Medical Radiology and Radiation Safety. 2024. Vol. 69. № 3

DOI:10.33266/1024-6177-2024-69-3-5-12

A.A. Rastorgueva1, T.A. Astrelina1, V.A. Brunchukov1, I.V. Kobzeva1,
Yu.B. Suchkova1, V.A. Nikitina1, S.V. Lishchuk1, E.A. Dubova1, K.A. Pavlov1,
T.F. Malivanova1, D.Yu. Usupzhanova1, O.G. Mikhadarkina1, A.D. Kobzev2,
V.I. Bulygina2, A.S. Samoilov1

Evaluation of the Effectiveness of The Use of Decellularized Human Amniotic Membrane
in Combination with Cell Therapy for Local Radiation Injuries

1 A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia

2 M.I. Sechenov University, Moscow, Russia

Contact person: T.A. Astrelina, e-mail: Этот адрес электронной почты защищен от спам-ботов. У вас должен быть включен JavaScript для просмотра.

 

Аbstract

Cell therapy is a promising direction in medicine, which can significantly improve the results of treatment of various diseases, including local radiation injuries (LRI). The purpose of the study was to compare the results of using decellularized human amniotic membrane isolated and together with lyophilisates of conditioned media of MSCs from the human gingival mucosa and MSCs from human placental tissue and their effect on tissue regeneration in LRI. 

Material and methods: The study included 42 laboratory animals (white male rats of the Wistar line), randomly divided into 6 groups: K – control group without therapy, on the 21st day after irradiation, groups using: Am+LD – application of lyophilisate of the conditioned medium of MSCs of the human gingival mucosa (LD) under the decellularized amniotic membrane, Am+LP – application of lyophilisate of the conditioned medium of MSCs of human placental tissue (LP) under the decellularized amniotic membrane, Am – application of the decellularized amniotic membrane, AmCl – application of the decellularized amniotic membrane with medical glue BF-6, Kl – application medical glue BF-6. Modeling of LRI in animals was carried out on an LNK-268 X-ray unit at a dose of 110 Gy and observed until the 112th day after irradiation, monitoring of the ulcerative surface of the skin and the course of the inflammatory process of LRI was carried out with calculation of the area of ​​the total changed skin in the ImageTool software. Planimetric and histological analyzes were performed. 

Results: It was demonstrated that, when compared with the control, the use of decellularized amniotic membrane in LRI on days 77 and 112 after irradiation increased the healing rate by 4.6 and 18 times, respectively; decellularized amniotic membrane with lyophilisate of placental MSC conditioned medium increased the rate of wound healing by 13.5 and 27 times, respectively; and a dellularized amniotic membrane with lyophilisate of MSCs from the human gingival mucosa to 100 % healing. Healing of the ulcer surface area of the LRI in 83.5 % of animals in the Am group demonstrated the effectiveness of using isolated decellularized amniotic membrane even in the absence of human MSC lyophilisates. At the same time, healing of the ulcer surface area of the LRI in the AmCl group was 20 % of cases, where the decellularized amniotic membrane was fixed with BF-6 medical glue, which was less effective compared
to other groups.

Conclusion: The proposed combined use of decellularized amniotic membrane with lyophilisates of the conditioned medium of mesenchymal stromal cells (MSCs) of the placenta and mucous tissue of the human gums and the isolated use of decellularized amniotic membrane led to complete epithelization of the ulcer surface, a pronounced favorable course of grade IIIb–IV LRI in laboratory animals and a reduction in healing time , the absence of local or systemic complications can be considered as a promising method of conservative treatment for LRI of the skin and a new therapeutic approach in the treatment of non-healing and chronic wounds.

Keywords: local radiation injuries, human decellularized amniotic membrane, cell therapy, mesenchymal stromal cells, conditioned medium, rats

For citation: Rastorgueva AA, Astrelina TA, Brunchukov VA, Kobzeva IV, Suchkova YuB, Nikitina VA, Lishchuk SV, Dubova EA, Pavlov KA, Malivanova TF, Usupzhanova DYu, Mikhadarkina OG, Kobzev AD, Bulygina VI, Samoilov AS. Evaluation of the Effectiveness of The Use of Decellularized Human Amniotic Membrane in Combination with Cell Therapy for Local Radiation Injuries. Medical Radiology and Radiation Safety. 2024;69(3):5–12. (In Russian). DOI:10.33266/1024-6177-2024-69-3-5-12 

 

References

1. Diagnosis, Treatment of Local Radiation Injuries and Their Long-Term Consequences. Federal Clinical Guidelines. FKR FMBA of Russia 2.6.7. Moscow, 2015.

2. Brunchukov V.A., Astrelina T.A., Nikitina V.A., et al. The Use of Placental Mesenchymal Stromal Cells for Local Radiation Lesions of the Skin. Genes and Cells. 2019;14:41 (In Russ.).

