Mesenchymal stem cells from human umbilical cord decrease inflammation and increase vascularization of induced apical periodontitis model in diabetes mellitus rat

Authors

DOI:

https://doi.org/10.1590/

Keywords:

Diabetes mellitus, Animal model, Inflammation, Vascularization, Mesenchymal stem cells

Abstract

Objectives: to evaluate inflammation and vascularization in a model of apical periodontitis in diabetic Wistar rats through histopathological examination of blood vessels and immunohistochemical examination of interleukin 1b (IL-1b) and tumor necrosis factor-a (TNF-a). Methodology: Diabetes was induced in 20 Wistar rats using multiple low-dose injections of streptozotocin (STZ) until blood glucose levels stabilized above 300 mg/dL, confirmed by glucometer. Under anesthesia, apical periodontitis was induced in the right mandibular first molars. After preparing the access cavity and extirpating pulp and canal, the teeth were left open. Apical periodontitis was projected seven days afterwards and the Wistar rats were assigned in random into four groups, each group consisting of five rats. The first group (C14) was euthanized 14 days post-induction, while the second group (C28) was euthanized 28 days later, serving as controls. The third group (T14) received mesenchymal stem cells from human umbilical cords and was euthanized after 14 days, while the fourth group (T28) received mesenchymal stem cells from human umbilical cord and was euthanized after 28 days. The number of blood vessels and the expressions of IL-1b and TNF-a were analyzed. Data were evaluated with ANOVA and by Tukey's HSD test, with significance at p<0.05. Results: Both control and treatment groups showed a significant increase in vascularization in the apical periodontal area of apical periodontitis in the control and treatment groups at 14 and 28 days (p<0.05). A significant reduction of IL-1b and TNF-a levels was found in the mesenchymal stem cells treatment groups when compared to control groups (p<0.05). Conclusion: Our findings support the use of mesenchymal stem cells from human umbilical cords to decrease inflammation and increase vascularization in an induced apical periodontitis model in diabetes mellitus Wistar rats.

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References

- Saghiri MA, Aminsobhani M, Gutmann JL, Kawai T, Nath D, Hirschberg C. Effect of diabetes on rotary instrumentation of dentin. J Endod. 2021;47(08):1301-7. doi: 10.1016/j.joen.2021.03.019

» https://doi.org/10.1016/j.joen.2021.03.019

- Kuntjoro M, Hendrijantini N, Prasetyo EP, Legowo D, Sitalaksmi RM, Agustono B, et al. Human umbilical cord mesenchymal stem cells accelerate and increase implant osseointegration in diabetic rats. J Appl Oral Sci. 2023;31:e20220375. doi: 10.1590/1678-7757-2022-0375

» https://doi.org/10.1590/1678-7757-2022-0375

- Samanta S. Glycated hemoglobin and subsequent risk of microvascular and macrovascular complications. Indian J Med Sci. 2021;73(2):230-8. doi: 10.25259/IJMS_16_2020

» https://doi.org/10.25259/IJMS_16_2020

- Alqadi SF. Diabetes mellitus and its influence on oral health: review. Diabetes Metab Syndr Obes. 2024;17:107-20. doi: 10.2147/DMSO.S426671

» https://doi.org/10.2147/DMSO.S426671

- Kuntjoro M, Agustono B, Prasetyo EP, Salim S, Rantam FA, Hendrijantini N. The effect of advanced glycation end products (AGEs) on human umbilical cord mesenchymal stem cells (hUCMSCs) with regard to osteogenesis and calcification. Res J Pharm Tech. 2021;14(8):4019-24. doi: 10.52711/0974-360X.2021.00696

» https://doi.org/10.52711/0974-360X.2021.00696

- Zhang CC, Liu YJ, Yang WD, Zhang QN, Zha MZ, Wen SH, et al. Morphological changes of the root apex in anterior teeth with periapical periodontitis: an in-vivo study. BMC Oral Health. 2022;22:31. doi: 10.1186/s12903-022-02062-z

» https://doi.org/10.1186/s12903-022-02062-z

- Tsai HC, Chen CH, Mochly-Rosen D, Li YCE, Chen MH. The role of alcohol, LPS toxicity, and ALDH2 in dental bony defects. Bony Defects. Biomolecules. 2021;11(5):651. doi: 10.3390/biom11050651

» https://doi.org/10.3390/biom11050651

- Prasetyo EP, Sampoerno G, Juniarti DE, Cahyani F, Saraswati W, Kuntjoro M, et al. Effect of lipopolysaccharide-induced apical periodontitis in diabetes mellitus rats on periapical inflammation. Eur J Dent. 2023;17:1146-52. doi: 10.1055/s-0042-1758790

