This journal is
indexed in Scopus
Year 2019 Vol. 27 No 1
I.V. MAIBORODIN 1, N.F. FIGURENKO 1, A.A. ELOVSKIY 2, T.V. MIKHEEVA 1, R.V. MASLOV 1, V.I. MAIBORODINA 3, A.I. SHEVELA 1
POSSIBILITY OF INFLAMMATORY INJURES DEVELOPMENT IN INTACT LIVER AFTER THE MULTIPOTENT STROMAL CELL INJECTION IN EXPERIMENT
Institute of Chemical Biology and Fundamental Medicine1,
Medical Center “Avicenna” 2,
Institute of Molecular Pathology and Pathomorphology, Federal Research Center for Fundamental and Translational Medicine3,
The Russian Federation
Objective. To study the possibility of complications development after the injection of the autologous multipotent mesenchymal stromal cells of the bone marrow origin (MMSC) directly in the intact liver of rats.
Methods. The changes of the rat liver after the direct injection of MMSC with a transfected GFP-gene and additionally stained cellular membranes by Vybrant® CM-Dil were investigated by the methods of light microscopy with luminescence application.
Results. After the MMSC injections, the extensive congestions, depot of the injected cells in the liver were absent in all animals even after a week. In some cases, up to 1/3 observations, the aseptic inflammation manifested by the dilation and hyperemia of sinusoids, an increase of neutrophil number in the sinusoids, necroses of parenchyma and lympho-histiocytic infiltrates were developed in the organ. Long thin layers of the connective tissue extending in the vessel region and containing a large number of siderophages appeared in the liver during the 3rd week. By the 4th week the specified liver morphological changes have normalized. Throughout the experiment there was no any differentiation of injected MMSC to the liver cells.
Conclusions. The main causes of the revealed changes are the damage of the liver parenchyma at the cell suspension injection under pressure and also direct presence of MMSC and their detritus. At the syringe under pressure the MMSC suspension moves apart and lacerates the liver parenchyma along the vessels. Injected MMSC, some of which quickly perishes due to a dramatic change in living conditions, and also the detritus which is present together with them, immediately cause migration of macrophages to the site of injection and actually are the reason of aseptic inflammatory process. MMSC are quickly eliminated from the injection site in the liver by macrophages and also by means of vascular and lymphatic beds whereas the proceeding inflammatory reaction damages the liver cells and serves as the cause of the revealed changes.
- Qu M, Yuan X, Liu D, Ma Y, Zhu J, Cui J, Yu M, Li C, Guo D. Bone marrow-derived mesenchymal stem cells attenuate immune-mediated liver injury and compromise virus control during acute hepatitis b virus infection in mice. Stem Cells Dev. 2017 Jun 1;26(11):818-27. doi: 10.1089/scd.2016.0348
- Haga H, Yan IK, Borrelli DA, Matsuda A, Parasramka M, Shukla N, Lee DD, Patel T. Extracellular vesicles from bone marrow-derived mesenchymal stem cells protect against murine hepatic ischemia/reperfusion injury. Liver Transpl. 2017 Jun;23(6):791-803. doi: 10.1002/lt.24770
- Maiborodin IV, Morozov VV, Anikeev AA, Figurenko NF, Maslov RV, Chastikin GA, Matveeva VA, Maiborodina VI. Macrophage reaction to multipotent mesenchymal stromal cells introduction into surgical trauma site in rats. Novosti Khirurgii. 2017;25(3):233-41. doi: 10.18484/2305-0047.2017.3.23 (in Russ.)
