Comparison of the Therapeutic Potential of Rat and Human Mesenchymal Stromal Cells and Their Conditioned Media in Local Radiation Lesions
Abstract and keywords
Abstract (English):
Background: To compare the results of the use of mesenchymal stromal cells (MSCs) of human gingival mucosa and MSCs of rat gingival mucosa, their conditioned media, and to evaluate their effect on tissue regeneration in local radiation injury (LRI). Material and methods: The study included 120 white male Wistar rats weighing 210 ± 30 g at the age of 8–12 weeks, randomized into 6 groups (20 animals each): control (C), animals did not receive therapy; control with the introduction of culture medium concentrate (CM) three times for 1, 14, 21 days; administration of human gingival mucosa MSCs (HM) at a dose of 2 million per 1 kg three times for 1, 14, 21 days; administration of human gingival mucosa MSCS conditioned medium concentrate (HMCM) at a calculated dose of 2 million cells per 1 kg three times for 1, 14, 21 days; administration of rat gingival mucosal MSCs (RM) at a dose of 2 million cells per 1 kg three times for 1, 14, 21 days; administration of rat gingival mucosal MSCS (RMCM) conditioned medium concentrate at a calculated dose of 2 million cells per 1 kg three times for 1, 14, 21 days. Each laboratory animal was observed 17 times: on 1, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91, 98, 105, 112 day after the burn simulation. Histological (hematoxylin-eosin staining) and immunohistochemical (CD31, CD68, VEGF, PGP 9.5, MMP2,9, Collag 1, TIMP 2) studies were performed. LRI was modeled on an X-ray machine at a dose of 110 Gy. MSCs were cultured according to the standard method up to 3–5 passages, the conditioned medium was taken and concentrated 10 times. The immunophenotype of MSCs (CD34, CD45, CD90, CD105, CD73, HLA-DR) and viability (7‑ADD) were determined by flow cytofluorimetry. Results: In a comparative analysis with the control group (C), starting from the 42nd day of the study, a tendency to reduce the area of skin ulcers in animals in all groups was observed, despite the fact that not all days had statistically significant differences. On day 112th, complete healing of skin ulcers in the CM group was observed in 40 % of animals in the HM group – in 60 %, in the HMCM group – in 20 % of animals, in the RMCM group–20 %, and in the C and RM groups there were no animals with a prolonged wound defect. Positive expression of the VEGF marker was observed in groups C and CM on the 28th day and in experimental groups (HM, HMCM, RM, RMCM) on the 112th day. A statistically significant increase in the CD68 marker was observed in groups C, RM, and RMCM, while the remaining groups showed a decrease in the number of macrophages.

Keywords:
mesenchymal stromal cells, local radiation lesions, conditioned medium, cell technologies, X-ray radiation, skin
References

1. Brunchukov V.A. , Astrelina T.A., Nikitina V.A., Kobzeva I.V., Suchkova Yu.B., Usupzhanova D.Yu., i dr. Primenenie mezenhimal'nyh stromal'nyh kletok placenty pri mestnyh luchevyh porazheniyah kozhi. Geny i kletki. 2019, T. 14, Prilozhenie 41 s.

2. Eremin P.S., Deev R.V., Bozo I.Ya., Deshevoy Yu.B., Lebedev V.G., Eremin I.I., i dr. Zazhivlenie tkaney v oblasti tyazhelogo mestnogo luchevogo porazheniya kozhi pri gennooposredovannoy indukcii angiogeneza preparatom «Neovaskulgen» // Zhurnal anatomii i gistopatologii. 2020. T. 9, № 2. S. 26–34. DOI: 10.18499/2225-7357- 2020- 9-2-26-34

3. Kotenko K.V., Eremin I.I., Moroz B.B., Bushmanov A.Yu., Nadezhina N.M., Galstyan I.A., Grinakovskaya O.S., Aksinenko A.V., Deshevoy Yu.B., Lebedev V.G., Svobodina T.S., Zhgutov Yu.A., Lauk-Dubickiy S.E., Eremin P.S. Kletochnye tehnologii v lechenii radiacionnyh ozhogov: opyt FMBC im. A.I. Burnazyana. // Kletochnaya transplantologiya i tkanevaya inzheneriya. 2012, T. 7, № 2, S. 97–102..

