- Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China ;
Objective To investigate the clinical outlook of hepatic stem cells and its relations with liver cancer.
Methods The literatures of recent years on the studies of hepatic stem cells were reviewed.
Results Liver cancer may consist of cells of various differentiation grades and it may result from the perodifferentiated hepatic stem cells or abnormal differentiated cells.
Conclusion The hypothesis of hepatic stem cells has been identified extensively. Further study maybe helpful for revealing the origin, carcinogenesis of hepatic cancer, and may also be useful for the understanding of the mechanism of metastasis.
Citation： ZHOU Zhipeng,LI Bo. Research Progress and Clinical Value of Hepatic Stem Cells and Its Relations with Liver Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(4): 493-496. doi: Copy
| 1. | Wu XZ, Chen D. Origin of hepatocellular carcinoma: role of stem cells[J]. J Gastroenterol Hepatol, 2006; 21(7)∶1093. |
| 2. | Sharma AD, Cantz T, Manns MP, et al. The role of stem cells in physiology, pathophysiology, and therapy of the liver[J]. Stem Cell Rev, 2006; 2(1)∶51. |
| 3. | Weissman IL. Translating stem and progenitor cell biology to the clinic: barriers and opportunities[J]. Science， 2000; 287(5457)∶1442. |
| 4. | Suzuki A, Zheng YW, Fukao K, et al. Hepatic stem/progenitor cells with high proliferative potential in liver organ formation[J]. Transplant Proc, 2001; 33(1-2)∶585. |
| 5. | Ramiya VK, Maraist M, Arfors KE, et al. Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells[J]. Nat Med, 2000; 6(3)∶278. |
| 6. | 钟晓刚， 何生， 殷舞， 等. 成体肝干细胞向肝癌细胞趋向性迁移的体外实验[J]. 中华肝脏病杂志， 2005; 13(9)∶644. |
| 7. | Strick-Marchand H, Morosan S, Charneau P, et al. Bipotential mouse embryonic liver stem cell lines contribute to liver regeneration and differentiate as bile ducts and hepatocytes[J]. Proc Natl Acad Sci USA, 2004; 101(22)∶8360. |
| 8. | 金世龙， 刘宝华， 刘宏鸣， 等. 大鼠肝卵圆细胞的分离培养及干细胞标志分析[J]. 中国普外基础与临床杂志， 2007； 14（1）∶68 . |
| 9. | Zheng YW, Taniguchi H. Diversity of hepatic stem cells in the fetal and adult liver[J]. Semin Liver Dis, 2003; 23(4)∶337. |
| 10. | Paku S, Schnur J, Nagy P, et al. Origin and structural evolution of the early proliferating oval cells in rat liver[J]. Am J Pathol， 2001; 158(4)∶1313. |
| 11. | Haruna Y, Saito K, Spaulding S, et al. Identification of bipotential progenitor cells in human liver development[J]. Hepatology, 1996; 23(3)∶476. |
| 12. | Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells[J]. Science， 1999; 284(5417)∶1168. |
| 13. | Overturf K, al-Dhalimy M, Ou CN, et al. Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes[J]. Am J Pathol, 1997; 151(5)∶1273. |
| 14. | Block GD, Locker J, Bowen WC, et al. Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF/SF, EGF and TGF alpha in a chemically defined (HGM) medium[J]. J Cell Biol, 1996; 132(6)∶1133. |
| 15. | Sell S. Cellular origin of hepatocellular carcinomas[J]. Semin Cell Dev Biol, 2002; 13(6)∶419. |
