The influence of the ratio of liver cells and bone marrow in the implantable cell-engineering structures of the liver on the recovery efficiency of functional and morphological parameters in chronic liver failure

Author:

Shagidulin M. Yu.1,Onishchenko N. A.2,Krasheninnikov M. E.3,Nikolskaya A. O.2,Volkova E. A.2,Iljinsky I. M.2,Mogeiko N. P.2,Sevastianov V. I.2,Gautier S. V.1

Affiliation:

1. V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs of the Ministry of Healthcare of the Russian Federation; I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of the Russian Federation (Sechenovsky University)

2. V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs of the Ministry of Healthcare of the Russian Federation

3. I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of the Russian Federation (Sechenovsky University)

Abstract

Aim:to determinate the most effective liver cells and multipotent mesenchymal stromal cells of bone marrow (MMSC BM) ratio into implantable cell engineering constructions (CECs) used for chronic liver failure (CLF) correcting.Materials and methods.For creating liver CECs it was used a biopolymer implant – a composition of a heterogeneous collagen-containing gel (BMCG) (Sphero®GEL trademark) containing viable liver cells and MMSC BM in the following ratios – 1 : 1; 5 : 1 and 10 : 1 respectively. CECs with different ratios of liver cells and MMSC BM were implanted into liver of rats in which chronic liver failure (CLF), was modeled by using CCl4. The effectiveness of the regulatory effects of CECs (with different cell ratios) on regenerative processes in livers were assessed by using biochemical, morphological and morphometric methods at different periods after their implantation.Results.Corrective effect of CECs with different cell composition on biochemical and morphological parameters of livers at chronic liver failure was established. During studying the liver CECs with various cell ratios of liver cells and MMSC BM (1 : 1; 5 : 1 and 10 : 1 respectively), it was found that the most optimal ratio of cells into the CECs is 5 : 1, because at this ratio of cells, there were a more distinct normalization of the morphological and functional liver parameters within 365 days after modeling CLF and maintenance of the structural homeostasis into the CECs. Themselves, which allows predicting their long-term regulatory effect on the liver tissue in CLF and maintaining its normal structural and functional state.Conclusion.The effective correction of chronic liver failure can be carried out by using the implanted liver CECs, in which donor liver cells and MMSC BM where presented in ratios – 1 : 1; 5 : 1 and 10 : 1. But analysis of prolonged correction of liver morphological and functional parameters at CECs using it was allow to recommend the preferences using of CECs with ratio 5 : 1, because prolonged preservation of structural homeostasis into these CECs makes possible to prognosticate their prolonged regulatory action on the liver tissue at CLF, especially for recipients on a waiting list for liver transplantation.

Publisher

V.I. Shimakov Federal Research Center of Transplantology and Artificial Organs

Subject

Transplantation,Immunology and Allergy

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