4. Zheng K, Wu W, Yang S, Huang L, Chen J, Gong C et al. Bone Marrow Mesenchymal Stem Cell Implantation for the Treatment of Radioactivity Induced Acute Skin Damage in Rats. // Mol. Med. Rep. 2015, V. 12, № 5. P. 7065-7071.

5. Da Silva Meirelles L, Caplan A, Nardi N. In Search of the In Vivo Identity of Mesenchymal Stem Cells. // Stem Cells. 2008; Vol. 26, № 9, P 2287-2299. DOI:10.1634/Stemcells. 2007-1122.

6. Rastorgueva A.A., Astrelina T.A., Brunchukov V.A., i dr. Ocenka terapevticheskogo potenciala kondicionirovannoy sredy mezenhimal'nyh stvolovyh kletok pri himicheskih ozhogah u laboratornyh zhivotnyh. // Geny i kletki. 2019, T.14, Prilozhenie, S.192–193.

7. Temnov A.A., Astrelina T.A., Rogov K.A., i dr. Issledovanie vliyaniya faktorov kondicionirovannoy sredy, poluchennoy pri kul'tivirovanii mezenhimal'nyh stromal'nyh kletok kostnogo mozga, na techenie tyazhelyh mestnyh luchevyh porazheniy kozhi u krys // Medicinskaya radiologiya i radiacionnaya bezopasnost'. 2018, T. 63, № 1. S. 35–39.

8. Brunchukov V.A., Astrelina T.A., Nikitina V.A., Kobzeva I.V., Suchkova Yu.B., Usupzhanova D.Yu., Rastor­gueva A.A., Karaseva T.V., Gordeev A.V., Maksimova O.A., Naumova L.A., Lischuk S.V., Dubova E.A., Pavlov K.A., Brumberg V.A., Mahova A.E., Lomonosova E.E., Dobrovol'skaya E.I., Barabash I.M., Bushmanov A.Yu., Samoylov A.S. Eksperimental'noe lechenie mestnyh luchevyh porazheniy mezenhimal'nymi stvolovymi kletkami i ih kondicionirovannoy sredoy. Medicinskaya radiologiya i radiacionnaya bezopasnost'. 2020;65(1):5-12. DOI: 10.12737/1024-6177-2020-65-1-5-12

9. Xu S, Liu C, Ji H. Concise Review: Therapeutic Potential of the Mesenchymal Stem Cell Derived Secretome and Extracellular Vesicles for Radiation-Induced Lung Injury: Progress and Hypotheses. // Stem Cells Transl Med. 2019; Vol. 8, № 4, P. 344–354. DOI:10.1002/sctm.18-0038.

10. Zuo R, Liu M, Wang Y et al. Correction to: BM-MSC-Derived Exosomes Alleviate Radiation-Induced Bone Loss by Restoring the Function of Recipient BM-MSCs and Activating Wnt/β-catenin Signaling. // Stem Cell Res Ther. 2020. V. 11, № 1 DOI:10.1186/s13287-020-1553-x.

11. Scuteri A, Donzelli E, Foudah D et al. Mesengenic Differentiation: Comparison of Human and Rat Bone Marrow Mesenchymal Stem Cells. Int J // Stem Cells. 2014; Vol. 7; № 2, P. 127–134. DOI:10.15283/ijsc.2014. 7.2.127.

12. Orbay H, Devi K, Williams P, Dehghani T, Silva E, Sahar D. Comparison of Endothelial Differentiation Capacities of Human and Rat Adipose-Derived Stem Cells. // Plast Reconstr Surg. 2016, Vol. 138, № 6, P. 1231– 1241. DOI:10.1097/prs.0000000000002791.

13. Iacovelli N, Torrente Y, Ciuffreda A et al. Topical Treatment of Radiation-Induced Dermatitis: Current Issues and Potential Solutions. // Drugs Context. 2020. Vol. 9. P. 1–13. DOI:10.7573/dic.2020-4-7

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