| 16. | Alison MR, Poulsom R, Jeffery R, et al. Hepatocytes from non-hepatic adult stem cells[J]. Nature， 2000; 406(6793) ∶257. |
| 17. | Theise ND, Nimmakayalu M, Gardner R, et al. Liver from bone marrow in humans[J]. Hepatology, 2000; 32(1)∶11. |
| 18. | Lagasse E, Connors H, Al-Dhalimy M, et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo[J]. Nat Med, 2000; 6(11)∶1229. |
| 19. | Dabeva MD, Hwang SG, Vasa SR, et al. Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver[J]. Proc Natl Acad Sci USA， 1997; 94(14)∶7356. |
| 20. | Shen CN, Slack JM, Tosh D. Molecular basis of transdifferentiation of pancreas to liver[J]. Nat Cell Biol， 2000; 2(12)∶879. |
| 21. | Okumura K, Nakamura K, Hisatomi Y, et al. Salivary gland progenitor cells induced by duct ligation differentiate into hepatic and pancreatic lineages[J]. Hepatology， 2003; 38(1)∶104. |
| 22. | Petersen BE, Zajac VF, Michalopoulos GK. Hepatic oval cell activation in response to injury following chemically induced periportal or pericentral damage in rats[J]. Hepatology， 1998; 27(4)∶1030. |
| 23. | Liao JD, Zhang Y. Transdifferentiation of stem cell antigen-1 positive cells from murine fetal liver into renal cells: an experimental study[J]. Zhonghua Yi Xue Za Zhi， 2003; 83(19) ∶1686. |
| 24. | 廖继东， 张洹. 胎肝干细胞抗原阳性细胞向肾脏细胞分化的研究[J]. 中华医学杂志， 2003； 83（19）∶1686. |
| 25. | 王伟， 杨善民， 李新丰， 等. 肝癌及其癌前病变组织端粒酶活性检测的临床意义探讨[J]. 中国普外基础与临床杂志， 2000； 7（4）∶246. |
| 26. | Abelev GI, Eraiser TL. Cellular aspects of alpha-fetoprotein reexpression in tumors.[J]. Semin Cancer Biol, 1999; 9(2)∶95. |
| 27. | Ishikawa K, Sasaki A, Haraguchi N, et al. A case of an alpha-fetoprotein-producing intrahepatic cholangiocarcinoma suggests probable cancer stem cell origin[J]. Oncologist, 2007; 12(3)∶320. |
| 28. | Di Ilio C, Tiboni GM, Sacchetta P, et al. Time-dependent and tissue-specific variations of glutathione transferase activity during gestation in the mouse[J]. Mech Ageing Dev, 1995; 78(1)∶47 . |
| 29. | Chattopadhyay MB, CB MK, Kanna PS, et al. Combined supplementation of vanadium and beta-carotene suppresses placental glutathione S-transferase-positive foci and enhances antioxidant functions during the inhibition of diethylnitrosamine-induced rat liver carcinogenesis[J]. J Gastroenterol Hepatol, 2004; 19(6)∶683. |
| 30. | Huang T, Chesnokov V, Yokoyama KK, et al. Expression of the Hoxa-13 gene correlates to hepatitis B and C virus associated HCC[J]. Biochem Biophys Res Commun, 2001; 281(4) ∶1041. |
| 31. | Bucher NL, Farmer SR. Liver regeneration following partial hepatectomy: genes and metabolism [A]. In: Stain A, Deihl AM ed. Liver growth and repair [M]. London: Chapman and Hall, 1998∶1-27. |
| 32. | Thorgeirsson SS. Hepatic stem cells in liver regeneration[J]. FASEB J, 1996; 10(11)∶1249. |
| 33. | Sell S. Heterogeneity and plasticity of hepatocyte lineage cells[J]. Hepatology, 2001; 33(3)∶738. |
| 34. | Xiao JC, Jin XL, Ruck P, et al. Hepatic progenitor cells in human liver cirrhosis: immunohistochemical, electron microscopic and immunofluorencence confocal microscopic findings[J]. World J Gastroenterol, 2004; 10(8)∶1208. |
