The Role of Cord Blood in the Regulation of the Cellular and Humoral Link of Immunity in Experimental Atopic Dermatitis

Authors

  • Hanna Koval Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Ukraine
  • Olena Lutsenko Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Ukraine https://orcid.org/0000-0003-3982-9687
  • Mykola Bondarovych Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Ukraine https://orcid.org/0000-0001-7977-0283
  • Maksym Ostankov Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Ukraine https://orcid.org/0000-0001-8412-5262
  • Anatoliy Goltsev Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine; Interdepartmental Research Center of Cryobiology and Cryomedicine, NAS of Ukraine, AMS of Ukraine and Ministry of Health of Ukraine, Ukraine https://orcid.org/0000-0002-5289-5876

DOI:

https://doi.org/10.20535/ibb.2021.5.3.238976

Keywords:

atopic dermatitis, cord blood leucoconcentrate, immune system, cryopreservation, lyophilization

Abstract

Background. Atopic dermatitis (AD) as one of the most common diseases of autoimmune genesis in the structure of dermatological practice, is characterized by itching, dryness, thickening of the skin, characteristic rashes. The drugs of choice in the treatment of AD are steroidal anti-inflammatory drugs. However, the development of unwanted side effects is a serious problem attributed to using hormone therapy. The search for effective methods of treating AD is an urgent task of medicine and in particular dermatology. At the same time, there is an obvious need for the participation in the solution of this problem also of specialists-immunologists working in the field of application of cell therapy drugs, acting on various pathogenetic links of the disease. The development of new or optimization of existing methods of treating AD is the urgent task facing them.

Objective. Evaluation of the immunocorrective effect of lyophilized (lHCBL) and cryopreserved human cord blood leucoconcetrate (cHCBL) on a AD model.

Methods. The experiments were carried out on 6-month-old Wistar rats. Upon induction of AD, the inflammation focus was formed on the rat's back (9–10 cm2) by daily rubbing in a 5% alcohol-acetone solution of dinitrochlorobenzene (DNCB) for 21 days. cHCBL and lHCBL were injected intraperitoneally, 0.5 ml at a dose of 5´106 cells in one day after the final DNCB treatment. The adhesive and phagocytic activity of the cells of the peritoneal cavity, the level of circulating immune complexes, the population and subpopulation of lymphocytes (CD3+, CD4+, CD8+, CD16+, CD4+CD25+), the immunoregulatory index of lymphocytes, the concentration of immunoglobulins in the blood serum were determined.

Results. For AD induced by DNCB, systemic changes in the immune status are characteristic, which is expressed by changes in the parameters of cellular and humoral immunity. The most fundamental changes in cell subpopulations in spleen of rats with AD were revealed: a decrease in the number of total T-lymphocytes and their two main subpopulations (CD4+ and CD8+ cells). Against this background, changes were noted in the monocytic-phagocytic and humoral systems of immunity. The paper shows the effectiveness of the use of cHCBL and lHCBL in the correction of pathological manifestations of experimental AD. On the background of treatment, the features of the immunocorrective effect of each of the drugs were noted. Thus, when assessing intergroup values, a more pronounced increase in T-reg was revealed in rats of the 5th group – 3.9 [3.8; 4.0] versus 3.2 [3.0; 3.3] in the 4th group (P < 0.01); IgA level – 1.6 [1.5; 1.7] versus 1.3 [1.2; 1.4] (P < 0.01).

Conclusions. Thus, lHCBL exhibits immunocorrective activity in the treatment of experimental AD, surpassing in some parameters the activity of сHCBL, which is promising for its use in clinical practice.