» https://doi.org/10.1055/s-0042-1758790

- Romero-Diaz C, Duarte-Montero D, Gutierrez-Romero SA, Mendivil CO. Diabetes and bone fragility. Diabetes Ther. 2021;12:71-86. doi: 10.1007/s13300-020-00964-1

» https://doi.org/10.1007/s13300-020-00964-1

- Ateeq H, Zia A, Husain Q, Khan MS, Ahmad M. Effect of inflammation on bones in diabetic patients with periodontitis via RANKL/OPG system – a review. J Diabetes Metab Disord. 2022;21(1):1003-9. doi: 10.1007/s40200-021-00960-7

» https://doi.org/10.1007/s40200-021-00960-7

- Hendrijantini N, Kuntjoro M, Agustono B, Ari MD, Kurdi A, Mundiratri K, et al. Bone formation and mineralization around the implant in osteoporotic animal models enhanced by mesenchymal stem cells. Dent J (Majalah Kedokteran Gigi) 2024;57(2):d 91-6. doi: 10.20473/j.djmkg.v57.i2.p91-96

» https://doi.org/10.20473/j.djmkg.v57.i2.p91-96

- Prasetyo EP, Kuntjoro M, Goenharto S, Juniarti DE, Cahyani F, Hendrijantini N, et al. Calcium hydroxide increases human umbilical cord mesenchymal stem cells expressions of apoptotic protease-activating factor-1, caspase-3 and caspase-9. Clin Cosmet Investig Dent 2021;13:59-65. doi: 10.2147/CCIDE.S284240

» https://doi.org/10.2147/CCIDE.S284240

- Kuntjoro M, Prasetyo EP, Cahyani F, Kamadjaja MJ, Hendrijantini N, Laksono H, et al. Lipopolysaccharide's cytotoxicity on human umbilical cord mesenchymal stem cells. Pesqui Bras Odontopediatria Clin Integr. 2020;20(1-7):e0048. doi: 10.1590/pboci.2020.153

» https://doi.org/10.1590/pboci.2020.153

- Prasetyo EP, Kuntjoro M, Cahyani F, Goenharto S, Saraswati W, Juniarti DE, et al. Calcium hydroxide upregulates interleukin-10 expression in time dependent exposure and induces osteogenic differentiation of human umbilical cord mesenchymal stem cells. Int J Pharm Res. 2021;13(1):140-5. doi: 10.31838/ijpr/2021.13.01.023

» https://doi.org/10.31838/ijpr/2021.13.01.023

- Ariestania V, Hendrijantini N, Prahasanti C, Prasetyo E, Kuntjoro M, Sari RP, et al. Cytotoxicity of HA-TCP scaffold on human umbilical cord mesenchymal stem cells using MTT assay. Int J Integr Eng. 2022;14(2):80-5. doi: 10.30880/ijie.2022.14.012

» https://doi.org/10.30880/ijie.2022.14.012

- Kuntjoro M, Hendrijantini N, Prasetyo EP, Agustono B, Sitalaksmi RM, Hendrianto E, et al. Cobalt chloride as a hypoxia mimicking agent induced HIF-1a and mTOR expressions of human umbilical cord mesenchymal stem cells. Pesqui Bras Odontopediatria Clin Integr. 2024;24:e220128. doi: 10.1590/pboci.2024.020

» https://doi.org/10.1590/pboci.2024.020

- Prasetyo EP, Widjiastuti I, Cahyani F, Kuntjoro M, Hendrijantini N, Hariyani N, et al. Cytotoxicity of calcium hydroxide on human umbilical cord mesenchymal stem cells. Pesqui Bras Odontopediatria Clin Integr. 2020;20:e0044. doi: 10.1590/pboci.2020.141

» https://doi.org/10.1590/pboci.2020.141

- Prieto AK, Gomes-Filho JE, Azuma MM, Sivieri-Araujo G, Narciso LG, Souza JC, et al. Influence of apical periodontitis on stress oxidative parameters in diabetic rats. J Endod. 2017;43(10):1651-6. doi: 10.1016/j.joen.2017.05.014

» https://doi.org/10.1016/j.joen.2017.05.014

- Aminoshariae A, Kulild JC, Mickel A, Fouad AF. Association between systemic diseases and endodontic outcome: a systematic review. J Endod. 2017;43(4):514-9. doi: 10.1016/j.joen.2016.11.008