| 35. | Lowes KN, Brennan BA, Yeoh GC, et al. Oval cell numbers in human chronic liver diseases are directly related to disease severity[J]. Am J Pathol, 1999; 154(2)∶537. |
| 36. | Libbrecht L, Desmet V, Van Damme B, et al. Deep intralobular extension of human hepatic ‘progenitor cells’ correlates with parenchymal inflammation in chronic viral hepatitis: can ‘progenitor cells’ migrate?[J]. J Pathol, 2000; 192(3)∶373. |
| 37. | Crosby HA, Hubscher S, Fabris L, et al. Immunolocalization of putative human liver progenitor cells in livers from patients with end-stage primary biliary cirrhosis and sclerosing cholangitis using the monoclonal antibody OV-6[J]. Am J Pathol, 1998; 152(3)∶771. |
| 38. | Libbrecht L, De Vos R, Cassiman D, et al. Hepatic progenitor cells in hepatocellular adenomas[J]. Am J Surg Pathol, 2001; 25(11)∶1388. |
| 39. | 龚加庆， 方驰华， 李雅. 肝卵圆细胞在进行性肝损伤过程中分布及迁移的实验研究[J]. 中国普外基础与临床杂志， 2004； 11（5）∶389. |
| 40. | Choudhury S, Zhang R, Frenkel K, et al. Evidence of alterations in base excision repair of oxidative DNA damage during spontaneous hepatocarcinogenesis in Long Evans Cinnamon rats[J]. Cancer Res, 2003; 63(22)∶7704. |
| 41. | Takahashi H, Oyamada M, Fujimoto Y, et al. Elevation of serum alpha-fetoprotein and proliferation of oval cells in the livers of LEC rats[J]. Jpn J Cancer Res, 1988; 79(7)∶821. |
| 42. | Dumble ML, Croager EJ, Yeoh GC, et al. Generation and characterization of p53 null transformed hepatic progenitor cells: oval cells give rise to hepatocellular carcinoma[J]. Carcinogenesis, 2002; 23(3)∶435. |
| 43. | Tanaka S, Yamamoto T, Tanaka H, et al. Potentiality of combined hepatocellular and intrahepatic cholangiocellular carcinoma originating from a hepatic precursor cell: Immunohistochemical evidence[J]. Hepatol Res, 2005; 32(1)∶52. |
| 44. | Muraca M, Galbiati G, Vilei MT, et al. The future of stem cells in liver diseases[J]. Ann Hepatol， 2006; 5(2)∶68. |
| 45. | Shupe T, Petersen BE. Evidence regarding a stem cell origin of hepatocellular carcinoma[J]. Stem Cell Rev， 2005; 1(3)∶261. |
- 1. Wu XZ, Chen D. Origin of hepatocellular carcinoma: role of stem cells[J]. J Gastroenterol Hepatol, 2006; 21(7)∶1093.
- 2. Sharma AD, Cantz T, Manns MP, et al. The role of stem cells in physiology, pathophysiology, and therapy of the liver[J]. Stem Cell Rev, 2006; 2(1)∶51.
- 3. Weissman IL. Translating stem and progenitor cell biology to the clinic: barriers and opportunities[J]. Science， 2000; 287(5457)∶1442.
- 4. Suzuki A, Zheng YW, Fukao K, et al. Hepatic stem/progenitor cells with high proliferative potential in liver organ formation[J]. Transplant Proc, 2001; 33(1-2)∶585.
- 5. Ramiya VK, Maraist M, Arfors KE, et al. Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells[J]. Nat Med, 2000; 6(3)∶278.
- 6. 钟晓刚， 何生， 殷舞， 等. 成体肝干细胞向肝癌细胞趋向性迁移的体外实验[J]. 中华肝脏病杂志， 2005; 13(9)∶644.
- 7. Strick-Marchand H, Morosan S, Charneau P, et al. Bipotential mouse embryonic liver stem cell lines contribute to liver regeneration and differentiate as bile ducts and hepatocytes[J]. Proc Natl Acad Sci USA, 2004; 101(22)∶8360.
