The effectiveness of autologous mesenchymal stem cells in the treatment of liver cirrhosis and the method of their visualization in the patient’s body

2020 ◽  
Vol 22 (3) ◽  
pp. 35-40
Author(s):  
I. E. Kotkas ◽  
N. I. Enukashvili ◽  
Sh. M. Asadulayev ◽  
A. V. Chubar’
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Cell Therapy ◽  
Liver Tissue ◽  
Ultrasound Examination ◽  
Test Results ◽  
Resonance Imaging ◽  
Cell Structures ◽  
Autologous Mesenchymal Stem Cells

Abstract. The effectiveness of the influence of autologous mesenchymal stem cells on the function of liver tissue in liver cirrhosis of alimentary etiology is considered, as well as the possibility of visualization of the introduced cell structures with subsequent cytological confirmation. To be able to track autologous mesenchymal stem cells introduced in the patients body, they were labeled with iron oxide nanoparticles. Visualization of the introduced cell structures was performed using magnetic resonance imaging and ultrasound examination of the liver. 6 months after the cell therapy, clinical and biochemical blood tests, lidocaine test results, elastography indicators were evaluated, and the dynamics of hepatic encephalopathy was evaluated. The effectiveness of using autologous mesenchymal stem cells was evidenced by the improvement of the above indicators. Also, 6 months after treatment, a liver tissue biopsy was performed from the sites of fixation of previously introduced cell structures. Histological examination revealed the largest number of labeled cells in the liver micro-nodes, as well as at the borders of micro-nodes and fibrous septa. The use of cell therapy in a patient suffering from liver cirrhosis of alimentary etiology helped to improve the indicators of laboratory and instrumental research methods. No complications were detected during the procedure.

scholarly journals Autologous mesenchymal stem cells in treatment of liver cirrhosis: evaluation of effectiveness and visualization method

2020 ◽  
Vol 5 (3) ◽  
pp. 197-203
Author(s):  
Inna E. Kotkas ◽  
Natella I. Enukashvili ◽  
Shamil M. Asadulayev ◽  
Anna V. Chubar
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Cell Therapy ◽  
Clinical Observation ◽  
Health Assessment ◽  
Subjective Health ◽  
Oxide Nanoparticles ◽  
Cell Structures ◽  
Autologous Mesenchymal Stem Cells

Through clinical observation, we present an assessment of the autologous mesenchymal stem cells effectiveness in treatment of liver cirrhosis of alimentary etiology. In order to determine the localization of the implanted cell structures, the stem cells were previously labeled with iron (II, III) oxide nanoparticles (IONPs). Further MRI visualization helped to detect the cell structures stained with iron oxide nanoparticles in the human body. In 6 months after the cell therapy, the patient underwent clinical and biochemical blood tests, MEGX test, elastography and subjective health assessment test. The tests data analysis revealed the improvement of the values of all examined parameters after the cell treatment. Also in 6 and 12 months after the treatment, a liver biopsy was performed from the area where the implanted stem cells were visualized. In histological examination of liver bioptates obtained from the area of MSC transplantation, the largest number of stained cells was observed in liver micronodes, as well as at the boundaries of micronodes and fibrous septa. A portion of the bioptate obtained in 12 months after transplantation was used to produce primary cell cultures. Before the first re-seeding of the cultures, cell colonies of both fibroblast-like morphology and epithelial were detected in them. Both types of colonies contained the particles. Conducting the cell therapy to a patient with liver cirrhosis of alimentary etiology contributed to improving the laboratory and instrumental examinations indicators. The patient had come through the treatment procedure satisfactorily, no complications were registered.

The use of autologous mesenchymal stem cells to improve the functional state of the liver after its resection (clinical observation)

2020 ◽  
pp. 6-13
Author(s):  
I. E. Kotkas ◽  
V. P. Zemlyanoi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Resection ◽  
Protein Function ◽  
Clinical Observation ◽  
Liver Volume ◽  
Resonance Imaging ◽  
Results Of Treatment ◽  
Cell Structures ◽  
Autologous Mesenchymal Stem Cells

The article provides a clinical observation with an assessment of biochemical indicators and changes in liver volume in the patient after liver resection. A peculiarity of this clinical observation is that intraoperative (during liver resection) administration of autologous mesenchymal stem cells was performed on this patient. In the postoperative period, the patient was not given protein and hepatotropic preparations. As a result of the use of cellular technologies, on the 15th day after the operation, the patient recovered protein function of the liver; 10 days after the operation, the level of prothrombin time and transaminases normalized; on day 5 after the operation, alkaline phosphatase and GGTP were normalized. Previously, we proved that autologous mesenchymal stem cells introduced through the portal vein of the liver are fixed directly in the liver tissue. These results were confirmed by magnetic resonance imaging. The introduced cell structures were visualized by pre-labeling them with iron oxide nanoparticles. The search for new ways to restore liver function after resections is a significant task in liver surgery, which in the future will help to improve the postoperative results of treatment of patients and reduce the bed-day.

