Do multipotent mesenchymal stromal cells differentiate into hepatocytes?

Current Opinion in Organ Transplantation

Volumn 12, Issue 6, 2007, Pages 668-672

  Gonelle Gispert, Carmen ^a   Baertschiger, Reto ^a   Morel, Philippe ^a   Bühler, Leo ^a  

^a GENEVA UNIVERSITY HOSPITALS   (Switzerland)

Author keywords

Differentiation; Hepatocyte; Liver regeneration; Multipotent mesenchymal stromal cells

Indexed keywords

BONE MARROW CELL; CELL DIFFERENTIATION; CELL LINE; CELL TRANSPLANTATION; ECTODERM; ENDODERM; GENE EXPRESSION; HEMATOPOIETIC STEM CELL; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LIVER CELL; LIVER DISEASE; LIVER FAILURE; LIVER REGENERATION; MESENCHYME CELL; MULTIPOTENT STEM CELL; NONHUMAN; REVIEW;

EID: 36248997549     PISSN: 10872418     EISSN: 15317013     Source Type: Journal    
DOI: 10.1097/MOT.0b013e3282f19f0f     Document Type: Review

References (55)

1. Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells. Science 1999; 284:1168-1170.
2. Alison MR, Poulsom R, Jeffery R, et al. Hepatocytes from non-hepatic adult stem cells. Nature 2000; 406:257.
3. Theise ND, Nimmakayalu M, Gardner R, et al. Liver from bone marrow in humans. Hepatology 2000; 32:11-16.
4. Nguyen TH, Ferry N. Liver gene therapy: advances and hurdles. Gene Ther 2004; 11 (Suppl 1):S76-S84.
5. Thorgeirsson SS, Grisham JW. Overview of recent experimental studies on liver stem cells. Semin Liver Dis 2003; 23:303-312.
6. Dahlke MH, Popp FC, Bahlmann FH, et al. Liver regeneration in a retrorsine/CCl4-induced acute liver failure model: do bone marrow-derived cells contribute? J Hepatol 2003; 39:365-373.
7. Kanazawa Y, Verma IM. Little evidence of bone marrow-derived hepatocytes in the replacement of injured liver. Proc Natl Acad Sci U S A 2003; 100 (Suppl 1):11850-11853.
8. Wu T, Cieply K, Nalesnik MA, et al. Minimal evidence of transdifferentiation from recipient bone marrow to parenchymal cells in regenerating and long-surviving human allografts. Am J Transplant 2003; 3:1173-1181.
9. Lagasse E, Connors H, Al-Dhalimy M, et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 2000; 6:1229-1234.
10. Wang X, Ge S, McNamara G, et al. 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; 101:4201-4208.
11. Wang X, Montini E, Al-Dhalimy M, et al. Kinetics of liver repopulation after bone marrow transplantation. Am J Pathol 2002; 161:565-574.
12. Wang X, Al-Dhalimy M, Lagasse E, et al. Liver repopulation and correction of metabolic liver disease by transplanted adult mouse pancreatic cells. Am J Pathol 2001; 158:571-579.
13. Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 2002; 297:2256-2259.
14. Vassilopoulos G, Wang PR, Russell DW. Transplanted bone marrow regenerates liver by cell fusion. Nature 2003; 422:901-904.
15. Wang X, Willenbring H, Akkari Y, et al. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 2003; 422:897-901.
16. Willenbring H, Bailey AS, Foster M, et al. Myelomonocytic cells are sufficient for therapeutic cell fusion in liver. Nat Med 2004; 10:744-748.
17. Khurana S, Mukhopadhyay A. Characterization of the potential subpopulation of bone marrow cells involved in the repair of injured liver tissue. Stem Cells 2007; 25:1439-1447. This study showed that liver injury stimulated hematopoietic progenitor cell proliferation and mobilization into peripheral blood.
18. Thorgeirsson SS, Grisham JW. Hematopoietic cells as hepatocyte stem cells: a critical review of the evidence. Hepatology 2006; 43:2-8.
19. Friedenstein AJ, Gorskaja JF, Kulagina NN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol 1976; 4:267-274.
20. Owen M, Friedenstein AJ. Stromal stem cells: marrow-derived osteogenic precursors. Ciba Found Symp 1988; 136:42-60.
21. Deldar A, Lewis H, Weiss L. Bone lining cells and hematopoiesis: an electron microscopic study of canine bone marrow. Anat Rec 1985; 213:187-201.
22. Muguruma Y, Yahata T, Miyatake H, et al. Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment. Blood 2006; 107:1878-1887.
23. Dexter TM, Allen TD, Lajtha LG. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol 1977; 91:335-344.
24. Horwitz EM, Le Blanc K, Dominici M, et al. Clarification of the nomenclature for MSC: the International Society for Cellular Therapy position statement. Cytotherapy 2005; 7:393-395.
25. Campagnoli C, Roberts IA, Kumar S, et al. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 2001; 98:2396-2402.
26. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997; 276:71-74.
27. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284:143-147.
28. Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002; 13:4279-4295.
29. Seeberger KL, Dufour JM, Shapiro AM, et al. Expansion of mesenchymal stem cells from human pancreatic ductal epithelium. Lab Invest 2006; 86:141-153.
30. Sudo K, Kanno M, Miharada K, et al. Mesenchymal progenitors able to differentiate into osteogenic, chondrogenic, and/or adipogenic cells in vitro are present in most primary fibroblast-like cell populations. Stem Cells 2007; 25:1610-1617.
31. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8:315-317.
32. Buhring HJ, Battula VL, Treml S, et al. Novel markers for the prospective isolation of human MSC. Ann N Y Acad Sci 2007; 1106:262-271.
33. Martinez C, Hofmann TJ, Marino R, et al. Human bone marrow mesenchymal stromal cells express the neural ganglioside GD2: a novel surface marker for the identification of MSCs. Blood 2007; 109:4245-4248. A brief report in which investigators demonstrated that neural ganglioside (GD2) was expressed on bone marrow and adipose tissue-derived MSCs but not on foreskin fibroblasts or bone marrow specimens. Expression level of GD2 remained similar during expansion and should therefore be used to study MSC biology.
34. Francois S, Bensidhoum M, Mouiseddine M, et al. Local irradiation not only induces homing of human mesenchymal stem cells at exposed sites but promotes their widespread engraftment to multiple organs: a study of their quantitative distribution after irradiation damage. Stem Cells 2006; 24:1020-1029.
35. Devine SM, Cobbs C, Jennings M, et al. Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood 2003; 101:2999-3001.
36. Eckfeldt CE, Mendenhall EM, Verfaillie CM. The molecular repertoire of the 'almighty' stem cell. Nat Rev Mol Cell Biol 2005; 6:726-737.
37. Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418:41-49.
38. Schwartz RE, Reyes M, Koodie L, et al. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest 2002; 109:1291-1302.
39. Lee KD, Kuo TK, Whang-Peng J, et al. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 2004; 40:1275-1284.
40. Lee OK, Kuo TK, Chen WM, et al. Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 2004; 103:1669-1675.
41. Avital I, Inderbitzin D, Aoki T, et al. Isolation, characterization, and transplantation of bone marrow-derived hepatocyte stem cells. Biochem Biophys Res Commun 2001; 288:156-164.
42. Hong H, Chen JZ, Zhou F, et al. Influence of serum from liver-damaged rats on differentiation tendency of bone marrow-derived stem cells. World J Gastroenterol 2004; 10:2250-2253.
43. Jang YY, Collector MI, Baylin SB, et al. Hematopoietic stem cells convert into liver cells within days without fusion. Nat Cell Biol 2004; 6:532-539.
44. Rai RM, Yang SQ, McClain C, et al. Kupffer cell depletion by gadolinium chloride enhances liver regeneration after partial hepatectomy in rats. Am J Physiol 1996; 270 (6 Pt 1):G909-G918.
45. Ong SY, Dai H, Leong KW. Hepatic differentiation potential of commercially available human mesenchymal stem cells. Tissue Eng 2006; 12:3477-3485.
46. Lange C, Bassler P, Lioznov MV, et al. Liver-specific gene expression in mesenchymal stem cells is induced by liver cells. World J Gastroenterol 2005; 11:4497-4504.
47. Lange C, Bassler P, Lioznov MV, et al. Hepatocytic gene expression in cultured rat mesenchymal stem cells. Transplant Proc 2005; 37:276-279.
48. Sato Y, Araki H, Kato J, et al. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood 2005; 106:756-763.
49. Aurich I, Mueller LP, Aurich H, et al. Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers. Gut 2007; 56:405-415. These investigators showed that human MSCs expressed hepatocyte-specific genes and proteins in specific conditions. They demonstrated that preconditioned MSCs delivered into livers by intrasplenic injections in Pfp/Rag2 mice engrafted in periportal regions. Antibodies specific against human albumin and HepPar1 allowed detection of MSCs in the liver. Specificity of such staining needs to be confirmed by labelling MSCs prior to injection.
50. Popp FC, Slowik P, Eggenhofer E, et al. No contribution of multipotent mesenchymal stromal cells to liver regeneration in a rat model of prolonged hepatic injury. Stem Cells 2007; 25:639-645. A negative study which showed that in an animal model of hepatic injury, transplantation of rat hepatocytes resulted in stable engraftment, however rat MSCs were not able to engraft or differentiate into hepatocytes.
51. Schrepfer S, Deuse T, Reichenspurner H, et al. Stem cell transplantation: the lung barrier. Transplant Proc 2007; 39:573-576.
52. Oyagi S, Hirose M, Kojima M, et al. Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats. J Hepatol 2006; 44:742-748.
53. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006; 98:1076-1084.
54. Yu Y, Yao AH, Chen N, et al. Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration. Mol Ther 2007; 15:1382-1389. This study shows that HGF-expressing MSC transplantation improved liver regeneration after small-for-seize transplantation in rats and provided evidence that HGF-expressing MSCs had antiapoptotic and mitogenic effects on hepatocytes in the early phase of liver regeneration. MSCs were found in the recipient liver with few cells expressing albumin. The investigators suggested that genetically modified HGF-expressing MSCs represent a novel therapeutic strategy to regulate liver graft regeneration.
55. Russo FP, Alison MR, Bigger BW, et al. The bone marrow functionally contributes to liver fibrosis. Gastroenterology 2006; 130:1807-1821.