Subscribe to RSS

DOI: 10.1055/s-0044-1791940
Evaluation of Regeneration Potential of Bone Marrow–Derived Mesenchymal Stem Cells on Induced Damaged Submandibular Salivary Gland in Mice

Abstract
Objectives The ultimate goal of stem cell (SC) transplantation is the regeneration of salivary gland function by transplanted SCs differentiating into salivary gland cells. Therefore, this study aimed to evaluate the regenerative capacity of bone marrow–derived mesenchymal stem cells (BM-MSCs) transplantation in irradiated mice using the immunohistochemical markers Ki-67 and CD34.
Material and Methods Four groups of male mice were included in the study. Group I (normal control) comprised six mice that were not subjected to gamma radiation. Group II comprised six irradiated mice that were not treated with BM-MSCs. Group III comprised 12 irradiated mice that were treated with intraglandular injection of labeled BM-MSCs into their submandibular salivary glands, 24 hours postradiation. Group IV comprised 12 irradiated mice that were treated with intraglandular injection of labeled BM-MSCs into their submandibular salivary glands, on day 11 postradiation.
Statistical Analysis Data were presented as mean and standard deviation. The different groups were compared using a one-way analysis of variance (ANOVA).
Results The ANOVA test revealed that the difference between all groups was extremely statistically significant (p < 0.003), and Tukey's post hoc test revealed a statistically significant difference between group II and groups I, III, and IV included in the study regarding microvessel density of CD34 immunoexpression in different groups.
Conclusion BM-MSCs have a regeneration potential on induced damaged submandibular salivary glands in mice; time is an essential factor in the regeneration capacity of BM-MSCs.
Note
This work was performed at the Faculty of Dental Medicine for Girls, Al Azhar University, Cairo, Egypt.
Publication History
Article published online:
12 March 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
-
References
- 1 Pultrone L, Schmid R, Waltimo T, Braissant O, Astasov-Frauenhoffer M. Saliva profiling with differential scanning calorimetry: a feasibility study with ex vivo samples. PLoS One 2022; 17 (06) e0269600
- 2 Pillai S, Munguia-Lopez JG, Tran SD. Hydrogels for salivary gland tissue engineering. Gels 2022; 8 (11) 730
- 3 Barrows CML, Wu D, Farach-Carson MC, Young S. Building a functional salivary gland for cell-based therapy: more than secretory epithelial acini. Tissue Eng Part A 2020; 26 (23–24): 1332-1348
- 4 Buranarom N, Komin O, Matangkasombut O. Hyposalivation, oral health, and Candida colonization in independent dentate elders. PLoS One 2020; 15 (11) e0242832
- 5 Tanaka J, Mishima K. Application of regenerative medicine to salivary gland hypofunction. Jpn Dent Sci Rev 2021; 57: 54-59
- 6 Hoang DM, Pham PT, Bach TQ. et al. Stem cell-based therapy for human diseases. Signal Transduct Target Ther 2022; 7 (01) 272
- 7 Merimi M, El-Majzoub R, Lagneaux L. et al. The therapeutic potential of mesenchymal stromal cells for regenerative medicine: current knowledge and future understandings. Front Cell Dev Biol 2021; 9: 661532
- 8 Jin Y, Li S, Yu Q, Chen T, Liu D. Application of stem cells in regeneration medicine. MedComm 2023; 4 (04) e291
- 9 Guan Z, Zhang J, Jiang N, Tian M, Wang H, Liang B. Efficacy of mesenchymal stem cell therapy in rodent models of radiation-induced xerostomia and oral mucositis: a systematic review. Stem Cell Res Ther 2023; 14 (01) 82
- 10 Kamala KA, Kanetkar SR, Datkhile KD, Sankethguddad S. Expression of Ki67 biomarker in oral submucous fibrosis with clinico-pathological correlations: a prospective study. Asian Pac J Cancer Prev 2022; 23 (01) 253-259
- 11 Mansy M, Soliman M, Mubarak R, Shamel M. The role of exogenous epidermal growth factor on Ki-67 proliferation marker expression in the submandibular salivary gland of albino rats receiving doxorubicin. F1000 Res 2020; 9: 1393
- 12 Radu P, Zurzu M, Paic V. et al. CD34-structure, functions and relationship with cancer stem cells. Medicina (Kaunas) 2023; 59 (05) 938
- 13 Hassanpour M, Salybekov AA, Kobayashi S, Asahara T. CD34 positive cells as endothelial progenitor cells in biology and medicine. Front Cell Dev Biol 2023; 11: 1128134
- 14 Snykers S, Vanhaecke T, Rogiers V. Isolation of rat bone marrow stem cells. Methods Mol Biol 2006; 320: 265-272
- 15 Dvorakova J, Hruba A, Velebny V, Kubala L. Isolation and characterization of mesenchymal stem cell population entrapped in bone marrow collection sets. Cell Biol Int 2008; 32 (09) 1116-1125
