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The Efficacy of Human Dental Pulp Stem Cells in regenerating Submandibular Gland Defects in Diabetic Wistar Rats (Rattus novergicus)


Affiliations
1 Universitas Airlangga, Surabaya, Indonesia
2 Orthodontics Department, Universitas Airlangga, Surabaya, Indonesia
3 Oral Medicine Department, Universitas Airlangga, Surabaya, Indonesia
4 Periodontics Department, Universitas Airlangga, Surabaya, Indonesia
5 Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, Indonesia
6 Virology and Immunology Laboratory, Microbiology Department, Universitas Airlangga, Surabaya, Indonesia
     

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Chronic hyperglicemia in Diabetes Mellitus caused microangiopathy in salivary gland. Human Dental Pulp Stem Cells (HDPSCs) suspected can regenerate the defect. The aim of this study was to analyze the efficacy of HDPSCs in stimulating angiogenesis, acinar cell numbers and Transforming Growth Factor-β (TGF-β) serum to regenerate submandibular gland defects in diabetic Wistar rats. Twenty-four male Wistar (250-350 g) rats 3-months-old were used. Rats were divided into 4 groups (n=6 each: a positive control group on Day 7 (DM) (C+7), a positive control group on Day 14 (DM) (C+14), a treatment group on Day 7 (DM+5.105 HDPSCs transplantation intraglandular) (T7) and a treatment group on Day 14 (DM+5.105 HDPSCs transplantation intraglandular) (T14). Wistar Rats were administered with 30 mg of Streptozotocin per kg of bodyweight to induce Diabetes Mellitus (DM). Histopathological examination with HE staining was performed to analyse neovascularization and acinar cell numbers. ELISA was performed to measure TGF-β serum. Statistical analysis used: A Tukey HSD or Bonferroni test after ANOVA or Kruskal Wallis test was performed (p<0.05) based on a Saphiro Wilk and Levene’s test (p>0.05). The highest acinar cell number was found in the T7 group [513.167±136.17] with no significant difference [p=0.136, p<0.05]. The highest capillaries were found in T14 [10.667±4.54] and TGF-β serum level [168.87±37.38] with significant difference [p=0.006; p<0.05] and [p=0.008, p<0.05]. HDPSCs can regenerate submandibular gland defects in Diabetic Wistar rats by stimulating angiogenesis, acinar cells number and TGF – β serum.

Keywords

Human Dental Pulp Stem Cells, Submandibular Gland Defect, Diabetes Mellitus, Acinar Cells, Angiogenesis, Transforming Growth Factor-β.
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  • Nwauche KT, Monago Comfort C, Frank I. Management of Diabetes Mellitus with Combined Therapy of Reducdyn and Metformin in Streptozotocin-induced Diabetic Rats. Research J. Pharm. and Tech. 2014; 7(1): 39-43.

  • International Diabetes Federation. Diabetes Atlas eight edition. Available from: URL: http://www.diabetesatlas.org, 2017.

  • Basha SKH, Subramanian S. Antidyslipidemic Property of Annona Squamosa Leaves Extract Studied in Streptozotocin-Induced Experimental Diabetes in Rats. Asian J. Research Chem. 2012; 5(2): 234-238.

  • Shrivastava SR, Shrivastava PS, Ramasamy J. Role of self-care in management of diabetes mellitus. J Diabet and Metab Dis. 2013; 12: 14.

  • Ranadheer CP, Praveen D, Vijey AMA. Prospective Study on Incidence of Dyslipidemia in Diabetes Mellitus. Research J. Pharm. and Tech. 2017; 10(2):431-433.

  • Kumari MS, Babu MK, Sulthana R, Srinivas M, Prasanthi C. Diabetes Mellitus: Present status and Drug Therapy Updates. Research J. Pharm. and Tech. 2014; 7(1):84-94.

  • Gupta A, Chaturvedi P, Shrivastava S. K., Dubey P.K. Glitazones for the Treatment of Diabetes Type-2. Asian J. Research Chem. 2012; 5(2): 164-170.

  • Salvayre NS, Pamplona A, Otin P. Hyperglycemia and Glycation in Diabetic Complications. Antioxid Redox Signal. 2009; 3071-3109.

  • Pintor RM, Casanas Elizabeth, Serrano JG, Serrano J, Ramirez L, Arriba L, Hernandez G. Review Article Xerostomia, Hyposalivation, and Salivary Flow in Diabetes Patients. Journal of Diabetes Research. 2012; 1-2.

  • Randhika T, Ranganathan K. Original Research: Salivary Output in Type 2 Diabetic Patients. Oral Maxillofacial Pathology Journal. 2014; 1-2.

  • Agarwal R, Lakshmi T. Salivary Enzymes as Biomarkers for Periodontitis – An Update. Research J. Pharm. and Tech. 2014; 7(1):98-100.

  • Fatimah RN. Diabetes Mellitus Type 2. Faculty of Medicine Lampung University. 2015; 2-3.

  • Soeharno H. The Effect of Glycemic Control on Periodontal Disease in Diabetic Patient. International Dental Journal. 2013; 1-2.