References

Schmidt AD, de Guzman Strong C. Current understanding of epigenetics in atopic dermatitis. Exp Dermatol. 2021;30(8):1150-5. DOI: 10.1111/exd.14392

Narla S, Silverberg JI. Association between atopic dermatitis and autoimmune disorders in US adults and children: A cross-sectional study. J Am Acad Dermatol. 2019;80(2):382-9. DOI: 10.1016/j.jaad.2018.09.025

Abreu D, Kim BS. Innate immune regulation of dermatitis. Immunol Allergy Clin North Am. 2021;41(3):347-59. DOI: 10.1016/j.iac.2021.04.011

Gavrilova T. Immune dysregulation in the pathogenesis of atopic dermatitis. Dermatitis. 2018;29(2):57-62. DOI: 10.1097/DER.0000000000000340

Klaeschen AS, Nümm TJ, Herrmann N, Leib N, Maintz L, Sakai T, et al. JAK1/2 inhibition impairs the development and function of inflammatory dendritic epidermal cells in atopic dermatitis. J Allergy Clin Immunol. 2021 Jun;147(6):2202-12.e8. DOI: 10.1016/j.jaci.2020.11.041

David Boothe W, Tarbox JA, Tarbox MB. Atopic Dermatitis: Pathophysiology. Adv Exp Med Biol. 2017;1027:21-37. DOI: 10.1007/978-3-319-64804-0_3

Furue M, Chiba T, Tsuji G, Ulzii D, Kido-Nakahara M, Nakahara T, et al. Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies. Allergol Int. 2017 Jul;66(3):398-403. DOI: 10.1016/j.alit.2016.12.002

Akkoc T, de Koning PJ, Rückert B, Barlan I, Akdis M, Akdis CA. Increased activation-induced cell death of high IFN-gamma-producing T(H)1 cells as a mechanism of T(H)2 predominance in atopic diseases. J Allergy Clin Immunol. 2008;121(3):652-8.e1. DOI: 10.1016/j.jaci.2007.12.1171

Su C, Yang T, Wu Z, Zhong J, Huang Y, Huang T, et al. Differentiation of T-helper cells in distinct phases of atopic dermatitis involves Th1/Th2 and Th17/Treg. Eur J Inflam. 2017;15(1):46-52. DOI: 10.1177/1721727X17703271

Li Y, Xu W, Yao J, Cheng H, Sun X, Li L. Correlation of blood FoxP3+ regulatory T cells and disease activity of atopic dermatitis. J Immunol Res. 2019;2019:1820182. DOI: 10.1155/2019/1820182

Agrawal R, Wisniewski JA, Woodfolk JA. The role of regulatory T cells in atopic dermatitis. Curr Probl Dermatol. 2011;41:112-24. DOI: 10.1159/000323305

Ratchataswan T, Banzon TM, Thyssen JP, Weidinger S, Guttman-Yassky E, Phipatanakul W. Biologics for treatment of atopic dermatitis: current status and future prospect. J Allergy Clin Immunol Pract. 2021;9(3):1053-65. DOI: 10.1016/j.jaip.2020.11.034

Yang N, Chen Z, Zhang X, Shi Y. Novel targeted biological agents for the treatment of atopic dermatitis. BioDrugs. 2021;35(4):401-15. DOI: 10.1007/s40259-021-00490-x

Daltro SRT, Meira CS, Santos IP, Ribeiro Dos Santos R, Soares MBP. Mesenchymal stem cells and atopic dermatitis: A review. Front Cell Dev Biol. 2020;8:326. DOI: 10.3389/fcell.2020.00326

Poggi A, Zocchi MR. Immunomodulatory properties of mesenchymal stromal cells: still unresolved "Yin and Yang". Curr Stem Cell Res Ther. 2019;14(4):344-50. DOI: 10.2174/1574888X14666181205115452

Goltsev AN, Falko OV, Volina VV, Lipina OV, Prokopyuk OS, Gulevsky OK. Morphological study of liver in rats with toxic hepatitis after application of cryopreserved human cord blood serum. Probl Cryobiol Cryomed. 2018;28(1):014-8. DOI: 10.15407/cryo28.01.014

Goltsev KA, Volina VV, Kozhina OYu, Ostankov MV. Effect of cryopreserved cord blood on structure of immunocompe-tent and other vital organs at acute pyoperitonitis. Probl Cryobiol. 2011;21(4):429-44.