- 16 Mizrachi A, Cotrim AP, Katabi N, Mitchell JB, Verheij M, Haimovitz-Friedman A. Radiation-induced microvascular injury as a mechanism of salivary gland hypofunction and potential target for radioprotectors. Radiat Res 2016; 186 (02) 189-195
- 17 Krishnan M, Tennavan A, Saraswathy S, Sekhri T, Singh AK, Nair V. Acute radiation-induced changes in Sprague-Dawley rat submandibular glands: a histomorphometric analysis. World J Oncol 2017; 8 (02) 45-52
- 18 Lim JY, Yi T, Choi JS. et al. Intraglandular transplantation of bone marrow-derived clonal mesenchymal stem cells for amelioration of post-irradiation salivary gland damage. Oral Oncol 2013; 49 (02) 136-143
- 19 Soleimanpour H, Shirian S, Oryan A, Daneshbod K, Bagheri N, Daneshbod Y. Cytologic, immunocytologic, histopathologic and immunohistologic diagnosis of the poorly differentiated Sertoli-Leydig cell tumor. Acta Cytol 2011; 55 (04) 382-386
- 20 Vistoso Monreal A, Polonsky G, Shiboski C, Sankar V, Villa A. Salivary gland dysfunction secondary to cancer treatment. Front Oral Health 2022; 3: 907778
- 21 Jasmer KJ, Gilman KE, Muñoz Forti K, Weisman GA, Limesand KH. Radiation-induced salivary gland dysfunction: mechanisms, therapeutics and future directions. J Clin Med 2020; 9 (12) 4095
- 22 Zhang J, Cui L, Xu M, Zheng Y. Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice. PLoS One 2014; 9 (11) e113721
- 23 Liu Z, Dong L, Zheng Z. et al. Mechanism, prevention, and treatment of radiation-induced salivary gland injury related to oxidative stress. Antioxidants 2021; 10 (11) 1666
- 24 Jensen SB, Vissink A, Limesand KH, Reyland ME. Salivary gland hypofunction and xerostomia in head and neck radiation patients. J Natl Cancer Inst Monogr 2019; 2019 (53) lgz016
- 25 Peng X, Wu Y, Brouwer U. et al. Cellular senescence contributes to radiation-induced hyposalivation by affecting the stem/progenitor cell niche. Cell Death Dis 2020; 11 (10) 854
- 26 Rocha PHP, Reali RM, Decnop M. et al. Adverse radiation therapy effects in the treatment of head and neck tumors. Radiographics 2022; 42 (03) 806-821
- 27 Yu Z, Xu C, Song B. et al. Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances. J Transl Med 2023; 21 (01) 708
- 28 Barazzuol L, Coppes RP, van Luijk P. Prevention and treatment of radiotherapy-induced side effects. Mol Oncol 2020; 14 (07) 1538-1554
- 29 Altrieth AL, O'Keefe KJ, Gellatly VA. et al. Identifying fibrogenic cells following salivary gland obstructive injury. Front Cell Dev Biol 2023; 11: 1190386
- 30 Zheng D, Liu J, Piao H, Zhu Z, Wei R, Liu K. ROS-triggered endothelial cell death mechanisms: focus on pyroptosis, parthanatos, and ferroptosis. Front Immunol 2022; 13: 1039241
- 31 Rezvani M. Therapeutic potential of mesenchymal stromal cells and extracellular vesicles in the treatment of radiation lesions: a review. Cells 2021; 10 (02) 427
- 32 Park YJ, Koh J, Gauna AE, Chen S, Cha S. Identification of regulatory factors for mesenchymal stem cell-derived salivary epithelial cells in a co-culture system. PLoS One 2014; 9 (11) e112158
- 33 Wang W, Lei W, Jiang L. et al. Therapeutic mechanisms of mesenchymal stem cells in acute respiratory distress syndrome reveal potentials for Covid-19 treatment. J Transl Med 2021; 19 (01) 198
- 34 Planat-Benard V, Varin A, Casteilla L. MSCs and inflammatory cells crosstalk in regenerative medicine: concerted actions for optimized resolution driven by energy metabolism. Front Immunol 2021; 12: 626755
- 35 Helissey C, Cavallero S, Guitard N, Théry H, Chargari C, François S. Revolutionizing radiotoxicity management with mesenchymal stem cells and their derivatives: a focus on radiation-induced cystitis. Int J Mol Sci 2023; 24 (10) 9068
- 36 Najafi S, Nosrati H, Faraji Z. et al. Reconstruction of necrotic submandibular salivary gland using mesenchymal stem cells. Heliyon 2020; 6 (10) e05162
- 37 Jomova K, Raptova R, Alomar SY. et al. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol 2023; 97 (10) 2499-2574
- 38 Wijerathne H, Langston JC, Yang Q. et al. Mechanisms of radiation-induced endothelium damage: emerging models and technologies. Radiother Oncol 2021; 158: 21-32
- 39 Mulyani SWM, Astuti ER, Wahyuni OR, Ernawati DS, Ramadhani NF. Xerostomia therapy due to ionized radiation using preconditioned bone marrow-derived mesenchymal stem cells. Eur J Dent 2019; 13 (02) 238-242
- 40 Park KS, Bandeira E, Shelke GV, Lässer C, Lötvall J. Enhancement of therapeutic potential of mesenchymal stem cell-derived extracellular vesicles. Stem Cell Res Ther 2019; 10 (01) 288