  • Gusbi GAM, Mohamed S, El-Hafez SA. Submandibular Glands as an Evident of the Effects of Antioxidant on Alloxan Induced Diabetic Rats. World Journal of Medical Sciences. 2014; 210-216.

  • Tao H, Han Z, Han ZC, Li Z: Review Article Proangiogenic Features of Mesenchymal Stem Cells and Their Therapeutic Applications. Stem Cells International. 2016; 1314709: 1-11.

  • Pedersen T, Blois A, Xue Y, Xing Z, Sun Y, Wistrand A, Lorens J, Fristad I, Leknes K, Mustafa K. Stem Cell Research and Therapy: Mesenchymal Stem Cells induce Endothelial Cell Quiescence and Promote Capillary Formation. Norway: Biomed Central. Stem Cell Res Ther. 2014; 17(5): 1-23.

  • Gao F, Chiu SM, Motan DA. Mesenchymal stem cell and immunomodulation: current status and future prospects. Cell Death and Disease. 2016; 7(1): 62.

  • Miran S, Mitsiadis TA, Pagella P. Innovative dental stem cell-based researchapproaches: the future of dentistry. Stem Cells International. 2016; 1 (1): 1-10.

  • Nugraha AP, Narmada IB, Ernawati DS, Dinaryanti A, Hendrianto E, Ihsan IS, Riawan W, Rantam FA. Osteogenic potential of gingival stromal progenitor cells cultures in platelet rich fibrin is predicted by core-binding factor subunit-α1/Sox9 expression ratio (in vitro). F1000Research. 2018; 7(1134): 4.

  • Furman BL. Streptozotocin-Induced Diabetic Models in Mice and Rats. Curr. Protoc. Pharmacol. 2015; 70 (5): 5471-54720.

  • Knas M, Maciejzcyk M, Daniszewska I, Klimiuk A, Matczuk J, Kolodziej U, Waszkiel D, Ladny JR, Zendzian-Piotrowska M, Zalewska A. Oxidative Damage to the Salivary Glands of Rats with Streptozotocin-Induced Diabetes-Temporal Study: Oxidative Stress and Diabetic Salivary Glands. Journal of Diabetes Research. 2016; 3: 1-13.

  • Mahmoud EF, Mahmoud MF: Effect of Pomegranate Peel Extract on Submandibular Salivary Glands of Streptozotocin-Induced Diabetes in Rats: Histological, Immunohistochemical and Ultrastructural Study. Journal of Advances in Biology and Biotechnology. 2017; 13 (3): 1-15.

  • Jang JH, Lee HW, Shin HW, Kang MK, Park SH, Kim E. In vitro characterization of human dental pulp stem cells isolated by three different methods. Restorative Dentistry and Endodontics. 2016; 41 (4): 283-95.

  • Luisi SB, Filho MSA, Pranke P. Isolation, immunophenotypic characterization and pluripotency of dental pulp stem cells. Dent Oral Craniofac Res. 2017; 3(5):1-3.

  • Rantam FA, Nugraha AP, Narmada IB, Ernawati DS, Widodo ADW, Lestari P, Dinaryanti A, Hendrianto E, Ihsan IS, Susilowati H, Ertanti N, Karsari D. Gingival Mesenchymal Stem Cells from Wistar Rat’s Gingiva (Rattus Novergicus) – Isolation and Characterization (In Vitro Study). J Int Med Res. 2018; 11(2): 694-699.

  • IBL International GMBH. TGF-β 1 ELISA Instructions for use. Hamburg Germany. 2017; 1-11.

  • Emanuele C, Gordon P, Guy C. Regeneration of Acinar Cells following ligation of rat submandibular gland retraces the embryonic-perinatal pathway of cytodifferentiation. International Society of Differentiation. Published by Elsevier Ltd. 2010; 120 -130.

  • Balaji S. Umbilical cord blood as a source of stem cells. Research J. Pharm. and Tech. 2015; 8(8): 1093-1095.

  • Sasikala K. Education to Nursing Students on Collection, Preservation and Utilization of Cord Blood Stem Cells. Asian J. Nur. Edu. and Research. 2011; 1(4):113-116.

  • Selvi ST. Stem Cell Therapy. Int. J. Adv. Nur. Management. 2017; 5(4): 361-364.

  • Patyar DS. Role of Stem Cells in treatment of different Diseases. Research J. Pharm. and Tech 2018; 11(8): 3667-3678.

  • Dauren S, Ahmet D, Kemal K, Mehmet T, Osman A. Local and systemic angiogenic and antiangiogenic response in rats after 70% hepatectomy.. Int J Clin Exp Pathol. 2017; 10(3): 2939-2949.

