Differentiation of Human Umbilical Cord Blood Stem Cells into Hepatocytes in Vivo and in Vitro

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2006 Jul 1

PMID 16810750

Citations 11

Authors

Xiao-Peng Tang

Min Zhang

Xu Yang

Li-Min Chen

Yang Zeng

Affiliations

Soon will be listed here.

Abstract

Aim: To study the condition and potentiality of human umbilical cord blood stem cells (HUCBSC) to differentiate into hepatocytes in vivo or in vitro.

Methods: In a cell culture study of human umbilical cord blood stem cell (HUCBSC) differentiation, human umbilical cord blood mononuclear cells (HUCBMNC) were separated by density gradient centrifugation. Fibroblast growth factor (FGF) and hepatocyte growth factor (HGF) and the supernatant of fetal liver were added in the inducing groups. Only FGF was added in the control group. The expansion and differentiation of HUCBMNC in each group were observed. Human alpha fetoprotein (AFP) and albumin (ALB) were detected by immunohistochemistry. In the animal experiments, the survival SD rats with acute hepatic injury after carbon tetrachloride (CCL4) injection 48 h were randomly divided into three groups. The rats in group A were treated with human umbilical cord blood serum. The rats in group B were treated with HUCBMNC transplantation. The rats in group C were treated with HUCBMNC transplantation followed by intraperitoneal cyclophosphamide for 7 d. The rats were killed at different time points after the treatment and the liver tissue was histopathologically studied and human AFP and ALB detected by immunohistochemistry. The human X inactive-specific transcript gene fragment in the liver tissue was amplified by PCR to find human DNA.

Results: The results of cell culture showed that adherent cells were stained negative for AFP or ALB in control group. However, the adherent cells in the inducing groups stained positive for AFP or ALB. The result of animal experiment showed that no human AFP or ALB positive cells present in the liver tissue of group A (control group). However, many human AFP or ALB positive cells were scattered around sinus hepaticus and the central veins of hepatic lobules and in the portal area in group B and group C after one month. The fragment of human X chromagene could be detected in the liver tissue of groups B and C, but not in group A.

Conclusion: Under certain conditions HUCBSC can differentiate into liver cells in vivo and in vitro.

Citing Articles

Liver Regeneration by Hematopoietic Stem Cells: Have We Reached the End of the Road?.

Siapati E, Roubelakis M, Vassilopoulos G Cells. 2022; 11(15).

PMID: 35954155 PMC: 9367594. DOI: 10.3390/cells11152312.

DNA barcode to trace the development and differentiation of cord blood stem cells (Review).

Wang M, Zhou Y, Lai G, Huang Q, Cai W, Han Z Mol Med Rep. 2021; 24(6).

PMID: 34643250 PMC: 8524429. DOI: 10.3892/mmr.2021.12489.

Application of Cord Blood and Cord Blood-Derived Induced Pluripotent Stem Cells for Cartilage Regeneration.

Rim Y, Nam Y, Ju J Cell Transplant. 2018; 28(5):529-537.

PMID: 30251563 PMC: 7103603. DOI: 10.1177/0963689718794864.

Comparative analysis of human UCB and adipose tissue derived mesenchymal stem cells for their differentiation potential into brown and white adipocytes.

Rashnonejad A, Ercan G, Gunduz C, Akdemir A, Tiftikcioglu Y Mol Biol Rep. 2018; 45(3):233-244.

PMID: 29453764 DOI: 10.1007/s11033-018-4156-1.

Effect of human umbilical cord blood stem cell transplantation on oval cell response in 2-AAF/CCL4 liver injury model: experimental immunohistochemical study.

Abdellatif H, Shiha G, Saleh D, Eltahry H, Botros K Inflamm Regen. 2017; 37:5.

PMID: 29259704 PMC: 5725643. DOI: 10.1186/s41232-017-0035-8.

References

Newsome P, Johannessen I, Boyle S, Dalakas E, McAulay K, Samuel K . Human cord blood-derived cells can differentiate into hepatocytes in the mouse liver with no evidence of cellular fusion. Gastroenterology. 2003; 124(7):1891-900. DOI: 10.1016/s0016-5085(03)00401-3. View

Wang Y, Nan X, Li Y, Zhang R, Yue W, Yan F . Induction of umbilical cord blood-derived beta2m-c-Met+ cells into hepatocyte-like cells by coculture with CFSC/HGF cells. Liver Transpl. 2005; 11(6):635-43. DOI: 10.1002/lt.20419. View

Lee O, Kuo T, Chen W, Lee K, Hsieh S, Chen T . Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood. 2003; 103(5):1669-75. DOI: 10.1182/blood-2003-05-1670. View

