The effect of mesenchymal stem cells derived from different sources on diabetic wound healing
Abstract
Purpose: It is unclear whether the tissue source of mesenchymal stem cells (MSCs) influences their activity in diabetic wounds. This study aimed to compare the effects of dental pulp–derived and adipose tissue–derived MSCs on wound healing and on the cutaneous expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, and IL-10 in streptozotocin (STZ)-induced diabetic rats.
To compare the effects of dental pulp–derived and adipose tissue–derived MSCs on diabetic wound healing and on the cutaneous expression of TNF-α, IL-1, IL-6, and IL-10 in a streptozotocin (STZ)-induced diabetic rat model.
Materials and methods: Twenty-four male rats were allocated to four groups (n=6 each): non-diabetic control, diabetic control, and diabetic wounds treated with dental pulp–derived or adipose tissue–derived MSCs. Diabetes was induced with STZ (55 mg/kg, intraperitoneally). A 5 mm full-thickness wound was created, and 1×10⁶ MSCs were applied topically in the treatment groups. On day 10, skin sections were evaluated by hematoxylin–eosin and Masson's trichrome staining, and cytokine expression was scored immunohistochemically using the H-score.
Results: Wound diameter did not differ significantly between the non-diabetic control and the MSC-treated groups, whereas the diabetic control showed significantly larger wounds. Histologically, both MSC-treated groups showed a thicker, better-organized epidermis and denser dermal collagen than the diabetic control. Compared with the diabetic control, both MSC-treated groups showed significantly lower IL-1 and IL-6 expression and higher IL-10 expression, whereas TNF-α expression did not change significantly. No significant differences were observed between the dental pulp– and adipose tissue–derived MSC groups for any marker except IL-10, which was higher in the adipose tissue–derived MSC group.
Conclusion: Topical application of dental pulp– or adipose tissue–derived MSCs supported diabetic wound healing through an anti-inflammatory shift characterized by lower IL-1 and IL-6 and higher IL-10 expression, without significantly affecting TNF-α.
Keywords
Mesenchymal stem cells, diabetes mellitus, wound healing, immunohistochemistry
References
- 1. Han, G., & Ceilley, R. (2017). Chronic wound healing: A review of current management and treatments. Advances in Therapy, 34(3), 599-610. https://doi.org/10.1007/s12325-017-0478-y
- 2. Rodrigues, M., Kosaric, N., Bonham, C. A., & Gurtner, G. C. (2019). Wound healing: A cellular perspective. Physiological Reviews, 99(1), 665-706. https://doi.org/10.1152/physrev.00067.2017
- 3. American Diabetes Association. (2014). Diagnosis and classification of diabetes mellitus. Diabetes Care, 37(Suppl 1), S81–S90. https://doi.org/10.2337/dc14-S081
- 4. Armstrong, D. G., Tan, T. W., Boulton, A. J. M., & Bus, S. A. (2023). Diabetic foot ulcers: A review. JAMA, 330(1), 62–75. https://doi.org/10.1001/jama.2023.10578
- 5. Guo, S., & DiPietro, L. A. (2010). Factors affecting wound healing. Journal of Dental Research, 89(3), 219–229. https://doi.org/10.1177/0022034509359125
- 6. Wilkinson, H. N., & Hardman, M. J. (2020). Wound healing: Cellular mechanisms and pathological outcomes. Open Biology, 10(9), Article 200223. https://doi.org/10.1098/rsob.200223
- 7. Ladley, S. M., & Naghdi, S. (2026). The use of adipose-derived stem cells in chronic wound healing. International Wound Journal, 23(7), Article e70986. https://doi.org/10.1111/iwj.70986
- 8. Yu, X., Liu, P., Li, Z., & Zhang, Z. (2023). Function and mechanism of mesenchymal stem cells in the healing of diabetic foot wounds. Frontiers in endocrinology, 14, 1099310. https://doi.org/10.3389/fendo.2023.1099310
- 9. Milan, M., Takla, J., Hayek, F., Emmanuel, N., Nicolas, G., & Menendez, J. P. (2024). Regenerative potential of adipose-derived stem cells in wound healing and scar management: A review. Current Dermatology Reports, 13, 351–360. https://doi.org/10.1007/s13671-024-00442-y
- 10. Liu, Y., Liu, Y., Wu, M., Zou, R., Mao, S., Cong, P., Hou, M., Jin, H., Zhao, Y., & Bao, Y. (2022). Adipose-derived mesenchymal stem cell-loaded β-chitin nanofiber hydrogel promotes wound healing in rats. Journal of Materials Science: Materials in Medicine, 33(2), Article 12. https://doi.org/10.1007/s10856-021-06630-7
