Efficacy of the human recombinant angiogenin in CD-1 mice skin burn wound therapy

Both the skin's own cellular components and physiologically active substances, such as cytokines, actively participate in the protracted and intricate process of skin burn wound healing. One of these molecules is angiogenin, a ribonuclease that encourages the development of a vascular network where tissue and organ damage has occurred. The study compared the effects of intradermal delivery of human skin fibroblast cells, EA.Hy926 endothelial cells, conditioned media from human bone marrow mesenchymal stem cells, and human recombinant angiogenin after thermal skin burn in female CD-1 mice.

Material and methods. Using a metal plate heated to 200–250 °C over the flame, a thermal skin burn in the back area was initiated. Treatment was started immediately after the initiation of the burn wound. Recombinant human angiogenin (1 ml of solution containing 10 μg of active agent) was administered once, twice, and three times with an interval of 7 days; conditioned media from human somatic cells (1 ml) were administered once. A caliper was used to measure the size of the wound on days 7, 14, and 21. Blood and a piece of skin from the burn wound were collected when the animals were removed from the experiment. Using spectrophotometry, the amounts of NO and cytokines (IL-1β, TNFα, IL-10, and VEGF) in blood serum and extract of skin samples were measured. The squamous epithelium, granulation tissue, blood vessel count, lymphocytes, neutrophils, macrophages, plasmocytes, and fibroblasts were all evaluated by histological analysis of skin samples.

Results and discussion. Human recombinant angiogenin or conditioned media derived from human somatic cells significantly accelerated the repair of wound skin defects in groups of mice with thermal burns. A conditioned media derived from human bone marrow mesenchymal stem cells is as effective as a single injection of human recombinant angiogenin. The wound defect's epithelialization, granulation tissue development, and increased angiogenesis were all facilitated by treatment with human recombinant angiogenin and conditioned media derived from human somatic cells. It has been demonstrated that variations in cytokine and NO levels in blood serum and skin occur depending on the type of treatment and the length of observation. The morphometric characteristics of skin samples taken from the burn site were found to correlate with these parameters.

Conclusions. Injections of the biomedical cell product into the area of thermal skin burns in female CD-1 mice accelerate wound defect healing.

1. Markiewicz-Gospodarek A., Kozioł M., Tobiasz M., Baj J., Radzikowska-Büchner E., Przekora A. Burn wound healing: clinical complications, cedical care, treatment, and dressing types: the current state of knowledge for clinical practice. Int. J. Environ. Res. Public Health. 2022;19(3):1338. doi: 10.3390/ijerph19031338

2. Ullah S., Mansoor S., Ayub A., Ejaz M., Zafar H., Feroz F., Khan A., Ali M. An update on stem cells applications in burn wound healing. Tissue Cell. 2021;72:101527. doi: 10.1016/j.tice.2021.101527

3. Zheng W., Zhao D.L., Zhao Y.Q., Li Z.Y. Effectiveness of platelet rich plasma in burn wound healing: a systematic review and meta-analysis. J. Dermatolog. Treat. 2022:33(1):131–137. doi: 10.1080/09546634.2020.1729949

4. Singh K., Maity P., Koroma A.K., Basu A., Pandey R.K., Vander Beken S., Haas P., Krug L., Hainzl A., Sindrilaru A., … Scharffetter-Kochanek K. Angiogenin released from ABCB5+stromal precursors improves healing of diabetic wounds by promoting angiogenesis. J. Invest. Dermatol. 2022:142(6):1725–1736.e10. doi: 10.1016/j.jid.2021.10.026

5. Shpichka A., Butnaru D., Bezrukov E.A., Sukhanov R.B., Atala A., Burdukovskii V., Zhang Y., Timashev P. Skin tissue regeneration for burn injury. Stem Cell Res. Ther. 2019:10(1): 94. doi: 10.1186/s13287-019-1203-3

6. Kim J.H., Green D.S., Ju Y.M., Harrison M., Vaughan J.W., Atala A., Lee S.J., Jackson J.D., Nykiforuk C., Yoo J.J. Identification and characterization of stem cell secretome-based recombinant proteins for wound healing applications. Front. Bioeng. Biotechnol. 2022;10:954682. doi: 10.3389/fbioe.2022.954682

7. Subramaniam T., Shaiful Hadi N., Sulaiman S., Fauzi M.B., Hj Idrus R.B., Chowdhury S.R., Law J.X., Maarof M. Comparison of three different skin substitutes in promoting wound healing in an ovine model. Burns. 2022;48(5):1198–1208. doi: 10.1016/j.burns.2021.08.012

8. Pan S.C., Lee C.H., Chen C.L., Fang W.Y., Wu L.W. Angiogenin attenuates scar formation in burn patients by reducing fibroblast proliferation and transforming growth factor β1 secretion. Ann. Plast. Surg. 2018;80(2S, Suppl. 1):S79–S83. doi: 10.1097/SAP.0000000000001306