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This study evaluates the effect of autologous bone marrow stem cells infusion (ABMSCi) therapy for liver diseases.Treatment group will receive ABMSCi and drugs therapy ,while control group will only receive drugs therapy.
Autologous bone marrow stem cells (ABMSC) mobilization and harvest For harvesting more ABMSC, ABMSC mobilization is induced by recombinant human granulocyte colony stimulating factor (rhGCSF,Gran○R), administered subcutaneously at a dose of 300μg daily for three consecutive days before bone marrow puncture.
Bone marrow (160-200ml) of the patients is harvested from both posterior superior iliacs according to standard procedures under local anaesthesia and is collected in a plastic bag containing heparin.
Both treatment group and control group receive drugs therapy.
ABMSC separation and infusion ABMSC is separated and purified in a class 10,000 clean laboratory. After fat and bony particles are removed by filtration, collected cells are moved to a cell-processing device. The reagents adopt the method of negative cells collection. Take the cells which intended to remove as target cells, and carry out the removal step-by-step. On the basis of this method, red blood cells, blood platelets, blood plasma will be completely removed with part of white cells and lymphocytes being remarkably removed as well while all the stem cells / progenitor cells are being well retained.
The nucleated cell (white blood cell) count of final ABMSC is measured by an automated complete blood count instrument and flow cytometry analysis. The number of mononuclear cells is counted manually under a microscope by Wright-Giemsa stain method. Cell differentiation factor 34(CD34) positive cells were determined by flow cytometry analysis.
The time of ABMSC separation and purification is 2.5-3 hours. ABMSC is added to 10 ml saline and well mixed by shaking the vial gently. The catheter is pushed to reach the proper hepatic artery. The diameter of the catheter is 1.4mm, it is thin enough to easily been inserted to right gastric artery . The mixture of saline and ABMSC is infused into proper hepatic artery at uniform speed for about two minutes. The catheter is removed after the ABMSCi.
Statistical analysis - Categorical data are presented as absolute values and percentages, whereas continuous data are summarized as mean and Standard Deviation. Statistical analysis was performed using t-test for paired or unpaired samples. Time courses of measurements of liver function parameters were analyzed by repeated-measures ANOVA. The analysis is performed using the Statistic Package for Social Science (SPSS). All statistical analysis is based on two-tailed hypothesis tests with a significance level of p< 0.05.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| treatment group: ABMSCi & drugs | Experimental | ABMSCi: Autologous bone marrow stem cells infusion drugs such as Ursodeoxycholic Acid tablets(UDCA), each time 150 mg, three times a day orally |
|
| control group: drugs | Active Comparator | drugs such as Ursodeoxycholic Acid tablets(UDCA), each time 150 mg, three times a day orally |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Autologous bone marrow stem cells infusion | Procedure | Autologous bone marrow stem cells are infused into proper hepatic artery |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline alanine aminotransferase at 6 months | alanine aminotransferase (ALT) | baseline and 6 months after treatment |
| Change from baseline aspartate aminotransferase at 6 months | aspartate aminotransferase (AST) | baseline and 6 months after treatment |
| Change from baseline total bilirubin at 6 months | total bilirubin (TBil) | baseline and 6 months after treatment |
| Change from baseline direct bilirubin at 6 months | direct bilirubin (DBil) | baseline and 6 months after treatment |
| Change from baseline total bile acid at 6 months | total bile acid (TBA) | baseline and 6 months after treatment |
| Change from baseline albumin at 6 months | albumin (ALB) | baseline and 6 months after treatment |
| Change from baseline prothrombin time at 6 months | prothrombin time (PT), | baseline and 6 months after treatment |
