Effect of umbilical cord-mesenchymal stem cells on skin tensile strength in pressure ulcers: a rat model study
DOI:
https://doi.org/10.13181/mji.oa.268222Keywords:
elastic modulus, pressure ulcers, rat skin, regenerative medicine, stem cells, tensile strengthAbstract
BACKGROUND Stem cell therapy has emerged as a promising alternative for the management of chronic wounds, including pressure ulcers. Tensile strength, which reflects the biomechanical integrity of the skin, serves as an objective measure of wound healing. This study aimed to evaluate the effect of locally administered umbilical cord-mesenchymal stem cells (UC-MSCs) on the tensile strength of healing 3rd-degree pressure ulcers in a Sprague Dawley rat model.
METHODS 21 adult male Sprague Dawley rats were divided into 3 groups: normal rats without ulcers, untreated pressure ulcer as control, and pressure ulcers treated with UC-MSCs. The treatment group received locally injected 4 × 10⁶ UC-MSCs at the ulcer site. On day-21, the tensile strength parameters (rupture point, elongation at break, and elastic modulus) of the dorsal skin were assessed using the Universal Testing System.
RESULTS When expressed relative to normal skin tensile strength, the UC-MSC group exhibited higher tensile parameters that were higher than the controls by 2.08% for rupture point, 3.29% for elongation at break, and 8.42% for elastic modulus. Although these differences between the UC-MSCs and control groups across all tensile strength parameters were not statistically significant, a clear trend toward improved tensile strength parameters were observed in the UC-MSCs group.
CONCLUSIONS Local UC-MSCs administration showed a consistent trend toward improved tensile strength in healing 3rd-degree pressure ulcers, albeit without statistically significant differences compared to controls. These findings support the further exploration of UC-MSCs as a potential treatment for promoting biomechanical restoration in healing pressure ulcers.
Downloads
References
Leavitt T, Hu M, Marshall C, Barnes L, Longaker M, Lorenz P. Stem cells and chronic wound healing: state of the art. Chronic Wound Care Manag Res. 2016;3:7-27. https://doi.org/10.2147/CWCMR.S84369
Edsberg LE, Black JM, Goldberg M, McNichol L, Moore L, Sieggreen M. Revised National Pressure Ulcer Advisory Panel pressure injury staging system: revised pressure injury staging system. J Wound Ostomy Continence Nurs. 2016;43(6):585-97. https://doi.org/10.1097/WON.0000000000000281
Berdiaki A, Neagu M, Tzanakakis P, Spyridaki I, Pérez S, Nikitovic D. Extracellular matrix components and mechanosensing pathways in health and disease. Biomolecules. 2024;14(9):1186. https://doi.org/10.3390/biom14091186
Loerakker S, Manders E, Strijkers GJ, Nicolay K, Baaijens FP, Bader DL, et al. The effects of deformation, ischemia, and reperfusion on the development of muscle damage during prolonged loading. J Appl Physiol (1985). 2011;111(4):1168-77. https://doi.org/10.1152/japplphysiol.00389.2011
Dejonckheere E, Vandenbroucke RE, Libert C. Matrix metalloproteinases as drug targets in ischemia/reperfusion injury. Drug Discov Today. 2011;16(17-18):762-78. https://doi.org/10.1016/j.drudis.2011.06.009
Schiffman J, Golinko MS, Yan A, Flattau A, Tomic-Canic M, Brem H. Operative debridement of pressure ulcers. World J Surg. 2009;33(7):1396-402. https://doi.org/10.1007/s00268-009-0024-4
Coalson E, Bishop E, Liu W, Feng Y, Spezia M, Liu B, et al. Stem cell therapy for chronic skin wounds in the era of personalized medicine: From bench to bedside. Genes Dis. 2019;6(4):342-58. https://doi.org/10.1016/j.gendis.2019.09.008
Perez-Lopez S, Perez-Basterrechea M, Garcia-Gala JM, Martinez-Revuelta E, Fernandez-Rodriguez A, Alvarez-Viejo M. Stem cell and tissue engineering approaches in pressure ulcer treatment. J Spinal Cord Med. 2023;46(2):194-203. https://doi.org/10.1080/10790268.2021.1916155
Willert JR, Purdon TF, Harris DT. Umbilical cord blood-biology, banking, and therapeutic use. Neonatal Med. 2008;68-72.
Xie Q, Liu R, Jiang J, Peng J, Yang C, Zhang W, et al. What is the impact of human umbilical cord mesenchymal stem cell transplantation on clinical treatment? Stem Cell Res Ther. 2020;11(1):519. https://doi.org/10.1186/s13287-020-02011-z
Huang YZ, Gou M, Da LC, Zhang WQ, Xie HQ. Mesenchymal stem cells for chronic wound healing: current status of preclinical and clinical studies. Tissue Eng Part B Rev. 2020;26(6):555-70. https://doi.org/10.1089/ten.teb.2019.0351
Griffin MF, Leung BC, Premakumar Y, Szarko M, Butler PE. Comparison of the mechanical properties of different skin sites for auricular and nasal reconstruction. J Otolaryngol Head Neck Surg. 2017;46(1):33. https://doi.org/10.1186/s40463-017-0210-6
Bellare A, Epperly MW, Greenberger JS, Fisher R, Glowacki J. Development of tensile strength methodology for murine skin wound healing. MethodsX. 2018;5:337-44. https://doi.org/10.1016/j.mex.2018.04.002
Živčák J, Hudák R, Tóth T. Rat skin wounds tensile strength measurements in the process of healing. In: 2012 IEEE 10th International Symposium on Applied Machine Intelligence and Informatics (SAMI) [Internet]. Herl'any: IEEE; 2012 [cited 2024 Apr 27]. p. 389-92. Available from: http://ieeexplore.ieee.org/document/6208996/. https://doi.org/10.1109/SAMI.2012.6208996
Arifin WN, Zahiruddin WM. Sample size calculation in animal studies using resource equation approach. Malays J Med Sci. 2017;24(5):101-5. https://doi.org/10.21315/mjms2017.24.5.11
Institutional Animal Care and Use Committee. IACUC guidelines: anesthesia [Internet]. Iowa: University of Iowa; 2023 [cited 2024 Aug 3]. Available from: https://animal.research.uiowa.edu/iacuc-guidelines-anesthesia.