Kozhina OYu, Ostankov MV, Ostankova LV, Bondarovich NA, Goltsev AN. Effect of cryopreserved cord blood on ac-tivity of alveolar macrophages in experimental model of influenza. Probl Cryobiol Cryomed. 2013;23(3):247-59.

Berglund S, Magalhaes I, Gaballa A, Vanherberghen B, Uhlin M. Advances in umbilical cord blood cell therapy: the pre-sent and the future. Expert Opin Biol Ther. 2017;17(6):691-9. DOI: 10.1080/14712598.2017.1316713

Srivastava AK, Prabhakara KS, Kota DJ, Bedi SS, Triolo F, Brown KS, et al. Human umbilical cord blood cells restore vascular integrity in injured rat brain and modulate inflammation in vitro. Regen Med. 2019;14(4):295-307. DOI: 10.2217/rme-2018-0106

Zhang J, Lv S, Liu X, Song B, Shi L. Umbilical cord mesenchymal stem cell treatment for Crohn's disease: a randomized controlled clinical trial. Gut Liver. 2018;12(1):73-8. DOI: 10.5009/gnl17035

Qi T, Gao H, Dang Y, Huang S, Peng M. Cervus and cucumis peptides combined umbilical cord mesenchymal stem cells therapy for rheumatoid arthritis. Medicine (Baltimore). 2020;99(28):e21222.

Kassem DH, Kamal MM. Therapeutic efficacy of umbilical cord-derived stem cells for diabetes mellitus: a meta-analysis study. Stem Cell Res Ther. 2020;11(1):484. DOI: 10.1186/s13287-020-01996-x

Kang SY, Park DE, Song WJ, Bae BR, Lee JW, Sohn KH, et al. Immunologic regulatory effects of human umbilical cord blood-derived mesenchymal stem cells in a murine ovalbumin asthma model. Clin Exp Allergy. 2017;47(7):937-45. DOI: 10.1111/cea.12920

Kan XL, Pan XH, Zhao J, He J, Cai XM, Pang RQ, et al. Effect and mechanism of human umbilical cord mesenchymal stem cells in treating allergic rhinitis in mice. Sci Rep. 2020;10(1):19295. DOI: 10.1038/s41598-020-76343-4

Sirous MA, Goltsev AN, Rassokha IV, Goltsev KA. Application of cryopreserved fetal liver cells to treat autoimmune haemolytic anemia. Probl Cryobiol. 2010;20(2):217.

Koval GK, Lutsenko OD, Grisha IG, Sokil LV, Bondarovych MO, Ostankov MV, et al. Impact of lyophilisation on integrity of structural and functional characteristics of human cord blood leukoncentrate. Probl Cryobiol Cryomed. 2019;29(4):332-43. DOI: 10.15407/cryo29.04.332

Goltsev AM, Mosiichuk VV, Goltsev KA, Tarannik HK, Sokil LV, Ostankov MV, et al., inventors; IPC&C NAS of Ukraine, assignee. Method for lyophilization of cord blood leukoconcentrate. Ukraine patent 117780U. 2017 July 10.

Tsutsaieva AO, Hryschenko VI, Kudokotseva OV, Schehlov AV, Tupchiienko HS, Prokoliuk OS, inventors; IPC&C NAS of Ukraine, assignee. Method for cryopreservation of hemopoietic cells of cord blood. Ukraine patent 31847А. 2000 Dec 15.

Zalkan PM, Ievleva EA. Experimental model of allergic dermatitis. In: Dolgov AP, Raben AS, Antonev AA, editors. Topi-cal issues of professional dermatology. Moscow: Meditsina; 1965. p. 106-12.

Paster YeU, Ovod VV, Pozur VK, Vikhot' NE. Immunology laboratory course. Kyiv: Vyshcha Shkola; 1989. 304 p.

Menshykov VV. Laboratory research methods in the clinic. Moscow: Meditsina; 1987. p. 123-5.