3. Rastorgueva A.A., Astrelina T.A., Brunchukov V.A., et al. The Effectiveness of the Use of Rat and Human MSCs and Their Conditioned Media for Local Radiation Injuries in a Laboratory Animal Model. Genes and cells. 2022;3;17:194 (In Russ.).

4. Brunchukov V., Astrelina T., Nikitina V., et al. Experimental Treatment of Radiation Skin Lesions with Mesenchymal Stem Cells and Their Conditioned Media. Medical Radiology and Radiation Safety. 2020;65;1:5-12. doi:10.12737/1024-6177-2020-65-1-5-12. 

5. Rastorgueva A.A., Astrelina T.A., Brunchukov V.A., et al. Application of Cellular Technologies in the Treatment of Local Radiation Injuries. Abstract book IRPA15. 15 th International Congress of the International Radiation Protection Association. January 18-22, 2021 in Seoul, Korea. Korea, Р. 328-333. 

6. Kobzeva I.V., Astrelina T.A., Brunchukov V.A., et al. Transplantation of Decellularized Human Amniotic Membrane for Local Radiation Injuries. Medical Radiology and Radiation Safety. 2022;67;6:5-11 (In Russ.).

7. Chen P., Lu M., Wang T., et al. Human Amniotic Membrane as a Delivery Vehicle for Stem Cell-Based Therapies. Life Sci. 2021;1;272:119157. doi: 10.1016/j.lfs.2021.119157.

8. Leal-Marin S., Kern T., Hofmann N., et al. Human Amniotic Membrane: A Review on Tissue Engineering, Application, and Storage. J. Biomed Mater Res. B. Appl. Biomater. 2021;109;8:1198-1215. doi: 10.1002/jbm.b.34782.

9. Panteleyev A.A., Sytina E.V., Chaban E.A., Paltsev M.A. Use of Human Fetal Amniotic Membrane in Skin Bioengineering. Molecular Medicine. 2016;14;5:49-54 (In Russ.).

10. Jahanafrooz Z., Bakhshandeh B., Behnam Abdollahi S., et al. Human Amniotic Membrane as a Multifunctional Biomaterial: Recent Advances and Applications // J. Biomater Appl. 2023. V.37. No. 8. P. 1341-1354. doi: 10.1177/08853282221137609.

11. Samoilov A.S., Astrelina T.A., Brumberg V.A., Brunchukov V.A., Kobzeva I.V., Malivanova T.F., Ostashkin A.S. A Method for Obtaining an Acellular Matrix of the Amniotic Membrane for Subsequent Reconstruction of Tissue Defects. Patent for Invention No. 2751353RU dated 07/13/2021] (In Russ.).

12. Kakabadze Z., Chakhunashvili D., Gogilashvili K., Ediberidze K., Chakhunashvili K., Kalandarishvili K., Karalashvili L. Bone Marrow Stem Cell and Decellularized Human Amniotic Membrane for the Treatment of Nonhealing Wound after Radiation Therapy. Exp. Clin. Transplant. 2019;17;1:92-98. doi: 10.6002/ect.MESOT2018.O29.

13. Asanuma H., Meldrum D.R., Meldrum K.K. Therapeutic Applications of Mesenchymal Stem Cells to Repair Kidney Injury. J. Urol. 2010;184;1:26-33.

14. Walter M.N., Wright K.T., Fuller H.R., MacNeil S., Johnson W.E. Mesenchymal Stem Cell-Conditioned Medium Accelerates Skin Wound Healing: an in Vitro Study of Fibroblast and Keratinocyte Scratch Assays. Exp. Cell. Res. 2010;316;7:1271-1281.

15. Kwon H.M., Hur S.M., Park K.Y., et al. Multiple Paracrine Factors Secreted by Mesenchymal Stem Cells Contribute to Angiogenesis. Vascul. Pharmacol. 2014;63;1:19-28.

16. Koob T.J., Lim J.J., Massee M., Zabek N., Denoziere G. Properties of Dehydrated Human Amnion/Chorion Composite Grafts: Implications for Wound Repair and Soft Tissue Regeneration. J. Biomed Mater Res. B Appl. Biomater. 2014;102;6:1353-1362.

17. Guo Q., Lu X., Xue Y., et al. A New Candidate Substrate for Cell-Matrix Adhesion Study: the Acellular Human Amniotic Matrix. J. Biomed Biotechnol. 2012;2012:306083.

18. Mrugala A., Sui A., Plummer M., et al. Amniotic Membrane Is a Potential Regenerative Option for Chronic Non-Healing Wounds: a Report of Five Cases Receiving Dehydrated Human Amnion/Chorion Membrane Allograft. Int. Wound J. 2016;13;4:485-492.

 

 

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Conflict of interest. The authors declare no conflict of interest.

Financing. The study was carried out with financial support from the Federal Target Program “Ensuring Nuclear and Radiation Safety for 2016–2020 and for the period until 2035”.

Contribution. Article was prepared with equal participation of the authors.

Article received: 20.01.2024. Accepted for publication: 27.02.2024.