Application of autologous multipotent mesenchymal stromal cells for correction of liver function in patients suffering from alcoholic liver cirrhosis

2020 ◽  
Vol 22 (4) ◽  
pp. 33-36
Author(s):  
I. E. Kotkas ◽  
V. I. Masurov ◽  
I. G. Bakulin ◽  
N. I. Enukashvili ◽  
Sh. M. Asadulayev

Clinical experience of application of autologous multipotent mesenchymal stromal cells in treatment of patient suffering from liver cirrhosis of alcoholic etiology is presented. A special feature is that the hepatocyte precursors were isolated directly from the patients liver tissue. The patient underwent laparoscopic surgery to obtain the largest volume of material and to be able to visually control the tissue sampling with minimal fibrotic changes. After liver tissue sampling, the patient was discharged for outpatient treatment in a satisfactory condition. Subsequently, the patient was re-admitted to the hospital. During repeated hospitalization, multipotent mesenchymal stromal cells in the amount of 20 million were injected into the arterial bed of the liver using x-ray endovascular technique. In the control study, 6 months after treatment, according to the 13C-metacetin test, normalization of liver function, regression of portal hypertension, and an increase in platelet levels were noted. There were no complications during this treatment. Treatment of patients suffering from cirrhosis of the liver is quite a serious and complex task. As a rule, the patient learns about his diagnosis already in the presence of complications, when the liver function is already significantly impaired. The propensity of the population to alcoholism leads to the formation of fibrosis, and subsequently cirrhosis of the liver. The absence of anti-fibrotic drugs contributes to the implementation of research to find alternative methods of treatment for this category of patients. In General, the use of autologous multipotent mesenchymal stromal cells is an effective and promising method, and research in this direction should be continued.

2020 ◽  
Vol 37 (1) ◽  
pp. 430-441
Author(s):  
Alexander Rühle ◽  
Andreas Thomsen ◽  
Rainer Saffrich ◽  
Maren Voglstätter ◽  
Birgit Bieber ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diego Noé Rodríguez-Sánchez ◽  
Giovana Boff Araujo Pinto ◽  
Luciana Politti Cartarozzi ◽  
Alexandre Leite Rodrigues de Oliveira ◽  
Ana Livia Carvalho Bovolato ◽  
...  

Abstract Background Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration. Methods 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL + MSCs (NGC multi-functionalized with 106 canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve. Results The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair. Conclusions 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.


2019 ◽  
Vol 60 (8) ◽  
pp. 2042-2049
Author(s):  
Irina N. Shipounova ◽  
Nataliya A. Petinati ◽  
Alexey E. Bigildeev ◽  
Tamara V. Sorokina ◽  
Larisa A. Kuzmina ◽  
...  

2010 ◽  
Vol 11 (1) ◽  
pp. 11 ◽  
Author(s):  
Christina Holzwarth ◽  
Martin Vaegler ◽  
Friederike Gieseke ◽  
Stefan M Pfister ◽  
Rupert Handgretinger ◽  
...  

2018 ◽  
Vol 28 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Diego Noé Rodríguez Sánchez ◽  
Luiz Antonio de Lima Resende ◽  
Giovana Boff Araujo Pinto ◽  
Ana Lívia de Carvalho Bovolato ◽  
Fábio Sossai Possebon ◽  
...  

Crush injuries in peripheral nerves are frequent and induce long-term disability with motor and sensory deficits. Due to axonal and myelin sheath disruptions, strategies for optimized axonal regeneration are needed. Multipotent mesenchymal stromal cells (MSC) are promising because of their anti-inflammatory properties and secretion of neurotrophins. The present study investigated the effect of canine adipose tissue MSC (Ad-MSC) transplantation in an experimental sciatic nerve crush injury. Wistar rats were divided into three groups: sham ( n = 8); Crush+PBS ( n = 8); Crush+MSC ( n = 8). Measurements of sciatic nerve functional index (SFI), muscle mass, and electromyography (EMG) were performed. Canine Ad-MSC showed mesodermal characteristics (CD34-, CD45-, CD44+, CD90+ and CD105+) and multipotentiality due to chondrogenic, adipogenic, and osteogenic differentiation. SFI during weeks 3 and 4 was significantly higher in the Crush+MSC group ( p < 0.001). During week 4, the EMG latency in the Crush+MSC groups had better near normality ( p < 0.05). The EMG amplitude showed results close to normality during week 4 in the Crush+MSC group ( p < 0.04). There were no statistical differences in muscle weight between the groups ( p > 0.05), but there was a tendency toward weight gain in the Crush+MSC groups. Better motor functional recovery after crush and perineural canine Ad-MSC transplantation was observed during week 2. This was maintained till week 4. In conclusion, the canine Ad-MSC transplantation showed early pro-regenerative effects between 2–4 weeks in the rat model of sciatic nerve crush injury.


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