García EM, Galicia-Carreón J, Novak N. In vitro conversion into CD4+CD25+Foxp3+ induced regulatory T cells is reduced in atopic dermatitis patients. Int Arch Allergy Immunol. 2020;181(5):353-6. DOI: 10.1159/000506285

Li Y, Xu W, Yao J, Cheng H, Sun X, Li L. Correlation of blood FoxP3+ regulatory T cells and disease activity of atopic dermatitis. J Immunol Res. 2019 Sep 15;2019:1820182. DOI: 10.1155/2019/1820182

Olivry T, Wofford J, Paps JS, Dunston SM. Stratum corneum removal facilitates experimental sensitization to mite aller-gens in atopic dogs. Vet Dermatol. 2011;22(2):188-96. DOI: 10.1111/j.1365-3164.2010.00938.x

Simpson A, Maeda S, Marsella R. Temporal dynamic changes of phenotypic expression of peripheral CD4 cells during en-vironmental allergen challenge in an experimental model of canine atopic dermatitis: a pilot study. J Vet Med Sci. 2009;71(9):1177-81. DOI: 10.1292/jvms.71.1177

Ling EM, Smith T, Nguyen XD, Pridgeon C, Dallman M, Arbery J, et al. Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet. 2004;363(9409):608-15. DOI: 10.1016/S0140-6736(04)15592-X

Taylor AL, Hale J, Hales BJ, Dunstan JA, Thomas WR, Prescott SL. FOXP3 mRNA expression at 6 months of age is higher in infants who develop atopic dermatitis, but is not affected by giving probiotics from birth. Pediatr Allergy Immu-nol. 2007;18(1):10-9. DOI: 10.1111/j.1399-3038.2006.00483.x

Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, Niwa A, et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity. 2009;30(6):899-911. DOI: 10.1016/j.immuni.2009.03.019

Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 2008;322(5899):271-5. DOI: 10.1126/science.1160062

Klaihmon P, Luanpitpong S, Lorthongpanich C, Laowtammathron C, Waeteekul S, Terbto P, et al. Episomal vector re-programming of human umbilical cord blood natural killer cells to an induced pluripotent stem cell line MUSIi013-A. Stem Cell Res. 2021;55:102472. DOI: 10.1016/j.scr.2021.102472

Goltsev AM, Fuller BJ, Bondarovych MO, Babenko NM, Gaevska YuO, Buriak IA, et al. COVID-19 as a potential target for cryobiology and cryomedicine. Probl Cryobiol Cryomed. 2020;30(2):107-31. DOI: 10.15407/cryo30.02.107

Mirazi N, Baharvand F, Moghadasali R, Nourian A, Hosseini A. Treatment with human umbilical cord blood serum in a gentamicin-induced nephrotoxicity model in rats. Drug Chem Toxicol. 2021 May 18;1-7. DOI: 10.1080/01480545.2021.1926475

Maharajan N, Cho GW, Choi JH, Jang CH. Regenerative therapy using umbilical cord serum. In Vivo. 2021;35(2):699-705. DOI: 10.21873/invivo.12310

Goltsev AN, Babenko NN. Stipulation of the possibility to use embryonic neuronal cells when treating organ-specific au-toimmune diseases. Probl Cryobiol. 2003;2:49-61.

Ostankov MV, Bondarovich NA, Rassokha IV, Goltsev AN. Substantiation of the possibility of use of embryonic nerve cells in treatment of organ-specific autoimmune diseases. Probl Cryobiol. 2008;18(3):302-5.

Cacheiro-Llaguno C, Parody N, Escutia MR, Carnés J. Role of circulating immune complexes in the pathogenesis of canine leishmaniasis: New players in vaccine development. Microorganisms. 2021 Mar 30;9(4):712. DOI: 10.3390/microorganisms9040712

Published

2021-09-22

How to Cite

1.
Koval H, Lutsenko O, Bondarovych M, Ostankov M, Goltsev A. The Role of Cord Blood in the Regulation of the Cellular and Humoral Link of Immunity in Experimental Atopic Dermatitis. Innov Biosyst Bioeng [Internet]. 2021Sep.22 [cited 2024Apr.26];5(3):167-7. Available from: http://ibb.kpi.ua/article/view/238976

Issue

Section

Articles