The efficacy of fetal neural cell aggregates and their combination with fetal liver stromal cells to reduce brain damage after intracerebral hemorrhage in rats

Home/2021, Vol. 9, No. 1/The efficacy of fetal neural cell aggregates and their combination with fetal liver stromal cells to reduce brain damage after intracerebral hemorrhage in rats

Cell and Organ Transplantology. 2021; 9(1):22-28.
DOI: 10.22494/cot.v9i1.118

The efficacy of fetal neural cell aggregates and their combination with fetal liver stromal cells to reduce brain damage after intracerebral hemorrhage in rats

Zolotko K.1, Sukach O.1,2, Kompaniets A.1

  • 1Institute for Problems of Cryobiology and Сryomedicine, National Academy of Sciences of Ukraine, Kharkiv, Ukraine
  • 2H. S. Skovoroda Kharkiv National Pedagogical University, Kharkiv, Ukraine


Patients with intracerebral hemorrhage have frequent complications and high mortality. There are currently no effective treatments for this disease. We investigated the effect of the use of cryopreserved aggregates of neural cells in combination with fetal liver stromal cells on the reduction of rat brain injury after intracerebral hemorrhage.
Methods. Intracerebral hemorrhage (ICH) was modeled in rats by stereotactic administration of 0.2 U of collagenase type IV into the striatum. Neural cell obtained from brain and stromal cells (SCs) – from liver of rat fetuses of 15 dpc. The suspension of neural cell aggregates (NCAs) alone or in combination with fetal liver stromal cells was injected into the lateral ventricle.
The level of lipid peroxidation was determined by the thiobarbituric acid test. The degree of brain cells injury after ICH was determined by the activity of lactate dehydrogenase in blood serum. To assess the intensity of adverse factors and the regenerative potential of different variants of cell therapy, the area of the lost striatum in the rat brain and the average distance from the border of the lesion to the nearest neurons were determined.
Results. Combined transplantation of NCAs with fetal liver SCs in rats with ICH was found to reduce malonic dialdehyde concentration and lactate dehydrogenase activity more effectively than NCAs alone, indicating inhibition of lipid peroxidation and reduction of cell injury after intracerebral hemorrhage as a result of the addition of SCs. It was shown a significant decrease in the area of lost striatum in both experimental groups. The single administration of NCAs reduced the distance from the lesion border to the nearest neurons the most, indicating the best conditions for survival and/or regeneration of neurons close to the lesion compared to controls.
Conclusions. Administration of NCAs, both alone and in combination with fetal liver SCs, reduces the intensity of oxidative stress, preserves the intact striatum tissue, and increases the number of neurons near the brain lesion in intracerebral hemorrhage in rats. The co-transplantation of fetal liver SCs helps to inhibit lipid peroxidation more effectively.

Key words: intracerebral hemorrhage; neural cells aggregates; fetal liver stromal cells; stereotaxis