Rocha V, Wagner Jr J, Sobocinski K, Klein J, Zhang M, Horowitz M . Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources. N Engl J Med. 2000; 342(25):1846-54. DOI: 10.1056/NEJM200006223422501. View

Alison M, Poulsom R, Jeffery R, Dhillon A, Quaglia A, Jacob J . Hepatocytes from non-hepatic adult stem cells. Nature. 2000; 406(6793):257. DOI: 10.1038/35018642. View

Lagasse E, CONNORS H, Reitsma M, Dohse M, Osborne L, Wang X . Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med. 2000; 6(11):1229-34. DOI: 10.1038/81326. View

Brazelton T, Rossi F, Keshet G, Blau H . From marrow to brain: expression of neuronal phenotypes in adult mice. Science. 2000; 290(5497):1775-9. DOI: 10.1126/science.290.5497.1775. View

Rocha V, Cornish J, Sievers E, Filipovich A, Locatelli F, Peters C . Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood. 2001; 97(10):2962-71. DOI: 10.1182/blood.v97.10.2962. View

Avital I, Inderbitzin D, Aoki T, Tyan D, Cohen A, Ferraresso C . Isolation, characterization, and transplantation of bone marrow-derived hepatocyte stem cells. Biochem Biophys Res Commun. 2001; 288(1):156-64. DOI: 10.1006/bbrc.2001.5712. View

10.

Buzanska L, Machaj E, ZABLOCKA B, Pojda Z, Domanska-Janik K . Human cord blood-derived cells attain neuronal and glial features in vitro. J Cell Sci. 2002; 115(Pt 10):2131-8. DOI: 10.1242/jcs.115.10.2131. View

11.

Schwartz R, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T . Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest. 2002; 109(10):1291-302. PMC: 150983. DOI: 10.1172/JCI15182. View

12.

Fiegel H, Lioznov M, Cortes-Dericks L, Lange C, Kluth D, Fehse B . Liver-specific gene expression in cultured human hematopoietic stem cells. Stem Cells. 2003; 21(1):98-104. DOI: 10.1634/stemcells.21-1-98. View

13.

Broxmeyer H, Srour E, Hangoc G, Cooper S, Anderson S, Bodine D . High-efficiency recovery of functional hematopoietic progenitor and stem cells from human cord blood cryopreserved for 15 years. Proc Natl Acad Sci U S A. 2003; 100(2):645-50. PMC: 141050. DOI: 10.1073/pnas.0237086100. View

14.

Kakinuma S, Tanaka Y, Chinzei R, Watanabe M, Shimizu-Saito K, Hara Y . Human umbilical cord blood as a source of transplantable hepatic progenitor cells. Stem Cells. 2003; 21(2):217-27. DOI: 10.1634/stemcells.21-2-217. View

15.

Wang X, Ge S, McNamara G, Hao Q, Crooks G, Nolta J . Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human hematopoietic stem cells. Blood. 2003; 101(10):4201-8. PMC: 3781008. DOI: 10.1182/blood-2002-05-1338. View

16.

Di Campli C, Piscaglia A, Pierelli L, Rutella S, Bonanno G, Alison M . A human umbilical cord stem cell rescue therapy in a murine model of toxic liver injury. Dig Liver Dis. 2004; 36(9):603-13. DOI: 10.1016/j.dld.2004.03.017. View

17.

Almeida-Porada G, Porada C, Chamberlain J, Torabi A, Zanjani E . Formation of human hepatocytes by human hematopoietic stem cells in sheep. Blood. 2004; 104(8):2582-90. DOI: 10.1182/blood-2004-01-0259. View

18.

Tanabe Y, Tajima F, Nakamura Y, Shibasaki E, Wakejima M, Shimomura T . Analyses to clarify rich fractions in hepatic progenitor cells from human umbilical cord blood and cell fusion. Biochem Biophys Res Commun. 2004; 324(2):711-8. DOI: 10.1016/j.bbrc.2004.09.115. View

19.

Petersen B, BOWEN W, Patrene K, Mars W, Sullivan A, Murase N . Bone marrow as a potential source of hepatic oval cells. Science. 1999; 284(5417):1168-70. DOI: 10.1126/science.284.5417.1168. View

20.

Kim D, Fujiki Y, Fukushima T, Ema H, Shibuya A, Nakauchi H . Comparison of hematopoietic activities of human bone marrow and umbilical cord blood CD34 positive and negative cells. Stem Cells. 1999; 17(5):286-94. DOI: 10.1002/stem.170286. View