» https://doi.org/10.1016/j.joen.2016.11.008

- Leon-Lopez M, Cabanillas-Balsera D, Martin-Gonzalez J, Diaz-Flores V, Areal-Quecuty V, Crespo-Gallardo I, et al. Prevalence of root canal treatments among diabetic patients: systematic review and meta-analysis. Appl Sci 2023;13:5957. doi: 10.3390/app13105957

» https://doi.org/10.3390/app13105957

- Nagendrababu V, Kishen A, Murray PE, Nekoofar MH, Figueiredo JA, Priya E, et al. PRIASE 2021 guidelines for reporting animal studies in endodontology: a consensus-based development. Int Endod J 2021;54(6):848-57. doi: 10.1111/iej.13477

» https://doi.org/10.1111/iej.13477

- Cordero CB, Santander GM, Gonzalez DU, Quezada A, Silva CI, Vasquez C, et al. Allogenic cellular therapy in a mature tooth with apical periodontitis and accidental root perforation: a case report. J Endod 2020;46(2):1920-7. doi: 10.1016/j.joen.2020.04.007

» https://doi.org/10.1016/j.joen.2020.04.007

- Gheibi S, Kashfi K, Ghasemi A. A practical guide for induction of type-2 diabetes in rat: incorporating a high-fat diet and streptozotocin. Biomed Pharmacother. 2017;95:605-13. doi: 10.1016/j.biopha.2017.08.098

» https://doi.org/10.1016/j.biopha.2017.08.098

- Hasegawa T, Suresh VV, Yahata Y, Nakano M, Suzuki S, Suzuki S, et al. Inhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation. Sci Rep. 2021;11:2613. doi: 10.1038/s41598-021-82167-7.

» https://doi.org/10.1038/s41598-021-821677

- Daryabor G, Atashzar MR, Kabelitz D, Meri S, Kalantar K. The effects of type 2 diabetes mellitus on organ metabolism and the immune system. Front Immunol. 2020;11:1582. doi: 10.3389/fimmu.2020.01582

» https://doi.org/10.3389/fimmu.2020.01582

- Cheng R, Wu Z, Li M, Shao M, Hu T. Interleukin 1b is a potential therapeutic target for periodontitis: a narrative review. Int J Oral Sci 2020;12:2. doi: 10.1038/s41368-019-0068-8

» https://doi.org/10.1038/s41368-019-0068-8

- Park HC, Quan H, Zhu T, Kim Y, Kim B, Yang HC. The effect of M1 and M2 macrophages on odontogenic differentiation of human dental pulp cells. J Endod 2017;43(4):596-601. doi: 10.1016/j.joen.2016.11.003

» https://doi.org/10.1016/j.joen.2016.11.003

- Diniz JM, Espaladori MC, Silva ME, Brito LC, Vieira LQ, Sobrinho AP. Immunological profile of periapical endodontic infection in patients undergoing haematopoietic transplantation. Clin Oral Investig 2021;25:1403-10. doi: 10.1007/s00784-020-03448-5

» https://doi.org/10.1007/s00784-020-03448-5

- Segura-Egea JJ, Cabanillas-Balsera D, Martin-Gonzalez J, Cintra LT. Impact of systemic health on treatment outcomes in endodontics. Int Endod J. 2023;56(Suppl. 2):219-35. doi: 10.1111/iej.13789

» https://doi.org/10.1111/iej.13789

- Berniyanti T, Wening GR, Palupi R, Setyowati D, Putri CR. Low levels of tumor necrosis factor-a will prevent periodontitis exacerbation in type 2 diabetes mellitus. Eur J Dent 2022;16(02):443-8. doi: 10.1055/s-0041-1739442

» https://doi.org/10.1055/s-0041-1739442

- Ge Y, Huang M, Yao YM. Autophagy and proinflammatory cytokines: interactions and clinical implications. Cytokine Growth Factor Rev. 2018;43:38-46. doi: 10.1016/j.cytogfr.2018.07.001

» https://doi.org/10.1016/j.cytogfr.2018.07.001

- Braz-Silva PH, Bergamini ML, Mardegan AP, Rosa CS, Hasseus B, Jonasson P. Inflammatory profile of chronic apical periodontitis: a literature review. Acta Odontol Scand. 2019;77(3):173-80. doi: 10.1080/00016357.2018.1521005

» https://doi.org/10.1080/00016357.2018.1521005

- Nascimento IV, Rodrigues MI, Isaias PH, Barros-Silva PG, Sousa FB, Alves AP, et al. Chronic systemic corticosteroid therapy influences the development of pulp necrosis and experimental apical periodontitis, exacerbating the inflammatory process and bone resorption in rats. Int Endod J. 2022;55:646-59. doi: 10.1111/iej.13724