- 8. 金世龙， 刘宝华， 刘宏鸣， 等. 大鼠肝卵圆细胞的分离培养及干细胞标志分析[J]. 中国普外基础与临床杂志， 2007； 14（1）∶68 .
- 9. Zheng YW, Taniguchi H. Diversity of hepatic stem cells in the fetal and adult liver[J]. Semin Liver Dis, 2003; 23(4)∶337.
- 10. Paku S, Schnur J, Nagy P, et al. Origin and structural evolution of the early proliferating oval cells in rat liver[J]. Am J Pathol， 2001; 158(4)∶1313.
- 11. Haruna Y, Saito K, Spaulding S, et al. Identification of bipotential progenitor cells in human liver development[J]. Hepatology, 1996; 23(3)∶476.
- 12. Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells[J]. Science， 1999; 284(5417)∶1168.
- 13. Overturf K, al-Dhalimy M, Ou CN, et al. Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes[J]. Am J Pathol, 1997; 151(5)∶1273.
- 14. Block GD, Locker J, Bowen WC, et al. Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF/SF, EGF and TGF alpha in a chemically defined (HGM) medium[J]. J Cell Biol, 1996; 132(6)∶1133.
- 15. Sell S. Cellular origin of hepatocellular carcinomas[J]. Semin Cell Dev Biol, 2002; 13(6)∶419.
- 16. Alison MR, Poulsom R, Jeffery R, et al. Hepatocytes from non-hepatic adult stem cells[J]. Nature， 2000; 406(6793) ∶257.
- 17. Theise ND, Nimmakayalu M, Gardner R, et al. Liver from bone marrow in humans[J]. Hepatology, 2000; 32(1)∶11.
- 18. Lagasse E, Connors H, Al-Dhalimy M, et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo[J]. Nat Med, 2000; 6(11)∶1229.
- 19. Dabeva MD, Hwang SG, Vasa SR, et al. Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver[J]. Proc Natl Acad Sci USA， 1997; 94(14)∶7356.
- 20. Shen CN, Slack JM, Tosh D. Molecular basis of transdifferentiation of pancreas to liver[J]. Nat Cell Biol， 2000; 2(12)∶879.
- 21. Okumura K, Nakamura K, Hisatomi Y, et al. Salivary gland progenitor cells induced by duct ligation differentiate into hepatic and pancreatic lineages[J]. Hepatology， 2003; 38(1)∶104.
- 22. Petersen BE, Zajac VF, Michalopoulos GK. Hepatic oval cell activation in response to injury following chemically induced periportal or pericentral damage in rats[J]. Hepatology， 1998; 27(4)∶1030.
- 23. Liao JD, Zhang Y. Transdifferentiation of stem cell antigen-1 positive cells from murine fetal liver into renal cells: an experimental study[J]. Zhonghua Yi Xue Za Zhi， 2003; 83(19) ∶1686.
- 24. 廖继东， 张洹. 胎肝干细胞抗原阳性细胞向肾脏细胞分化的研究[J]. 中华医学杂志， 2003； 83（19）∶1686.
- 25. 王伟， 杨善民， 李新丰， 等. 肝癌及其癌前病变组织端粒酶活性检测的临床意义探讨[J]. 中国普外基础与临床杂志， 2000； 7（4）∶246.
- 26. Abelev GI, Eraiser TL. Cellular aspects of alpha-fetoprotein reexpression in tumors.[J]. Semin Cancer Biol, 1999; 9(2)∶95.
- 27. Ishikawa K, Sasaki A, Haraguchi N, et al. A case of an alpha-fetoprotein-producing intrahepatic cholangiocarcinoma suggests probable cancer stem cell origin[J]. Oncologist, 2007; 12(3)∶320.
- 28. Di Ilio C, Tiboni GM, Sacchetta P, et al. Time-dependent and tissue-specific variations of glutathione transferase activity during gestation in the mouse[J]. Mech Ageing Dev, 1995; 78(1)∶47 .
