Umbilical cord mesenchymal stem cells with bone marrow stem cells in the treatment of decompensated cirrhosis: a 1-year follow-up study

doi:10.3969/j.issn.2095-4344.2015.10.011

Abstract

Abstract:

BACKGROUND: There are most single-center studies about bone marrow stem cells applied to treat decompensated cirrhosis, but the therapeutic results are not ideal. It is possibly related to aging, physical weakness, poor bone marrow hematopoietic function, less available number of stem cells and feeble ability of regeneration and proliferation in liver cirrhosis patients. Umbilical cord mesenchymal stem cells are characterized of easy to obtain, wide source and weak immunogenicity. Co-transplantation of bone marrow stem cells and umbilical cord mesenchymal stem cells may improve the therapeutic effects on decompensated cirrhosis patients.

OBJECTIVE: To investigate the efficacy and safety of co-transplantation of umbilical cord mesenchymal stem cells and bone marrow stem cells on decompensated cirrhosis.

METHODS: Thirty-two decompensated cirrhosis patients were randomly divided into two groups: in stem cell group, 13 patients received co-transplantation of umbilical cord mesenchymal stem cells and bone marrow stem cells based on regular medical treatment; in control group, 19 patients only underwent the regular medical treatment. All the patients were follow-up for 1 year. Alanine aminotransferase, albumin, total bilirubin, prothrombin time, Child-Pugh score and Model for End-Stage Liver Disease score, 1-year survival rate, Quality of Life score and adverse reactions related to stem cell therapy were observed and recorded in the two groups at 4, 12, 52 weeks after treatment.

RESULTS AND CONCLUSION: At 4, 12, 52 weeks after treatment, improvements in the liver function, prothrombin time, Child-Pugh score and Model for End-Stage Liver Disease score were found in the two groups, but there was no difference between the two groups (P > 0.05). At 4 weeks after transplantation, the clinical symptoms and Quality of Life score in the stem cell group were significantly improved, which were better than those in the control group (P < 0.05). But at 12 and 52 weeks after treatment, no difference was found between the two groups (P > 0.05). In addition, the 1-year survival rate showed no difference between the two groups, and no severe adverse reactions related to stem cell therapy occurred during the follow-up. Co-transplantation of umbilical cord mesenchymal stem cells and bone marrow stem cells is safe and effective to improve the clinical symptoms of decompensated cirrhosis patients. However, further studies with larger samples are warranted to better clarify the co-transplantation effects.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

全文链接：

Key words: Umbilical Cord, Mesenchymal Stem Cell Transplantation, Myeloid Progenitor Cells, Liver Cirrhosis, Treatment Outcome

CLC Number:

R394.2

Zeng Zhi-yu, Li Dong-liang, Fang Jian, Ruan Mei, Xia Lei, Zhang Zhi-qiang, Zhang Shi-an. Umbilical cord mesenchymal stem cells with bone marrow stem cells in the treatment of decompensated cirrhosis: a 1-year follow-up study[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(10): 1533-1538.

Figures/Tables 7

References

[1]Gordon MY, Levicar N, Pai M, et al. Characterization and clinical application of human CD34+ stem/progenitor cell populations mobilized into the blood by granulocyte colony-stimulating factor.Stem Cells. 2006;24(7):1822-1830.
[2]Mohamadnejad M, Alimoghaddam K, Mohyeddin-Bonab M, et al. Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis.Arch Iran Med. 2007;10(4):459-466.
[3]Liao X, AnCheng JY, Zhou QJ, et al.Therapeutic effect of autologous bone marrow-derived liver stem cells transplantation in hepatitis B virus-induced liver cirrhosis. Hepatogastroenterology. 2013;60(123):406-409.
[4]Han Y, Yan L, Han G, et al.Controlled trials in hepatitis B virus-related decompensate liver cirrhosis: peripheral blood monocyte transplant versus granulocyte-colony-stimulating factor mobilization therapy.Cytotherapy. 2008;10(4):390-396.
[5]Zhang Z, Lin H, Shi M, et al. Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroenterol Hepatol. 2012;27 Suppl 2:112-120.
[6]Zoulim F, Radenne S, Ducerf C. Management of patients with decompensated hepatitis B virus associated [corrected] cirrhosis. Liver Transpl. 2008;14 Suppl 2:S1-7.
[7]Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells.Science. 1999;284(5411):143-147.
[8]Petersen BE, Bowen WC, Patrene KD,et al.Bone marrow as a potential source of hepatic oval cells. Science. 1999;284 (5417): 1168-1170.
[9]Theise ND, Nimmakayalu M, Gardner R, et al. Liver from bone marrow in humans. Hepatology. 2000;32(1):11-16.
[10]Terai S, Sakaida I, Yamamoto N, et al. An in vivo model for monitoring trans-differentiation of bone marrow cells into functional hepatocytes.J Biochem. 2003;134(4):551-558.
[11]范敬静,李东良,何秀华,等. 骨髓间充质干细胞向肝样细胞的诱导及分化[J].中国组织工程研究与临床康复,2011,15(14): 2491-2494.
[12]Li DL, He XH, Zhang SA, et al. Bone marrow-derived mesenchymal stem cells promote hepatic regeneration after partial hepatectomy in rats. Pathobiology. 2013; 80(5):228- 234.
[13]何秀华,李东良,江军,等.移植途径对大鼠骨髓间充质干细胞归巢及肝功能恢复的影响[J].中华细胞与干细胞杂志:电子版,2011, 1(1): 57-62.
[14]李东良,何秀华,范敬静,等.骨髓动员与骨髓间充质干细胞移植促进极量肝切除大鼠肝再生作用的对照研究[J].解放军医学杂志, 2014,39(8):595-600.
[15]Chen H,Zhang Y,Yang ZJ,et al.Human umbilical cord Wharton’s jelly-derived oligodendrocyte precursor-like cells for axon and myelin sheath regeneration.Neural Regen Res. 2013;8(10): 890-899.
[16]van Poll D, Parekkadan B, Cho CH, et al. Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo.Hepatology. 2008;47(5): 1634-1643.
[17]Mohamadnejad M, Alimoghaddam K, Bagheri M, et al. Randomized placebo-controlled trial of mesenchymal stem cell transplantation in decompensated cirrhosis. Liver Int. 2013;33(10):1490-1496.