scholarly journals Evaluation of the Possibility of Fixation of Autologous Mesenchymal Stem Cells in Liver Tissue Introduced into the Portal Vein of the Liver in a Patient Suffering from Cirrhosis

2021 ◽  
Vol 14 (2) ◽  
pp. 136-139
Author(s):  
Inna Evgenievna Kotkas ◽  
Shamil Magomedovich Asadulaev ◽  
Natella Iosifovna Enukashvili
Keyword(s):  
Magnetic Resonance Imaging ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Magnetic Resonance ◽  
Portal Vein ◽  
Human Body ◽  
Resonance Imaging ◽  
Abdominal Organs ◽  
Autologous Mesenchymal Stem Cells

To date, there are quite a large number of reports of the use of stem cells in the treatment of various diseases in humans. However, the authors do not provide credible evidence that the introduced stem cells come directly into the target organ. Without a clear understanding of the location of the introduced stem cells, it is difficult to reliably assess the effect of their use. The article gives its own observation about the possibility of imaging in the human body autologous mesenchymal stem cells introduced through the portal vein of the liver to a patient suffering from cirrhosis. Iron oxide nanoparticles were used as labels. A rather simple question was previously solved: how to create a label of such size that the viability of the stem cell was preserved and it could be visualized in the human body when performing magnetic resonance imaging of abdominal organs. Following in vitro studies, the most appropriate stem cell marking embodiment was chosen to provide both adequate imaging and cell viability. After administration of marked table cells, magnetic resonance imaging of abdominal organs was performed to the patient. The introduced stem cells were visualised only in hepatic tissue. According to clinical and biochemical blood tests - no deviations were detected. There were no complications against the background of this procedure. The patient was discharged for outpatient treatment in satisfactory condition.

scholarly journals Mesenchymal Stem Cells in the Adult Human Liver: Hype or Hope?

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1127 ◽  
Author(s):  
Irina V. Kholodenko ◽  
Leonid K. Kurbatov ◽  
Roman V. Kholodenko ◽  
Garik V. Manukyan ◽  
Konstantin N. Yarygin
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Liver Tissue ◽  
Liver Diseases ◽  
Human Liver ◽  
Chronic Liver ◽  
Attractive Alternative ◽  
Short Supply

Chronic liver diseases constitute a significant economic, social, and biomedical burden. Among commonly adopted approaches, only organ transplantation can radically help patients with end-stage liver pathologies. Cell therapy with hepatocytes as a treatment for chronic liver disease has demonstrated promising results. However, quality human hepatocytes are in short supply. Stem/progenitor cells capable of differentiating into functionally active hepatocytes provide an attractive alternative approach to cell therapy for liver diseases, as well as to liver-tissue engineering, drug screening, and basic research. The application of methods generally used to isolate mesenchymal stem cells (MSCs) and maintain them in culture to human liver tissue provides cells, designated here as liver MSCs. They have much in common with MSCs from other tissues, but differ in two aspects—expression of a range of hepatocyte-specific genes and, possibly, inherent commitment to hepatogenic differentiation. The aim of this review is to analyze data regarding liver MSCs, probably another type of liver stem/progenitor cells different from hepatic stellate cells or so-called hepatic progenitor cells. The review presents an analysis of the phenotypic characteristics of liver MSCs, their differentiation and therapeutic potential, methods for isolating these cells from human liver, and discusses issues of their origin and heterogeneity. Human liver MSCs are a fascinating object of fundamental research with a potential for important practical applications.

The Use of Autologous Mesenchymal Stem Cells for Cell Therapy of Patients with Amyotrophic Lateral Sclerosis in Belarus

2015 ◽  
Vol 159 (4) ◽  
pp. 576-581 ◽  
Author(s):  
Yu. N. Rushkevich ◽  
S. M. Kosmacheva ◽  
G. V. Zabrodets ◽  
S. I. Ignatenko ◽  
N. V. Goncharova ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amyotrophic Lateral Sclerosis ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Autologous Mesenchymal Stem Cells ◽  
Lateral Sclerosis

scholarly journals Functional properties of mesenchymal multipotent stromal stem cells obtained from bone marrow of patients with liver cirrhosis

