Qu C, Brohlin M, Kingham PJ, Kelk P. Evaluation of growth, stemness, and angiogenic properties of dental pulp stem cells cultured in cGMP xeno-/serum-free medium. Cell Tissue Res. 2020;380(1):93–105. https://doi.org/10.1007/S00441-019-03160-1.

    CAS  Article  Google Scholar 

  64. Schertl P, Volk J, Perduns R, et al. Impaired angiogenic differentiation of dental pulp stem cells during exposure to the resinous monomer triethylene glycol dimethacrylate. Dent Mater. 2019;35(1):144–55. https://doi.org/10.1016/J.DENTAL.2018.11.006.

    CAS  Article  Google Scholar 

  65. Delle Monache S, Martellucci S, Clementi L, et al. In vitro conditioning determines the capacity of dental pulp stem cells to function as pericyte-like cells. Stem Cells Dev. 2019;28(10):695–706. https://doi.org/10.1089/SCD.2018.0192.

    CAS  Article  Google Scholar 

  66. Xu JG, Gong T, Wang YY, et al. Inhibition of TGF-β signaling in SHED enhances endothelial differentiation. J Dent Res. 2018;97(2):218–25. https://doi.org/10.1177/0022034517733741.

    CAS  Article  Google Scholar 

  67. Pankajakshan D, Voytik-Harbin SL, Nör JE, Bottino MC. Injectable highly tunable oligomeric collagen matrices for dental tissue regeneration. ACS Appl bio Mater. 2020;3(2). https://doi.org/10.1021/ACSABM.9B00944

  68. Gardin C, Ferroni L, Piattelli A, Sivolella S, Zavan B, Mijiritsky E. Non-washed resorbable blasting media (NWRBM) on titanium surfaces could enhance osteogenic properties of MSCs through increase of miRNA-196a and VCAM1. Stem cell Rev reports. 2016;12(5):543–52. https://doi.org/10.1007/S12015-016-9669-1.

    CAS  Article  Google Scholar 

  69. Spina A, Montella R, Liccardo D, et al. NZ-GMP Approved serum improve hDPSC osteogenic commitment and increase angiogenic factor expression. Front Physiol. 2016;7(AUG). https://doi.org/10.3389/FPHYS.2016.00354

  70. Abdik H, Avşar Abdik E, Demirci S, Doğan A, Turan D, Şahin F. The effects of bisphosphonates on osteonecrosis of jaw bone: a stem cell perspective. Mol Biol Rep. 2019;46(1):763–76. https://doi.org/10.1007/S11033-018-4532-X.

    CAS  Article  Google Scholar 

  71. Luzuriaga J, Irurzun J, Irastorza I, Unda F, Ibarretxe G, Pineda JR. Vasculogenesis from human dental pulp stem cells grown in matrigel with fully defined serum-free culture media. Biomedicines. 2020;8(11):1–19. https://doi.org/10.3390/BIOMEDICINES8110483.

    Article  Google Scholar 

  72. An L, Shen S, Wang L, et al. TNF-alpha increases angiogenic potential in a co-culture system of dental pulp cells and endothelial cells. Braz Oral Res. 2019;33. https://doi.org/10.1590/1807-3107BOR-2019.VOL33.0059

  73. Dissanayaka WL, Han Y, Zhang L, Zou T, Zhang C. Bcl-2 overexpression and hypoxia synergistically enhance angiogenic properties of dental pulp stem cells. Int J Mol Sci. 2020;21(17):1–19. https://doi.org/10.3390/IJMS21176159.

    Article  Google Scholar 

  74. Zhang M, Jiang F, Zhang X, et al. The effects of platelet-derived growth factor-BB on human dental pulp stem cells mediated dentin-pulp complex regeneration. Stem Cells Transl Med. 2017;6(12):2126–34. https://doi.org/10.1002/SCTM.17-0033.

    CAS  Article  Google Scholar 

  75. Dissanayaka WL, Hargreaves KM, Jin L, Samaranayake LP, Zhang C. The interplay of dental pulp stem cells and endothelial cells in an injectable peptide hydrogel on angiogenesis and pulp regeneration in vivo. Tissue Eng Part A. 2015;21(3–4):550–63. https://doi.org/10.1089/TEN.TEA.2014.0154.

    CAS  Article  Google Scholar 

  76. Takeuchi N, Hayashi Y, Murakami M, et al. Similar in vitro effects and pulp regeneration in ectopic tooth transplantation by basic fibroblast growth factor and granulocyte-colony stimulating factor. Oral Dis. 2015;21(1):113–22. https://doi.org/10.1111/ODI.12227.

    CAS  Article  Google Scholar 

  77. Núñez-Toldrà R, Montori S, Bosch B, Hupa L, Atari M, Miettinen S. S53P4 bioactive glass inorganic ions for vascularized bone tissue engineering by dental pulp pluripotent-like stem cell cocultures. Tissue Eng Part A. 2019;25(17–18):1213–24. https://doi.org/10.1089/TEN.TEA.2018.0256.

    Article  Google Scholar 

  78. Jin GZ, Kim HW. Co-culture of human dental pulp stem cells and endothelial cells using porous biopolymer microcarriers: a feasibility study for bone tissue engineering. Tissue Eng Regen Med. 2017;14(4):393–401. https://doi.org/10.1007/S13770-017-0061-2.