Full Text PDF

1. Poon MT, Fonville AF, Al-Shahi Salman R. Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2014; 85(6):660-667.
2. Detante O, Jaillard A, Moisan A, et al. Bioterapies in stroke. Rev Neurol. 2014; 170: 779-798.
3. Sukach АN, Lebedinsky AS, Otchenashko OV, et al. Transplantation of cryopreserved rat fetal neural cells in suspension and in multicellular aggregates into rats with spinal cord injury. Cell Organ Transpl. 2016; 4(1):22-28. DOI: 10.22494/COT.V4I1.5
4. Zolotko KM, Sukach AN, Kompaniets AM. [The dynamics of behavioral tests in rats with intracerebral hemorrhage after the injection of cryopreserved neural cells]. Visnyk problem biologii i medytsyny. 2019; 3(152):108-112. DOI: 10.29254/2077-4214-2019-3-152-108-112. [In Russian].
5. Prockop DJ, Oh JY. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. MolTher. 2012; 20(1):14-20. DOI: 10.1038/mt.2011.211.
PMid:22008910 PMCid:PMC3255583
6. MacLellan CL, Silasi G, Poon CC, et al. Intracerebral hemorrhage models in rat: comparing collagenase to blood infusion. J Cereb Blood Flow Metab. 2008; 28:516-525. DOI:10.1038/sj.jcbfm.9600548.
7. Chen AZ, Liu N, Huang H, et al. Outgrowth of neuronal axons on adipose-derived stem cell transplanting for treatment of cerebral infarction in rats. Cell Mol Immunol. 2011; 27(8):868-871.
8. Nonaka M, Yoshikawa M, Nishimura F, et al. Intraventricular transplantation of embryonic stem cell-derived neural stem cells in intracerebral hemorrhage rats. Neurol Res. 2004; 26(3): 265-272. DOI: 10.1179/016164104225014049.
9. Sukach OM. Inventor Institute for problems of cryobiology and cryomedicine National academy of sciences of Ukraine, assignee. [The method of neural precursor cells obtaining]. Patent of Ukraine 119411. 2017 September 25. [In Ukrainian].
10. Sukach AN, Shevchenko MV, Liashenko TD. Comparative study of influence on fetal bovine serum and serum of adult rat on cultivation of newborn rat neural cells. Biopolym Cell. 2014; 30(5):394-400.
11. Sukach AN, Liashenko TD, Shevchenko MV. [Properties of the isolated cells of newborn rats’ nervous tissue in culture]. Biotechnol Acta. 2013; 6(3):63-68. [In Russian].
12. Petrenko AYu, Sukach AN. Isolation of intact mitochondria and hepatocytes using vibration. Analytical Biochem. 1991; 194(2):326-29.
13. Hoppo T, Fujii H, HiroseT, et al. Thy1-positive mesenchymal cells promote the maturation of CD49f-positive hepatic progenitor cells in the mouse fetal liver. Hepatology. 2004; 39:1362-70.
14. Schmelzer E. Zhang L, Bruce A, et al. Human hepatic stem cells from fetal and postnatal donors. J Exp Med. 2007; 204:1973-87.
PMid:17664288 PMCid:PMC2118675
15. Han N, Ding S, Wu T, Zhu Y. Correlation of free radical level and apoptosis after intracerebral hemorrhage in rats. Neurosci Bull. 2008; 24(6):351-358. DOI: 10.1007/s12264-008-0711-4.
PMid:19037320 PMCid:PMC5552598
16. Wang G, Yang Q, Li G, Wang L, Hu W, Tang, et al. Time course of heme oxygenase-1 and oxidative stress after experimental intracerebral hemorrhage. ActaNeurochir. 2011; 153(2):319-325.DOI: 10.1007/s00701-010-0750-2.
17. Andreeva LN. Modifikatsiya metoda opredeleniya perekisey lipidov v teste s tiobarbiturovoy kislotoy. [Modification of the method for determining lipid peroxides in the test with thiobarbituric acid]. Laboratornoe delo – Laboratory work. 1988; 11:41-43. [In Russian].
18. Glantz S. Mediko-biologicheskaya statistika [Biomedical statistics]. Moskva: Praktika – Moscow: Practice. 1998, 459 p. [In Russian].
19. Pohlert T. The pairwise multiple comparison of mean ranks package (PMCMR). R package. New York: CRAN.R-project, 2016.
20. Ross MH, Pawlina W. Histology. A text and atlas with correlated cell and molecular biology. 7th ed. Gainseville: WoltersKluwerl; 2016. 1002 p.
21. Beray-Berthat V, Delifer C, Besson VC, et al. Long-term histological and behavioral characterization of a collagenase-induced model of intracerebral haemorrhage in rats. J Neurosci Methods. 2010; 191:180-190.
22. Donatella DF, Merlini A, Laterza C, Martino G. Neural stem cell transplantation in central nervous system disorders: from cell replacement to neuroprotection. Curr Opin Neurol. 2012; 25(3):322-333.
23. Hagg T. From neurotransmitters to neurotrophic factors to neurogenesis. The Neuroscientist. 2009; 15(1):20-27. DOI: 10.1177/1073858408324789.
PMid:19218228 PMCid:PMC2722065
24. Matarredona ER, Talaverón R, Pastor AM. Interactions between neural progenitor cells and microglia in the subventricular zone: physiological implications in the neurogenic niche and after implantation in the injured brain. Front Cell Neurosci. 2018; 12:268. DOI: 10.3389/fncel.2018.00268.
PMid:30177874 PMCid:PMC6109750
25. Marques BL, Carvalho GA, Freitas EM, et al. The role of neurogenesis in neurorepair after ischemic stroke. 2018. Available from:

Zolotko K, Sukach О, Kompaniec А. The efficacy of fetal neural cell aggregates and their combination with fetal liver stromal cells to reduce brain damage after intracerebral hemorrhage in rats. Cell Organ Transpl. 2021; 9(1):22-28. doi:10.22494/cot.v9i1.118

Creative Commons License
Is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.