2014 ◽  
Vol 95 (5) ◽  
pp. 669-674
Author(s):  
B A Agaev ◽  
R M Agaev ◽  
A G Popandopulo ◽  
R E Dzhafarli
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Functional Properties ◽  
Primary Cultures ◽  
Small Cells ◽  
Viral Etiology ◽  
Phenotypic Properties ◽  
Autologous Mesenchymal Stem Cells

Aim. To study of the functional properties of autologous mesenchymal multipotent stem cells in patients with cirrhosis of different etiologies. Methods. Studied were the functional and phenotypic properties of autologous mesenchymal stem cells derived from the bone marrow in 35 patients (26 men and 9 women) with cirrhosis of the liver at the age of 19-53 years. Among the patients studied viral etiology was diagnosed in 18 (51.4%), alcohol - in 13 (37.1%), autoimmune - in 4 (11.4%) patients with liver cirrhosis. Results. Autologous mesenchymal stem cells from all of the observed patients were able to divide. The highest yield and the doubling rate of cell populations were observed in patients with viral cirrhosis. Comparative morphometric study of primary cultures derived stem cells in patients with autoimmune and alcoholic hepatitis, showed the presence of relatively small cells (less than 20 microns), which make up about 30% of the total number of cells. At the same time, in bone marrow derived cell cultures of patients with viral etiology of the disease the number of small cells was 1.5 times greater which makes approximately 49% of the total cell population. The vast majority of cultured stem cells, regardless of the etiology of cirrhosis express specific for these cells «stromal» markers - CD73, CD90 and CD105. Autologous mesenchymal stem cells isolated from bone marrow of patients with alcoholic liver cirrhosis characterized by the most pronounced pro-inflammatory, immunoregulatory potential. Conclusion. Functional and phenotypic properties of autologous mesenchymal stem cells in various forms of cirrhosis are different which requires adequate cultivation and correction before their transplantation.

scholarly journals Enhanced therapeutic effects of umbilical cord mesenchymal stem cells after prolonged treatment for HBV- related liver failure and liver cirrhosis

2020 ◽  
Author(s):  
Yifan Jia ◽  
Xin Shu ◽  
Xiaoan Yang ◽  
Haixia sun ◽  
Huijuan Cao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Stem Cell ◽  
Cell Therapy ◽  
Liver Failure ◽  
Stem Cell Therapy ◽  
Prolonged Treatment ◽  
Therapeutic Effects ◽  
Failure Group

Abstract Background: This study aimed to investigate the therapeutic effect of umbilical cord mesenchymal stem cells (UCMSCs) on HBV-related liver failure and liver cirrhosis and to compare the different efficacies of UCMSCs after different treatment courses.Methods: This was an observational study that retrospectively considered a three-year period during which 513 patients who received stem cell infusion met the criteria of hepatic failure and liver cirrhosis were identified from databases of the Third Affiliated Hospital of Sun Yat-sen University. Eligible patients were categorized into the liver failure group and liver cirrhosis group. The two groups were divided into different subgroups according to the times of stem cell therapy. In the liver failure group, group A received more than 4 weeks and group B received less than 4 weeks. In the liver cirrhosis group, patients who received more than 4 weeks of stem cell therapy belonged to group C, and group D received less than 4 weeks. The patients were followed up for 24 weeks. The demographics, clinical characteristics, biochemical factors, and MELD scores were recorded and compared among different groups.Results: A total of 64 patients met the criteria of liver failure, and 59 patients met the criteria of liver cirrhosis. After UCMSC treatments, the levels of ALT, AST, and TBIL at all postbaseline time points were significantly lower than those at baseline in the liver failure group and liver cirrhosis group; the PTA and MELD scores only gradually improved in the liver failure group. Four weeks after UCMSC treatment, patients with prolonged treatment with UCMSCs had higher TBIL decline levels than patients who terminated treatment with UCMSCs. After more than 4 weeks of UCMSC treatment, there was no statistically significant difference in the levels of change for ALT, AST, TBIL, PTA value and the MELD score between patients with liver failure with prolonged treatment with UCMSCs and patients with liver cirrhosis with prolonged treatment with UCMSCs at all observation weeks. However, the median decline and cumulative decline in the TBIL level of patients with liver failure with a standard 4-week treatment course were higher than those of patients with liver cirrhosis with a standard 4-week treatment course.Conclusion: Peripheral infusion of UCMSCs showed good therapeutic effects for HBV-related liver failure and liver cirrhosis. Prolonging the treatment course can increase the curative effect of UCMSCs for end-stage liver disease, especially for patients with cirrhosis.

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