Cell and Organ Transplantology. 2015; 3(2):125-132.
Effect of transplantation of cell suspension from embryonic nervous tissue and bone marrow on postischemic cerebral angiogenesis and restoration of limb motor function in rats with experimental ischemic stroke
Iarmoliuk Ie. S.1,2, Tsymbaliuk V. І.1,2, Staino L. P.2, Savchuk О. V.3, Diatel М. V.4
1Bogomolets National Medical University, Kyiv, Ukraine
2A. P. Romodanov State Institute of Neurosurgery NAMS of Ukraine, Kyiv, Ukraine
3Bogomoletz Institute of Physiology NAS of Ukraine, Kyiv, Ukraine
4Kyiv City Oncology Center, Kyiv, Ukraine
Ischemic stroke is one of the leading causes of mortality and disability worldwide. Dispite the progress of medical knowledge and technologies, the rate of permanent neurological impairment in patients after stroke remains high and effective strategy of restorative treatment is still at the stage of experimental development. Restoration of nervous system functions after stroke implies the activation of endogenous reparative processes, such as angiogenesis, using sources of regenerative medicine, including cell and tissue transplantation. Development of optimal and safe methods of neurotransplantation for stroke is one of the priorities of experimental research in this field.
Purpose: to study the effect of post-stroke angiogenesis, stimulated by transplantation of cell suspension from embryonic nervous tissue (TCS-ENT) and bone marrow (TCS-BM), on restoration of motor functions in rats with experimental stroke.
Materials and methods. 160 adult (3-4 months old) outbred albino rats weighing between 280-320 g were divided into groups and subgroups depending on the experimental procedure: with isolated middle cerebral artery occlusion (MCAO), intracerebral allotransplantation of cell suspension from embryonic nervous tissue (MCAO + TCS-ENT),intracerebral autotransplantation of cell suspension from bone marrow (MCAO + TCS-BM) or phosphate-buffered 0.9 % saline infusion (MCAO + PBS) on the 2nd day after MCAO. MCAO was conducted using the modified method of intraluminal monofilament occlusion with blocking of collaterals. Volume of infarction zone was estimated using TTC staining on 7th and 14th day (n = 5 from each group on each day), number of vessels in periinfarct zone was calculated by immunohistochemical staining for CD34 on 7th, 14th and 28th day (n = 6 from each group on each day) after MCAO. Motor deficit was assessed by ledged tapered beam-walking test on 1st, 3rd, 7th, 14th, 21st and 28th day after MCAO (n = 18 from each group on each day).
Results.TCS-BM caused the increase in the number of vessels in the periinfarct zone in dynamics, most prominent on 28th day, and decrease in the volume of infarction zone in comparison with other experimental groups, starting on 7th day after MCAO. TCS-ENT and TCS-BM resulted in regression of motor deficit, starting from 3rd and till 28th day after MCAO. The degree of limb motor asymmetry in rats negatively correlated with the number of vessels in periinfarct zone.
Conclusion. Transplantation of cell suspension from embryonic nervous tissue and bone marrow promotes the regression of motor impairments in experimental animals due to angiogenic effect, which is more prominent in case of TCS-BM.
Key words: middle cerebral artery occlusion, embryonic nervous tissue, bone marrow, angiogenesis, motor deficitFull Text PDF (eng) Full Text PDF (ua)
|1. Volkov AI, Lebedev SV, Viktorov IV, et al. Vlijanie transplantacii nejrogennyh stvolovyh kletok na vosstanovlenie funkcij CNS u krys s insul’tom v kore mozga [Effect of neural stem cells transplantation on the recovery of the central nervous system in rats with stroke in the cerebral cortex]. Zhurnal nevrologii i psihiatrii im. S. S. Korsakova – S. S. Korsakoff Journal of Neurology and Psychiatry. 2010; 12:64-72.|
|4. Potapov IV, Kirillov IA. Stimuljacija angiogeneza kak osnova reparativnogo morfogeneza pri ishemicheskom porazhenii miokarda [Stimulation of reparative angiogenesis as a basis of morphogenesis in ischemic myocardial injury]. Vestnik Ross. AMN – Bulletin of the Russ. AMS. 2007; 9:3-8.|
|6. Yarmoliuk YeS. Dynamika funkcional’nyh porushen’ pry riznyh variantah tkanynnoi’ transplantacii’ z metoju aktyvacii’ angiogenezu na modeli fokal’noi’ cerebral’noi’ ishemii’ v shhuriv [The dynamics of functional impairment in different variants of tissue transplantation to activate angiogenesis on the focal cerebral ischemia model in rats]. Ukrai’ns’kyj naukovo-medychnyj molodizhnyj zhurnal – Ukrainian Scientific Medical Youth Journal. 2014; 82(3):123-127.|
|7. Andres R, Horie N, Slikker W, et al. Human neural stem cells enhance structural plasticity and axonal transport in the ischemic brain. Brain. 2011; 134:1777-1789.
|8. Buhnemann C, Scholz A, Bernreuther C, et al. Neuronal differentiation of transplanted embryonic stem cell-derived precursors in stroke lesions of adult rats. Brain. 2006; 129(12):3238–3248.