  • Sakai T. Development and Regeneration of Salivary Gland Toward for Clinical Application. Oral Science International Elseiver. 2016; 13(1): 7-14

  • Li Shiying, Gu Xiasong, Yi Sheng. The Regulatory Effects of Transforming Growth Factor-β on Nerve Regeneration.Cell Transplantation. 2017; 26(3): 381-394

  • Park MS, Kim YH, Jung Y, Kim SH, Park JC, Yoon DS, Kim SH, Park JC, Yoon DS, Kim SH, Lee JW. In situ recruitment of human bone marrow-derived mesenchymal stem cells using chemokines for articular cartilage regeneration. Cell Transplant. 2015; 24(6): 1067

  • Michalopuolos GK. Liver regeneration after partial hepatectomy: critical analysis of mechanistic dilemmas. Am J Pathol. 2010; 176: 2-13.

  • Taniguchi E, Sakisaka S, Matsuo K, Tanikawa K, Sata M. Expression and Role of Vascular Endothelial Growth Factor in liver regeneration after partial hepatectomy in rats. J Histochem Cytochem. 2001; 49: 121-130.

  • Laird DI, Von Andrian UH, Wagers AJ. Stem cell trafficking in tissue development, growth, and disease. Cell. 2008; 132: 612.

  • Maring JA, van Meeteren LA, Goumans MJ, Ten DP. Interrogating TGF-beta function and regulation in endothelial cells. Methods Mol Biol. 2016; 1344: 193.

  • Massague J. TGF-beta signaling in context. Nat Rev Mol Cell Biol. 2012; 13 (10): 616-646.

  • Nakao A, Afrakhte M, Moren A, Nakayama T, Christian JL, Heuchel R, Itoh S, Kawabata M, Heldin NE, Heldin CH, Dijke P. Identification of Smad7, a TGF-ß inducible antagonist of TGF-beta signaling. Nature. 1997; 389 (6651): 631-636.

  • Shiying L, Xiasong G, Sheng Y. The Regulatory Effects of Transforming Growth Factor-β on Nerve Regeneration. Cell Transplantation. 2017; 26: 381-394.

  • Ching-Shwun L, Zhong-Cheng X, Tom FL. Commonly Used Mesenchymal Stem Cell Markers and Tracking Labels: Limitations and Challenges. HHS Public Access. 2013; 28 (9): 1109–1116


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  • The Efficacy of Human Dental Pulp Stem Cells in regenerating Submandibular Gland Defects in Diabetic Wistar Rats (Rattus novergicus)

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Authors

Septiana P. Suciadi
Universitas Airlangga, Surabaya, Indonesia
Alexander P. Nugraha
Orthodontics Department, Universitas Airlangga, Surabaya, Indonesia
Diah S. Ernawati
Oral Medicine Department, Universitas Airlangga, Surabaya, Indonesia
Nurina F. Ayuningtyas
Oral Medicine Department, Universitas Airlangga, Surabaya, Indonesia
Ida B. Narmada
Orthodontics Department, Universitas Airlangga, Surabaya, Indonesia
Chiquita Prahasanti
Periodontics Department, Universitas Airlangga, Surabaya, Indonesia
Aristika Dinaryanti
Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, Indonesia
Igo Syaiful Ihsan
Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, Indonesia
Eryk Hendrinto
Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, Indonesia
Helen Susilowati
Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, Indonesia
Fedik Abdul Rantam
Virology and Immunology Laboratory, Microbiology Department, Universitas Airlangga, Surabaya, Indonesia

Abstract


Chronic hyperglicemia in Diabetes Mellitus caused microangiopathy in salivary gland. Human Dental Pulp Stem Cells (HDPSCs) suspected can regenerate the defect. The aim of this study was to analyze the efficacy of HDPSCs in stimulating angiogenesis, acinar cell numbers and Transforming Growth Factor-β (TGF-β) serum to regenerate submandibular gland defects in diabetic Wistar rats. Twenty-four male Wistar (250-350 g) rats 3-months-old were used. Rats were divided into 4 groups (n=6 each: a positive control group on Day 7 (DM) (C+7), a positive control group on Day 14 (DM) (C+14), a treatment group on Day 7 (DM+5.105 HDPSCs transplantation intraglandular) (T7) and a treatment group on Day 14 (DM+5.105 HDPSCs transplantation intraglandular) (T14). Wistar Rats were administered with 30 mg of Streptozotocin per kg of bodyweight to induce Diabetes Mellitus (DM). Histopathological examination with HE staining was performed to analyse neovascularization and acinar cell numbers. ELISA was performed to measure TGF-β serum. Statistical analysis used: A Tukey HSD or Bonferroni test after ANOVA or Kruskal Wallis test was performed (p<0.05) based on a Saphiro Wilk and Levene’s test (p>0.05). The highest acinar cell number was found in the T7 group [513.167±136.17] with no significant difference [p=0.136, p<0.05]. The highest capillaries were found in T14 [10.667±4.54] and TGF-β serum level [168.87±37.38] with significant difference [p=0.006; p<0.05] and [p=0.008, p<0.05]. HDPSCs can regenerate submandibular gland defects in Diabetic Wistar rats by stimulating angiogenesis, acinar cells number and TGF – β serum.

Keywords


Human Dental Pulp Stem Cells, Submandibular Gland Defect, Diabetes Mellitus, Acinar Cells, Angiogenesis, Transforming Growth Factor-β.

References