» https://doi.org/10.1111/iej.13724

- Brizuela C, Meza G, Urrejola D, Quezada MA, Concha G, Ramirez V, et al. Cell-based regenerative endodontics for treatment of periapical lesions: a randomized, controlled phase I/II clinical trial. J Dent Res. 2020;99(5):523-9. doi: 10.1177/0022034520913242

» https://doi.org/10.1177/0022034520913242

- Xiao E, Mattos M, Vieira GH, Chen S, Correa JD, Wu Y, et al. Diabetes enhances IL-17 expression and alters the oral microbiome to increase its pathogenicity. Cell Host Microbe. 2017;22:120-8. doi: 10.1016/j.chom.2017.06.014

» https://doi.org/10.1016/j.chom.2017.06.014

- Jakovljevic A, Knezevic A, Karalic D, Soldatovic I, Popovic B, Milasin J, et al. Pro-inflammatory cytokine levels in human apical periodontitis: correlation with clinical and histological findings. Aust Endod J. 2015;41:72-7. doi: 10.1111/aej.12072

» https://doi.org/10.1111/aej.12072

- Kamal MM, Kassem DH. Therapeutic potential of Wharton's jelly mesenchymal stem cells for diabetes: achievements and challenges. Front Cell Dev Biol. 2020;8:16. doi: 10.3389/fcell.2020.00016

» https://doi.org/10.3389/fcell.2020.00016

- Yang J, Chen Z, Pan D, Li H, Shen J. Umbilical cord-derived mesenchymal stem cell-derived exosomes combined Pluronic F127 hydrogel promote chronic diabetic wound healing and complete skin regeneration. Int J Nanomedicine. 2020;15:5911-26. doi: 10.2147/IJN.S249129

» https://doi.org/10.2147/IJN.S249129

- He J, Kong D, Yang Z, Guo R, Amponsah AE, Feng B, et al. Clinical efficacy on glycemic control and safety of mesenchymal stem cells in patients with diabetes mellitus: systematic review and meta-analysis of RCT data. PLoS One. 2021;16(3):e0247662. doi: 10.1371/journal.pone.0247662

» https://doi.org/10.1371/journal.pone.0247662

- Sui BD, Hu CH, Zheng CX, Shuai Y, He XN, Gao PP, et al. Recipient glycemic micro-environments govern therapeutic effects of mesenchymal stem cell infusion on osteopenia. Theranostics 2017;7(5):1225-44. doi: 10.7150/thno.18181

» https://doi.org/10.7150/thno.18181

- Nagendrababu V, Segura-Egea JJ, Fouad AF, Pulikkotil SJ, Dummer PM. Association between diabetes and the outcome of root canal treatment in adults: an umbrella review. Int Endod J 2020;53:455-66. doi: 10.1111/iej.13253

» https://doi.org/10.1111/iej.13253

- Wang HW, Lai EH, Yang CN, Lin SK, Hong CY, Yang H, et al. Intracanal metformin promotes healing of apical periodontitis via suppressing inducible nitric oxide synthase expression and monocyte recruitment. J Endod. 2020;46(1):65-73. doi: 10.1016/j.joen.2019.10.001

» https://doi.org/10.1016/j.joen.2019.10.001

- Siavash M, Tabbakhian M, Sabzghabaee AM, Razavi N. Severity of gastrointestinal side effects of metformin tablet compared to metformin capsule in type 2 diabetes mellitus patients. J Res Phar Practice. 2017;6(2):73-6. doi: 10.4103/jrpp.JRPP_17_2

» https://doi.org/10.4103/jrpp.JRPP_17_2

- Cabanillas-Balsera D, Martin-Gonzales J, Montero-Miralles P, Sanchez-Domingues B, Jimenez-Sanchez MC, Segura-Egea JJ. Association between diabetes and non-retention of root filled teeth: a systematic review and meta-analysis. Int Endod J. 2019;52(3):297-306. doi: 10.1111/iej.13011

» https://doi.org/10.1111/iej.13011

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Published

2024-11-04

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Original Articles

How to Cite

Prasetyo, E. P., Juniarti, D. E., Kuntjoro, M., Hendrijantini, N., Putra, A. A., Oktaria, W., Hutapea, Z. F. R. D., & Tjendronegoro, E. (2024). Mesenchymal stem cells from human umbilical cord decrease inflammation and increase vascularization of induced apical periodontitis model in diabetes mellitus rat. Journal of Applied Oral Science, 32, e2024-0225. https://doi.org/10.1590/