USING OF MSC WITH DIFFERENT ONTOGENETIC MATURITY FOR CORRECTION OF CHRONIC FIBROSING LIVER DAMAGE
https://doi.org/10.15825/1995-1191-2013-3-73-82
Abstract
Aim. To compare the effectiveness of MSC with different degree of ontogenetic maturity (MSC bone marrow – MSC BM and MSC umbilical cord – MSC UC) on regenerative processes in injured liver. Methods. In 4 groups of experiments on Wistar rats (n = 80) with a model of fibrotic toxic liver damage (FLD) it was studied the effect of MSCs with different degree of ontogenetic maturity on recovery processes at the regeneration of damaged liver: 1 gr. – Control, 2 gr. and 3 gr. introduction of MSC BM, included in Sphero®GEL-long in doses of 2.5 ×106 and 5.0 x 106 cells, respectively, and 4 gr. – introduction of MSC UC in the form of cell-spheroids (8–10 × 105 cells). The cells were injected into the damaged liver in 7 days after the end of FDL-modeling. The effect of cell therapy was studied during 180 days. The effectiveness of corrective therapy was evaluated by the results of functional and morphological investigations of livers (histological control of parenchymal and nonparenchy- mal liver tissue). Results. MSC BM in both doses and MSC UC contributed to a more rapid normalization of liver enzyme indices compared with the control (1 gr.), but the differences in the rate of recovery of disturbed enzymatic liver functions between groups 2, 3 and 4 – were absent. In 90 days after the cell application it was determined a more pronounced recovery activity of cells in groups 3 and 4; in 180 days the more pronounced activation of recovery processes was observed in group 3; but in group 4 the sclerotic processes were more pro- nounced in this period. Conclusion. For the induction of recovery processes in damage liver it is advisable not to use the MSC UC, but to use MSC BM in the Sphero®GEL, because MSC BM exert not only local but also systemic immune-regulatory effect, increasing the pool of T-reg. cells, which are additional carriers of regenera- tion information in organism.
About the Authors
M. Y. Shagidulin
Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs (Head – academician of RAMSci, prof. S.V. Gautier), Moscow, Russian Federation
Department of Transplantology and Artificial Organs I.M. Setchenov First Moscow State Medical University (rector – korresponding member of RAMSci, prof. P.V. Glybochko), Moscow, Russian Federation
Russian Federation
Russian Federation
A. A. Gorkun
The Institute of General Pathology and Pathophysiology RAMSci (Head – аcademician,
prof. A.A. Kubatiev), Moscow, Russian Federation
Russian Federation
Russian Federation
N. A. Onishchenko
Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs (Head – academician of RAMSci, prof. S.V. Gautier), Moscow, Russian Federation
Department of Transplantology and Artificial Organs I.M. Setchenov First Moscow State Medical University (rector – korresponding member of RAMSci, prof. P.V. Glybochko), Moscow, Russian Federation
Russian Federation
Russian Federation
M. E. Krasheninnikov
Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs (Head – academician of RAMSci, prof. S.V. Gautier), Moscow, Russian Federation
Russian Federation
Russian Federation
I. M. Iljinsky
Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs (Head – academician of RAMSci, prof. S.V. Gautier), Moscow, Russian Federation
Department of Transplantology and Artificial Organs I.M. Setchenov First Moscow State Medical University (rector – korresponding member of RAMSci, prof. P.V. Glybochko), Moscow, Russian Federation
Russian Federation
Russian Federation
N. P. Mogeiko
Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs (Head – academician of RAMSci, prof. S.V. Gautier), Moscow, Russian Federation
Russian Federation
Russian Federation
L. V. Bashkina
Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs (Head – academician of RAMSci, prof. S.V. Gautier), Moscow, Russian Federation
Russian Federation
Russian Federation
I. N. Saburina
The Institute of General Pathology and Pathophysiology RAMSci (Head – аcademician,
prof. A.A. Kubatiev), Moscow, Russian Federation
Russian Federation
Russian Federation
V. I. Sevastjanov
Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs (Head – academician of RAMSci, prof. S.V. Gautier), Moscow, Russian Federation
Russian Federation
Russian Federation
S. V. Gautier
Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs (Head – academician of RAMSci, prof. S.V. Gautier), Moscow, Russian Federation
Department of Transplantology and Artificial Organs I.M. Setchenov First Moscow State Medical University (rector – korresponding member of RAMSci, prof. P.V. Glybochko), Moscow, Russian Federation
Russian Federation
Russian Federation
References
1. Onishchenko N.A., Lyundup A.V., Shagidulin M.Y., Kra- sheninnikov M.E. The sinusoidal cells of the liver and bone marrow cells as a single functional component re- gulatory system reductive morphogenesis in a healthy and damaged liver. Klet. transpl. and tkan. inzheneriya. 2011; VI (2): 73–87 (in rus).
2. Kuharchyk A.L. Stem cells and regenerative-plastic me- dicine. Transplantologiya. 2004; 7 (3): 76–90 (in rus).
3. Lundup А.V., Оnischenko N.А., Shagidulin М.Y., Кra- sheninnikov М.Е. Stem/progenitor cells of liver and bone marrow as regulators of a reparative regeneration of da- maged liver. Vestnik transplantologii i iskusstvennyh or- ganov. 2010; XII (2): 100–107 (in rus).