- Li F, Yang M, Wang L, Williamson I, Tian F, Qin M, Shah PK, Sharifi BG. Autofluorescence contributes to false-positive intracellular Foxp3 staining in macrophages: a lesson learned from flow cytometry. J Immunol Methods. 2012 Dec 14;386(1-2):101-7. doi: 10.1016/j.jim.2012.08.014
- Mendes-Jorge L, Ramos D, Luppo M, Llombart C, Alexandre-Pires G, Nacher V, Melgarejo V, Correia M, Navarro M, Carretero A, Tafuro S, Rodriguez-Baeza A, EsperanÇa-Pina JA, Bosch F, Ruberte J. Scavenger function of resident autofluorescent perivascular macrophages and their contribution to the maintenance of the blood-retinal barrier. Invest Ophthalmol Vis Sci. 2009 Dec;50(12):5997-6005. doi: 10.1167/iovs.09-3515
- Lei L, Tzekov R, Tang S, Kaushal S. Accumulation and autofluorescence of phagocytized rod outer segment material in macrophages and microglial cells. Mol Vis. 2012;18:103-13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265176
- Luhmann UF, Robbie S, Munro PM, Barker SE, Duran Y, Luong V, Fitzke FW, Bainbridge JW, Ali RR, MacLaren RE. The drusenlike phenotype in aging Ccl2-knockout mice is caused by an accelerated accumulation of swollen autofluorescent subretinal macrophages. Invest Ophthalmol Vis Sci. 2009 Dec;50(12):5934-43. doi: 10.1167/iovs.09-3462
- Mitchell AJ, Pradel LC, Chasson L, Van Rooijen N, Grau GE, Hunt NH, Chimini G. Technical advance: autofluorescence as a tool for myeloid cell analysis. J Leukoc Biol. 2010 Sep;88(3):597-603. doi: 10.1189/jlb.0310184
- Liu S, Jiang L, Li H, Shi H, Luo H, Zhang Y, Yu C, Jin Y. Mesenchymal stem cells prevent hypertrophic scar formation via inflammatory regulation when undergoing apoptosis. J Invest Dermatol. 2014 Oct;134(10):2648-57. doi: 10.1038/jid.2014.169
- Yates CC, Nuschke A, Rodrigues M, Whaley D, Dechant JJ, Taylor DP, Wells A. Improved transplanted stem cell survival in a polymer gel supplemented with tenascin c accelerates healing and reduces scarring of murine skin wounds. Cell Transplant. 2017 Jan 24;26(1):103-13. doi: 10.3727/096368916X692249
- Babaei A, Katoonizadeh A, Ranjbar A, Naderi M, Ahmadbeigi N. Directly injected native bone-marrow stem cells cannot incorporate into acetaminophen-induced liver injury. Biologicals. 2018 Mar;52:55-58. doi: 10.1016/j.biologicals.2017.12.006
- Abdelhamid L, Hussein H, Ghanem M, Eissa N. Retinoic acid-mediated anti-inflammatory responses in equine immune cells stimulated by LPS and allogeneic mesenchymal stem cells. Res Vet Sci. 2017 Oct;114:225-232. doi: 10.1016/j.rvsc.2017.05.006
- Gavrilin VN, Shkurupii VA. Vliianie nakopleniia polivinilpirrolidona v sinusoidal’nykh kletkakh pecheni na kharakter toksicheskogo povrezhdeniia organa. Biul SO RAMN. 1995;15(2):24-28.(in Russ.)
630090, The Russian Federation,
Novosibirsk, Ac. Lavrentyev Ave., 8,
Institute of Chemical Biology
and Fundamental Medicine,
Center of Innovative Medical Technologies.
Igor V. Maiborodin
Maiborodin Igor V., MD, Professor, Chief Researcher of the Stem Cell Laboratory, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russian Federation.
Figurenko Nikolay F., PhD, Applicant for Doctor’s Degree of the Stem Cell Laboratory, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russian Federation.
Elovskiy Aleksandr A., Anesthesiologist-Resuscitator-Transfusiologist of the Anesthesiology and Resuscitation Unit, Medical Center “Avicenna”, Novosibirsk, Russian Federation.
Mikheeva Tatiana V., PhD, Applicant for Doctor’s Degree of the Stem Cell Laboratory, Institute of Chemical Bio Ðîìàílogy and Fundamental Medicine, Novosibirsk, Russian Federation.
Maslov Roman V., PhD, Applicant for Doctor’s Degree of the Stem Cell Laboratory, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russian Federation.
Maiborodina Vitalina I., MD, Leading Researcher of the Laboratory of Ultrastructural Basis of Pathology, Institute of Molecular Pathology and Pathomorphology, Novosibirsk, Russian Federation.
Shevela Andrey I., MD, Professor, Head of the Unit “Center of innovative medical technologies”, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russian Federation.