|9. Chen J, Chopp M. Intracerebral transplantation of bone marrow with BDNF after MCAo in rat. Neuropharmacology. 2000; 39:711–716.
|10. Chen J-R, Cheng G-Y, Sheu C-C, et al. Transplanted bone marrow stromal cells migrate, differentiate and improve motor function in rats with experimentally induced cerebral stroke. J. Anat. 2008; 213:249–258.
|11. Darsalia V, Kallur T, Kokaia Z. Survival, migration and neuronal differentiation of human fetal striatal and cortical neural stem cells grafted in stroke-damaged rat striatum. Eur. J. Neurosci. 2007; 26(3):605–614.
|12. Deng Y, Ye WB, Hu ZZ, et al. Intravenously administered BMSCs reduce neuronal apoptosis and promote neuronal proliferation through the release of VEGF after stroke in rats. Neurol. Res. 2010; 32(2):148-156.
|13. Freret T, Schumann-Bard P, Boulouard M, et al. On the importance of long-term functional assessment after stroke to improve translation from bench to bedside. Experimental & Translational Stroke Medicine. 2011; 3(6):1-5.
|14. Garlanda C, Dejana E. Heterogeneity of endothelial cells. Specific markers. Arteriosclerosis, Thrombosis and Vascular Biology. 1997; 17:1193-1202.
|15. Gutiérrez-Fernández M, Rodríges-Frutos B, Ramos-Cejudo J, et al. Effects of intravenous administration of allogenic bone marrow- and adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke. Stem Cell Research&Therapy. 2013; 4(11):1-12.
|16. Hayashi T, Noshita N, Sugawara T, et al. Temporal profile of angiogenesis and expression of related genes in the brain after ischemia. J. Cereb. Blood Flow&Metab. 2003; 23:166-180.
|17. Isayama K, Pitts LH, Nishimura MC. Evaluation of 2,3,5-triphenyltetrazolium chloride staining to delineate rat brain infarcts. Stroke. 1991; 22:1394-1398.
|18. Jin K, Mao X-O, Xe L, et al. Transplantation of human neural precursor cells in matrigel scaffolding improves outcome from focal cerebral ischemia after delayed postischemic treatment in rats. J. Cereb. Blood Flow Metab. 2010; 30(3):534-544.
|19. Li Y, Hua XM, Hua F, et al. Are bone marrow regenerative cells ideal seed cells for the treatment of cerebral ischemia? Neural. Regen. Res. 2013; 8(13):1201-1209.
|20. Liman TG, Endres M. New vessels after stroke: postischemic neovascularization and regeneration. Cerebrovasc. Dis. 2012; 33:492-499.
|21. Lu M, Zhu Z, Chopp M, et al. Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ. Res. 2003; 92:692-699.
|22. Mattsson B, Sorensen J C, Zimmer J, et al. Neural grafting to experimental neocortical infarcts improves behavioral outcome and reduces thalamic atrophy in rats housed in enriched but not in standard environments. Stroke. 1997; 28:1225-1232.
|23. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics – 2011 update: a report from the American Heart Association. Circulation. 2011; 123:18-29.
|24. Sawfat MD, Habib F, Elayat A, et al. Morphometric analysis and immunohistochemical study of angiogenic marker expressions in invasive ductal carcinoma of human breast. Folia Morphol. (Warsz.). 2009; 68(3):144-155.|
|25. Schallert T, Woodlee MT. Orienting and placing. Behavior of the laboratory rat: a handbook with tests. Oxford: Oxford University Press. 2005; pp. 129-140.|
|26. Song M, Mohamad O, Gu X, et al. Restoration of intracortical and thalamocortical circuits after transplantation of bone marrow mesenchymal stem cells into the ischemic brain of mice. Cell Transplant. 2013; 22(4):15.
|27. Tsai M-J, Tsai S-K, Hu B-R, et al. Recovery of neurological function of ischemic stroke by application of conditioned medium of bone marrow mesenchymal stem cells derived from normal and cerebral ischemia rats. Journal of Biomedical science. 2014; 21(5):1-12.
|28. Vu Q, Xie K, Eckert M, et al. Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke. Neurology. 2014; 82(14):1277-1286.
|29. Woodruff TM, Thundyil J, Tang S-C, et al. Pathophysiology, treatment, and animal and cellular models of human ischemic stroke. Molecular Neurodegeneration. 2011; 6(11):1-19.
|30. Zhang P, Li J, Liu Y, et al. Human embryonic neural stem cell transplantation increases subventricular zone cell proliferation and promotes peri-infarct angiogenesis after focal cerebral ischemia. Neuropathology. 2011; 31(4):384–391.
|31. Zhang ZG, Zhang L, Zhang Q, et al. Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circ. Res. 2002; 90:284-288.
Iarmoliuk IeS, Tsymbaliuk VІ, Staino LP, Savchuk ОV, Diatel МV. Effect of transplantation of cell suspension from embryonic nervous tissue and bone marrow on postischemic cerebral angiogenesis and restoration of limb motor function in rats with experimental ischemic stroke. Cell and Organ Transplantology. 2015; 3(2):125-132. doi: 10.22494/COT.V3I2.16