4. Fang B., Shi M., Liao L., Yang S., Liu Y., Zhao R.C. Systemic infusion of FLK1+ mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice. Transplant. 2004; 78: 83–88.
5. Chernyh E.R., Ostanin A.A., Palcev A.I. Stem cells in liver regeneration: new approaches for treatment liver failure. Hepatologiya. 2004; 5: 24–33 (in rus).
6. Jiang Y., Jahagirdar B.N., Reinhardt R.L., Schwartz R.E., Keene C.D., Ortiz-Gonzalez X.R., Reyes M., Lenvik T., Lund T., Blackstad M., Du J., Aldrich S., Lisberg A., Low W.C., Largaespada D.A., Verfaillie C.M. Pluripo- tency of mesenchimal stem cells derived from adult mar- row. Nature. 2002; 418: 41–49.
7. Schwartz R.E., Reyes M., Koodie J., Jiang Y., Black- stad M., Lund T., Lenvik T., Johnson S., Hu W.S., Ver- faillie C.M. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J. Clin. Ivest. 2002; 109: 1291–1302.
8. Terada N., Hamazaki T., Oka M., Hoki M., Masta- lerz D.M., Nakano Y., Meyer E.M., Morel L., Pe- tersen B.E., Scott E.W. Bone marrow cells adopt the phe- notype of other cells by spontaneous cell fusion. Nature. 2002; 416: 542–545.
9. Onishchenko N.A., Lyundup A.V., Gazizov I.M., Deev R.V., Shagidulin M.Y., Avramov P.V. Two-phase dy- namics of fibrolytic effect of bone marrow multipotent mesenchymal stromal cells (MSC) in chronic fibrotic liver damage. Vestnik transplantologii i iskusstvennyh organov. 2011; XIII (3): 51–58 (in rus).
10. Shumakov V.I., Krasheninnikov M.E., Onishchenko N.A., Bystrov V.A., Brill A.G., Abalmasov K.G. Cell culture, comprising osteogenic precursor cells, the implant based on it and use it to restore the integrity of the bone. Patent number 2240135. from 20.11.2004 (in rus).
11. Gautier S.V., Shagidulin M.Y., Onishchenko N.A., Kra- sheninnikov M.E., Sevastiyanov V.I. The method and graft for treating hepatic insufficiency. Patent number 2010110063/14 (014141). from 03.03.2011 (in rus).
12. Dai L.J., Li H.Y., Guan L.X., Ritchie G., Zhou J.X. The therapeutic potential of bone marrow-derived mesenchy- mal stem cells on hepatic cirrhosis. Stem Cell Res. 2009; 2 (1): 16–25.
13. TeraiS.,IshikawaT.,OmoriK.,AoyamaK.,MarumotoY., Urata Y., Yokoyama Y., Uchida K., Yamasaki T., Fujii Y., Okita K., Sakaida I. Improved liver function in patients with liver cirrhosis after autologous bone marrow cell in- fusion therapy. Stem Cells. 2006; 24 (10): 2292–2298.
14. Kiyasov A.P., Odintsov A.H., Gumerova A.A., Gazi- zov I.M., Farrahov A.Z., Kundakchyan G.G., Abdulha- kov S.R., Cheremina N.A., Yilmaz T.S. Transplantation of autologous hematopoietic stem cell patients with chronic hepatitis. Klet. transpl. and tkan. inzheneriya. 2008; 3 (1): 70–75 (in rus).
15. Gasbarrini A., Rapaccini G.L., Rutella S., Zocco M.A., Tittoto P., Leone G., Pola P., Gasbarrini G., Di Cam- pli C. Rescue therapy by portal infusion of autologous stem cells in a case of drug-induced hepatitis. Dig. Liver Dis. 2007; 39: 878–882.
16. Esch J.S. 2nd, Knoefel W.T., Klein M., Ghodsizad A., Fuerst G., Poll L.W., Piechaczek C., Burchardt E.R., Feifel N., Stoldt V., Stockschläder M., Stoecklein N., Tustas R.Y., Eisenberger C.F., Peiper M., Häussinger D., Hosch S.B. Portal application of autologous CD133+ bone marrow cells to the liver: a novel concept to support hepatic regeneration. Stem Cells. 2005; 23: 463–470.
17. Shumakov V.I., Onishchenko N.A. Biological reserves of bone marrow cells and correction of organ dysfunctions. Monograph. M.: Lavr, 2009: 307 (in rus).
Review
For citations:
Shagidulin M.Y., Gorkun A.A., Onishchenko N.A., Krasheninnikov M.E., Iljinsky I.M., Mogeiko N.P., Bashkina L.V., Saburina I.N., Sevastjanov V.I., Gautier S.V. USING OF MSC WITH DIFFERENT ONTOGENETIC MATURITY FOR CORRECTION OF CHRONIC FIBROSING LIVER DAMAGE. Russian Journal of Transplantology and Artificial Organs. 2013;15(3):73-82. (In Russ.) https://doi.org/10.15825/1995-1191-2013-3-73-82
Views:
1419
Email this article 