Stadler I, Zhang RY, Oskoui P, Whittaker MS, Lanzafame RJ. Development of a simple, noninvasive, clinically relevant model of pressure ulcers in the mouse. J Invest Surg. 2004;17(4):221-7. https://doi.org/10.1080/08941930490472046
de la Garza-Rodea AS, Knaän-Shanzer S, van Bekkum DW. Pressure ulcers: description of a new model and use of mesenchymal stem cells for repair. Dermatology. 2011;223(3):266-84. https://doi.org/10.1159/000334628
Pawitan JA, Kispa T, Mediana D, Goei N, Fasha I, Liem IK, et al. Simple production method of umbilical cord derived mesenchymal stem cell using xeno-free materials for translational research. J Chem Pharm Res. 2015;7(8):652-6.
Mediana D, Liem IK, Pawitan JA, Goei N. Passage effect on aging of human umbilical cord derived mesenchymal stem cell. Online J Biol Sci. 2015;15(3):170-7. https://doi.org/10.3844/ojbsci.2015.170.177
American Veterinary Medical Association (AVMA). AVMA guidelines for the euthanasia of animals: 2020 edition. Schaumburg: American Veterinary Medical Association; 2020.
van de Vyver M, Boodhoo K, Frazier T, Hamel K, Kopcewicz M, Levi B, et al. Histology scoring system for murine cutaneous wounds. Stem Cells Dev. 2021;30(23):1141-52. https://doi.org/10.1089/scd.2021.0124
Aziz J, Shezali H, Radzi Z, Yahya NA, Abu Kassim NH, Czernuszka J, et al. Molecular mechanisms of stress-responsive changes in collagen and elastin networks in skin. Skin Pharmacol Physiol. 2016;29(4):190-203. https://doi.org/10.1159/000447017
Farabi B, Roster K, Hirani R, Tepper K, Atak MF, Safai B. The efficacy of stem cells in wound healing: a systematic review. Int J Mol Sci. 2024;25(5):3006. https://doi.org/10.3390/ijms25053006
Raghuram AC, Yu RP, Lo AY, Sung CJ, Bircan M, Thompson HJ, et al. Role of stem cell therapies in treating chronic wounds: a systematic review. World J Stem Cells. 2020;12(7):659-75. https://doi.org/10.4252/wjsc.v12.i7.659
Tan ST, Aisyah PB, Firmansyah Y, Nathasia N, Budi E, Hendrawan S. Effectiveness of secretome from human umbilical cord mesenchymal stem cells in gel (10% SM-hUCMSC Gel) for chronic wounds (diabetic and trophic ulcer) - phase 2 clinical trial. J Multidiscip Healthc. 2023;16:1763-77. https://doi.org/10.2147/JMDH.S408162
Caplan AI. MSCs: the sentinel and safe-guards of injury. J Cell Physiol. 2016;231(7):1413-6. https://doi.org/10.1002/jcp.25255
Liu L, Yu Y, Hou Y, Chai J, Duan H, Chu W, et al. Human umbilical cord mesenchymal stem cells transplantation promotes cutaneous wound healing of severe burned rats. PLoS One. 2014;9(2):e88348. https://doi.org/10.1371/journal.pone.0088348
Liu Z, Yu D, Xu J, Li X, Wang X, He Z, et al. Human umbilical cord mesenchymal stem cells improve irradiation-induced skin ulcers healing of rat models. Biomed Pharmacother. 2018;101:729-36. https://doi.org/10.1016/j.biopha.2018.02.093
Jin Y, Meng M, Zhang Y, Mo L, Gao H, Liu Y, et al. Comparative study on the efficacy of PRP gel and UC-MSCs gel as adjuvant therapies in the treatment of DFU wounds. Skin Res Technol. 2024;30(1):e13549. https://doi.org/10.1111/srt.13549
Sun Y, Zhu M, Qiu L. Efficacy of mesenchymal stem cells and platelet-rich plasma therapies on wound healing: a systematic review and meta-analysis. Regen Ther. 2025;30:75-91. https://doi.org/10.1016/j.reth.2025.04.010
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Indri Aulia, Ismail Hadisoebroto Dilogo, Theddeus Octavianus Hari Prasetyono, Jeanne Adiwinata Pawitan, Aria Kekalih, Nurjati Chairani Siregar, Yudan Whulanza, Lisa Hasibuan

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with Medical Journal of Indonesia agree to the following terms:
- Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
- Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.