| Change from baseline international normalized ratio at 6 months | international normalized ratio (INR) |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline liver density at 6 months | Low density, medium density, high density tested by abdominal B ultrasound/CT/MRI | baseline and 6 months after treatment |
| Change from baseline liver size at 6 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| yongping chen | Contact | 8613505777281 | 13505777281@163.com | |
| lanman xu | Contact | 8613587646315 | 13587646315@163.com |
| Name | Affiliation | Role |
|---|---|---|
| yongping chen | First Affiliated Hospital of Wenzhou Medical University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| the First Affiliated Hospital of Wenzhou Medical University | Recruiting | Wenzhou | Zhejiang | 325000 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25861263 | Background | Ma XR, Tang YL, Xuan M, Chang Z, Wang XY, Liang XH. Transplantation of autologous mesenchymal stem cells for end-stage liver cirrhosis: a meta-analysis based on seven controlled trials. Gastroenterol Res Pract. 2015;2015:908275. doi: 10.1155/2015/908275. Epub 2015 Mar 15. | |
| 24942592 | Result | Xu L, Gong Y, Wang B, Shi K, Hou Y, Wang L, Lin Z, Han Y, Lu L, Chen D, Lin X, Zeng Q, Feng W, Chen Y. Randomized trial of autologous bone marrow mesenchymal stem cells transplantation for hepatitis B virus cirrhosis: regulation of Treg/Th17 cells. J Gastroenterol Hepatol. 2014 Aug;29(8):1620-8. doi: 10.1111/jgh.12653. |
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| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| ID | Term |
|---|---|
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D014580 | Ursodeoxycholic Acid |
| ID | Term |
|---|---|
| D003840 | Deoxycholic Acid |
| D002793 | Cholic Acids |
| D001647 | Bile Acids and Salts |
| D013256 | Steroids |
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| drugs such as Ursodeoxycholic Acid tablets | Drug | Ursodeoxycholic Acid tablets(UDCA), each time 150 mg, three times a day orally |
|
|
| baseline and 6 months after treatment |
| Change from baseline white blood cell at 6 months | white blood cell (WBC) | baseline and 6 months after treatment |
| Change from baseline platelet at 6 months | platelet (PLT) | baseline and 6 months after treatment |
Enlarged size, normal size, shrunken size tested by abdominal B ultrasound/CT/MRI
| baseline and 6 months after treatment |
| Change from baseline spleen thickness at 6 months | tested by abdominal B ultrasound/CT/MRI | baseline and 6 months after treatment |
| Incidence of adverse events that are related to treatment | Postoperative pyrexia, infection, liver cirrhosis, ascites, upper gastrointestinal hemorrhage, malignant tumors of liver and other organs | baseline and 6 months after treatment |
| Number of participants that survive without developing disease | 12 months after treatment |
| Number of participants that survive with developing disease | 12 months after treatment |
| Number of participants that die after treatment | 12 months after treatment |
| 21608000 | Result | Peng L, Xie DY, Lin BL, Liu J, Zhu HP, Xie C, Zheng YB, Gao ZL. Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: short-term and long-term outcomes. Hepatology. 2011 Sep 2;54(3):820-8. doi: 10.1002/hep.24434. Epub 2011 Jul 14. |
| 26977164 | Result | Deng Q, Cai T, Zhang S, Hu A, Zhang X, Wang Y, Huang J. Autologous Peripheral Blood Stem Cell Transplantation Improves Portal Hemodynamics in Patients with Hepatitis B Virus-related Decompensated Cirrhosis. Hepat Mon. 2015 Dec 20;15(12):e32498. doi: 10.5812/hepatmon.32498. eCollection 2015 Dec. |
| 26659833 | Result | Mohamadnejad M, Vosough M, Moossavi S, Nikfam S, Mardpour S, Akhlaghpoor S, Ashrafi M, Azimian V, Jarughi N, Hosseini SE, Moeininia F, Bagheri M, Sharafkhah M, Aghdami N, Malekzadeh R, Baharvand H. Intraportal Infusion of Bone Marrow Mononuclear or CD133+ Cells in Patients With Decompensated Cirrhosis: A Double-Blind Randomized Controlled Trial. Stem Cells Transl Med. 2016 Jan;5(1):87-94. doi: 10.5966/sctm.2015-0004. Epub 2015 Dec 10. |
| 25445618 | Result | Chen Y, Chen S, Liu LY, Zou ZL, Cai YJ, Wang JG, Chen B, Xu LM, Lin Z, Wang XD, Chen YP. Mesenchymal stem cells ameliorate experimental autoimmune hepatitis by activation of the programmed death 1 pathway. Immunol Lett. 2014 Dec;162(2 Pt B):222-8. doi: 10.1016/j.imlet.2014.10.021. Epub 2014 Oct 28. |
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D002757 | Cholanes |