Volodina 2014 Abstract MiP2014
|Multipotent stromal cells injection improves rat liver regeneration through activation of mitochondrial functions after subtotal hepatectomy.|
Mammalian liver has unique regenerative capacity, which makes liver resection useful research on regeneration and ways to accelerate regenerative processes. The aim of our work was to study mitochondrial function in rat liver tissue after subtotal hepatectomy and to investigate effects of multipotent stromal cells (MSCs) injection on liver regeneration.
On day 0 we performed a 80% hepatectomy on adult white male rats. Liver mitochondria were isolated from dissected liver tissue. On day 7 we performed total hepatectomy and isolated liver mitochondria under the same experimental conditions; after that animals were sacrificed. Rats were divided into two groups: control (N=12); MSCs (N=9). On day 0 animals of MSCs group were subjected to intrasplenic injection of 106 MSC in saline. Rats of the control group were injected with the same volume of saline. MSCs were isolated from rats’ umbilical cord by enzyme digestion, cultured in appropriate growth medium and rats’ phenotype characterized in accordance with a standard protocol. Mitochondrial respiratory parameters were measured using an oxygraph (Hansatech, UK).
At the end of the experiment, seven and six rats had survived in control and MSCs groups, respectively. Only mitochondria isolated from these rats were taken into account for the final analysis. A decreased mitochondrial protein amount to liver tissue weight ratio was observed on day 7, compared to day 0, in both groups. In the MSCs group the decrease of mitochondrial protein concentration was significantly less than in the control group (MSCs: 1.5±0.2 fold; control: 2.1±0.3 fold). At the same time the ~P/O ratio did not change in the control group (day 0: 3.0±0.4; day 7: 3.0±0.3) but slightly (P<0.1) increased in the MSCs group (day 0: 2.7±0.3; day 7: 3.2±0.1). Mitochondrial oxygen flux (nmol O2∙min-1∙mg-1 protein) in the control group significantly increased on day 7 compared to day 0 in the presence of glutamate+malate (CIL: 5.2±0.4 vs 3.0±0.2), +rotenone+succinate+ADP (CIIP: 53.9±1.7 vs 34.7±5.2), +oligomycin (CIIL: 9.9±0.7 vs 7.2±0.9), and +FCCP (CIIE: 53.7±4.5 vs 43.0±3.7). No increase in respiration was found in the MSCs group. L/E and P/E coupling control ratios for CII-linked respiration were unchanged in both groups.
In summary, we can assume that MSCs injection accelerates not only proliferation and liver growth but also differentiation of progenitors to different cell types, through normalization of liver mitochondrial function in terms of correlation between respiration, Δψmt and ROS production, in rat liver tissue after 80% liver resection.
Labels: MiParea: Respiration
Stress:Oxidative stress;RONS Organism: Rat Tissue;cell: Liver Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS, ET Pathway: N, NS
Event: B1, Oral MiP2014
1-VI Kulakov Research Center Obstetrics, Gynecology, Perinatology, Ministry Health Russian Fed; 2-Research Inst Human Morphology, Russian Acad Med Sc; 3-AN Belozersky Physico-Chem Biol Inst, Moscow State Univ; Moscow, Russia. – [email protected]
Supported by grant RFBR № 14-04-01224 А.