    CAS  Article  Google Scholar 

  79. Mangano C, Paino F, d’Aquino R, et al. Human dental pulp stem cells hook into biocoral scaffold forming an engineered biocomplex. PLoS One. 2011;6(4). https://doi.org/10.1371/JOURNAL.PONE.0018721

  80. Aranha AMF, Zhang Z, Neiva KG, Costa CAS, Hebling J, Nör JE. Hypoxia enhances the angiogenic potential of human dental pulp cells. J Endod. 2010;36(10):1633–7. https://doi.org/10.1016/J.JOEN.2010.05.013.

    Article  Google Scholar 

  81. Liu C, Yang G, Zhou M, et al. Magnesium ammonium phosphate composite cell-laden hydrogel promotes osteogenesis and angiogenesis in vitro. ACS Omega. 2021;6(14):9449–59. https://doi.org/10.1021/ACSOMEGA.0C06083.

    CAS  Article  Google Scholar 

  82. Dou L, Yan Q, Liang P, Zhou P, Zhang Y, Ji P. iTRAQ-based proteomic analysis exploring the influence of hypoxia on the proteome of dental pulp stem cells under 3D culture. Proteomics. 2018;18(3–4). https://doi.org/10.1002/PMIC.201700215

  83. Aksel H, Öztürk SA, Ulubayram K. VEGF/BMP-2 loaded three-dimensional model for enhanced angiogenic and odontogenic potential of dental pulp stem cells. Int Endod J. 2018;51(4):420–30. https://doi.org/10.1111/IEJ.12869.

    CAS  Article  Google Scholar 

  84. Xia K, Chen Z, Chen J, et al. RGD- and VEGF-mimetic peptide epitope-functionalized self-assembling peptide hydrogels promote dentin-pulp complex regeneration. Int J Nanomedicine. 2020;15:6631–47. https://doi.org/10.2147/IJN.S253576.

    CAS  Article  Google Scholar 

  85. Dissanayaka WL, Zhu L, Hargreaves KM, Jin L, Zhang C. Scaffold-free prevascularized microtissue spheroids for pulp regeneration. J Dent Res. 2014;93(12):1296–303. https://doi.org/10.1177/0022034514550040.

    CAS  Article  Google Scholar 

  86. Campagnoli C, Roberts IAG, Kumar S, Bennett PR, Bellantuono I, Fisk NM. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood. 2001;98(8):2396–402. https://doi.org/10.1182/BLOOD.V98.8.2396.

    CAS  Article  Google Scholar 

  87. Gao F, Chiu SM, Motan DAL, et al. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis. 2016;7(1). https://doi.org/10.1038/CDDIS.2015.327

  88. Li B, Chen X, Jin Y. Tooth and dental pulp regeneration. A Roadmap to Nonhematopoietic Stem Cell-Based Ther From Bench to Clin. Published online January 2019:367–392. https://doi.org/10.1016/B978-0-12-811920-4.00015-X

  89. Potdar PD, Jethmalani YD. Human dental pulp stem cells: applications in future regenerative medicine. World J Stem Cells. 2015;7(5):839. https://doi.org/10.4252/WJSC.V7.I5.839.

    Article  Google Scholar 

  90. Mattei V, Martellucci S, Pulcini F, Santilli F, Sorice M, Delle MS. Regenerative potential of DPSCs and revascularization: direct, paracrine or autocrine effect? Stem cell Rev reports. 2021;17(5):1635–46. https://doi.org/10.1007/S12015-021-10162-6.

    CAS  Article  Google Scholar 

  91. Sieveking DP, Ng MKC. Cell therapies for therapeutic angiogenesis: back to the bench. Vasc Med. 2009;14(2):153–66. https://doi.org/10.1177/1358863X08098698.

    Article  Google Scholar 

  92. Gorecka J, Kostiuk V, Fereydooni A, et al. The potential and limitations of induced pluripotent stem cells to achieve wound healing. Stem Cell Res Ther. 2019;10(1). https://doi.org/10.1186/S13287-019-1185-1

  93. Malhotra N. Induced pluripotent stem (iPS) cells in dentistry: a review. Int J Stem Cells. 2016;9(2):176–85. https://doi.org/10.15283/IJSC16029.

    CAS  Article  Google Scholar 

  94. Lee HY, Hong IS. Double-edged sword of mesenchymal stem cells: cancer-promoting versus therapeutic potential. Cancer Sci. 2017;108(10):1939–46. https://doi.org/10.1111/CAS.13334.

    CAS  Article  Google Scholar 

  95. Zakrzewski W, Dobrzyński M, Szymonowicz M, Rybak Z. Stem cells: past, present, and future. Stem Cell Res Ther. 2019;10(1):1–22. https://doi.org/10.1186/S13287-019-1165-5/FIGURES/8.

    Article  Google Scholar 

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Badodekar, N., Mishra, S., Telang, G. et al. Angiogenic Potential and Its Modifying Interventions in Dental Pulp Stem Cells: a Systematic Review. Regen. Eng. Transl. Med. (2022). https://doi.org/10.1007/s40883-022-00270-1

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Keywords

  • Dental pulp stem cells
  • Angiogenesis
  • Stem cells
  • Tissue engineering
  • Vasculogenesis
  • Dental pulp