- 29. Chattopadhyay MB, CB MK, Kanna PS, et al. Combined supplementation of vanadium and beta-carotene suppresses placental glutathione S-transferase-positive foci and enhances antioxidant functions during the inhibition of diethylnitrosamine-induced rat liver carcinogenesis[J]. J Gastroenterol Hepatol, 2004; 19(6)∶683.
- 30. Huang T, Chesnokov V, Yokoyama KK, et al. Expression of the Hoxa-13 gene correlates to hepatitis B and C virus associated HCC[J]. Biochem Biophys Res Commun, 2001; 281(4) ∶1041.
- 31. Bucher NL, Farmer SR. Liver regeneration following partial hepatectomy: genes and metabolism [A]. In: Stain A, Deihl AM ed. Liver growth and repair [M]. London: Chapman and Hall, 1998∶1-27.
- 32. Thorgeirsson SS. Hepatic stem cells in liver regeneration[J]. FASEB J, 1996; 10(11)∶1249.
- 33. Sell S. Heterogeneity and plasticity of hepatocyte lineage cells[J]. Hepatology, 2001; 33(3)∶738.
- 34. Xiao JC, Jin XL, Ruck P, et al. Hepatic progenitor cells in human liver cirrhosis: immunohistochemical, electron microscopic and immunofluorencence confocal microscopic findings[J]. World J Gastroenterol, 2004; 10(8)∶1208.
- 35. Lowes KN, Brennan BA, Yeoh GC, et al. Oval cell numbers in human chronic liver diseases are directly related to disease severity[J]. Am J Pathol, 1999; 154(2)∶537.
- 36. Libbrecht L, Desmet V, Van Damme B, et al. Deep intralobular extension of human hepatic ‘progenitor cells’ correlates with parenchymal inflammation in chronic viral hepatitis: can ‘progenitor cells’ migrate?[J]. J Pathol, 2000; 192(3)∶373.
- 37. Crosby HA, Hubscher S, Fabris L, et al. Immunolocalization of putative human liver progenitor cells in livers from patients with end-stage primary biliary cirrhosis and sclerosing cholangitis using the monoclonal antibody OV-6[J]. Am J Pathol, 1998; 152(3)∶771.
- 38. Libbrecht L, De Vos R, Cassiman D, et al. Hepatic progenitor cells in hepatocellular adenomas[J]. Am J Surg Pathol, 2001; 25(11)∶1388.
- 39. 龚加庆， 方驰华， 李雅. 肝卵圆细胞在进行性肝损伤过程中分布及迁移的实验研究[J]. 中国普外基础与临床杂志， 2004； 11（5）∶389.
- 40. Choudhury S, Zhang R, Frenkel K, et al. Evidence of alterations in base excision repair of oxidative DNA damage during spontaneous hepatocarcinogenesis in Long Evans Cinnamon rats[J]. Cancer Res, 2003; 63(22)∶7704.
- 41. Takahashi H, Oyamada M, Fujimoto Y, et al. Elevation of serum alpha-fetoprotein and proliferation of oval cells in the livers of LEC rats[J]. Jpn J Cancer Res, 1988; 79(7)∶821.
- 42. Dumble ML, Croager EJ, Yeoh GC, et al. Generation and characterization of p53 null transformed hepatic progenitor cells: oval cells give rise to hepatocellular carcinoma[J]. Carcinogenesis, 2002; 23(3)∶435.
- 43. Tanaka S, Yamamoto T, Tanaka H, et al. Potentiality of combined hepatocellular and intrahepatic cholangiocellular carcinoma originating from a hepatic precursor cell: Immunohistochemical evidence[J]. Hepatol Res, 2005; 32(1)∶52.
- 44. Muraca M, Galbiati G, Vilei MT, et al. The future of stem cells in liver diseases[J]. Ann Hepatol， 2006; 5(2)∶68.
- 45. Shupe T, Petersen BE. Evidence regarding a stem cell origin of hepatocellular carcinoma[J]. Stem Cell Rev， 2005; 1(3)∶261.