Human placenta derived mesenchymal stem cell gel promotes the healing of radiation skin damage in SD rats

doi:10.12307/2021.007

Abstract

Abstract: BACKGROUND: Radiation skin injury has always been a difficult problem in clinical radiotherapy of tumors. A large number of experimental studies have shown that human placenta derived mesenchymal stem cells have the potential for epidermal cell differentiation and can promote the healing of wounded skin.
OBJECTIVE: To evaluate the effect of local application of human placenta derived mesenchymal stem cell gel on the healing of radiation skin damage in rats.
METHODS: Twenty-three Sprague-Dawley rats were randomly divided into three groups: negative control group (n=3), blank gel group (n=10) and mesenchymal stem cell gel group (n=10). Each group received skin irradiation of buttock and back (6 meV electron wire, total dose of 50 Gy, irradiation field of 3 cm×3 cm, single dose rate of 500 cGy/min). At 23 days after irradiation, the wounds of the mesenchymal stem cell gel group were smeared with human placenta derived mesenchymal stem cell gel. The blank gel control group was smeared with blank gel evenly, once a day, for six times. The negative control group was not given any treatment. The wound healing was observed once every four days. After 28 days of treatment, the effects of human placenta derived mesenchymal stem cell gel on inflammatory cells, wound microvessel density and wound collagen fibers were observed.
RESULTS AND CONCLUSION: (1) The skin in the negative control group was swollen and ulcerated; the skin in the blank gel group was stiff and shrunken; and the wounds did not heal during the observation. The mesenchymal stem cell gel group developed new epithelial tissue in the irradiation area, and the wound healing was complete during the observation. (2) Compared with negative control and blank gel groups, at 16, 20, 24, and 28 days after treatment, the wound healing speed of the mesenchymal stem cell gel group was significantly faster (P < 0.05), and wound area was significantly reduced (P < 0.05); the count of inflammatory cells was lower (P < 0.05); count of CD31 cells in microvessel was significantly higher (P < 0.05); collagen fibers were arranged orderly. (3) The results indicate that local application of human placenta derived mesenchymal stem cell gel can promote the healing of radiation skin damage in SD rat.

Key words: stem cells, human placenta derived mesenchymal stem cells, radiation skin damage, vascularization, healing, inflammation, collagen fiber, rat

CLC Number:

Xu Xiaoming, Chen Yan, Song Qian, Yuan Lu, Gu Jiaming, Zhang Lijuan, Geng Jie, Dong Jian. Human placenta derived mesenchymal stem cell gel promotes the healing of radiation skin damage in SD rats[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(25): 3976-3980.

Figures/Tables 6

References

[1] RYAN JL. Ionizing radiation: the good, the bad, and the ugly. J Invest Dermatol. 2012;132(3 Pt 2):985-993.
[2] KIM JH, KOLOZSVARY AJ, JENROW KA, et al. Mechanisms of radiation-induced skin injury and implications for future clinical trials. Int J Radiat Biol. 2013;89(5):311-318.
[3] STONE HB, COLEMAN CN, ANSCHER MS, et al. Effects of radiation on normal tissue: consequences and mechanisms. Lancet Oncol. 2003;4(9):529-536.
[4] MÜLLER K, MEINEKE V. Radiation-induced alterations in cytokine production by skin cells. Exp Hematol. 2007;35(4 Suppl 1):96-104.
[5] 张倩玉,许斌,张惠博,等. SD大鼠急性放射性皮炎模型的建立[J]. 现代生物医学进展,2018,18(8):1419-1424.
[6] DOUGLAS BG, FOWLER JF. The effect of multiple small doses of X rays on skin reactions in the mouse and a basic interpretation. 1976. Radiat Res. 2012;178(2):AV125-138.
[7] HOELLER U, TRIBIUS S, KUHLMEY A, et al. Increasing the rate of late toxicity by changing the score? A comparison of RTOG/EORTC and LENT/SOMA scores. Int J Radiat Oncol Biol Phys. 2003;55(4):1013-1018.
[8] RANDALL K, COGGLE JE. Expression of transforming growth factor-beta 1 in mouse skin during the acute phase of radiation damage. Int J Radiat Biol. 1995;68(3):301-309.
[9] SORIANO JL, CALPENA AC, SOUTO EB, et al. Therapy for prevention and treatment of skin ionizing radiation damage: a review. Int J Radiat Biol. 2019;95(5):537-553.
[10] 朱琳,李薇薇,刘志凯.人血管基质片段联合脂肪干细胞促进裸鼠放射性皮肤损伤的愈合[J].山东大学学报(医学版),2017,55(9):66-72.
[11] ZHAO N, YUE Z, CUI J, et al. IGF-1C domain-modified hydrogel enhances therapeutic potential of mesenchymal stem cells for hindlimb ischemia. Stem Cell Res Ther. 2019;10(1):129.
[12] MERAVIGLIA V, VECELLIO M, GRASSELLI A, et al. Human chorionic villus mesenchymal stromal cells reveal strong endothelial conversion properties. Differentiation. 2012;83(5):260-270.
[13] TAO H, HAN Z, HAN ZC, et al. Proangiogenic Features of Mesenchymal Stem Cells and Their Therapeutic Applications. Stem Cells Int. 2016;2016:1314709.
[14] GERHARD-HERMAN MD, GORNIK HL, BARRETT C, et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135(12):e686-e725.
[15] ZHANG K, ZHAO X, CHEN X, et al. Enhanced Therapeutic Effects of Mesenchymal Stem Cell-Derived Exosomes with an Injectable Hydrogel for Hindlimb Ischemia Treatment. ACS Appl Mater Interfaces. 2018;10(36): 30081-30091.
[16] 韩忠朝,王伟强. 间充质干细胞的生物学特性及临床应用[J].中国科学:生命科学,2017,47(12):1404-1409.
[17] DU WJ, CHI Y, YANG ZX, et al. Heterogeneity of proangiogenic features in mesenchymal stem cells derived from bone marrow, adipose tissue, umbilical cord, and placenta. Stem Cell Res Ther. 2016;7(1):163.
[18] RASULOV MF, VASILCHENKOV AV, ONISHCHENKO NA, et al. First experience of the use bone marrow mesenchymal stem cells for the treatment of a patient with deep skin burns. Bull Exp Biol Med. 2005;139(1):141-144.
[19] LIANG L, LI Z, MA T, et al. Transplantation of Human Placenta-Derived Mesenchymal Stem Cells Alleviates Critical Limb Ischemia in Diabetic Nude Rats. Cell Transplant. 2017;26(1):45-61.
[20] 韩忠朝,耿洁,梁璐. 一种用于创面修复的干细胞制剂及其制备方法:中国, CN 201210133427 [P]. 2012-09-19.
[21] DU W, LI X, CHI Y, et al. VCAM-1+ placenta chorionic villi-derived mesenchymal stem cells display potent pro-angiogenic activity. Stem Cell Res Ther. 2016;7:49.
[22] ZENG X, TANG Y, HU K, et al. Three-week topical treatment with placenta-derived mesenchymal stem cells hydrogel in a patient with diabetic foot ulcer: A case report. Medicine (Baltimore). 2017;96(51):e9212.