Adipose tissue‐derived mesenchymal stem cells as a source of human hepatocytes

Recent observations indicate that several stem cells can differentiate into hepatocytes; thus, cell‐based therapy is a potential alternative to liver transplantation. The goal of the present study was to examine the in vitro hepatic differentiation potential of adipose tissue‐derived mesenchymal stem cells (AT‐MSCs). We used AT‐MSCs from different age patients and found that, after incubation with specific growth factors (hepatocyte growth factor [HGF], fibroblast growth factor [FGF1], FGF4) the CD105+ fraction of AT‐MSCs exhibited high hepatic differentiation ability in an adherent monoculture condition. CD105+ AT‐MSC‐derived hepatocyte‐like cells revealed several liver‐specific markers and functions, such as albumin production, low‐density lipoprotein uptake, and ammonia detoxification. More importantly, CD105+ AT‐MSC‐derived hepatocyte‐like cells, after transplantation into mice incorporated into the parenchyma of the liver. Conclusion: Adipose tissue is a source of multipotent stem cells that can be easily isolated, selected, and induced into mature, transplantable hepatocytes. The fact that they are easy to procure ex vivo in large numbers makes them an attractive tool for clinical studies in the context of establishing an alternative therapy for liver dysfunction. (HEPATOLOGY 2007;46:219–228.)

[1]  A. Bayés‐Genís,et al.  Effect of aging on the pluripotential capacity of human CD105+ mesenchymal stem cells , 2006, European journal of heart failure.

[2]  Kam W Leong,et al.  Inducing hepatic differentiation of human mesenchymal stem cells in pellet culture. , 2006, Biomaterials.

[3]  Meir Liebergall,et al.  Osteogenic Differentiation of Noncultured Immunoisolated Bone Marrow‐Derived CD105+ Cells , 2006, Stem cells.

[4]  S. Forbes,et al.  The bone marrow functionally contributes to liver fibrosis. , 2006, Gastroenterology.

[5]  Hermann Eichler,et al.  Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue , 2006, Stem cells.

[6]  K. Timper,et al.  Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. , 2006, Biochemical and biophysical research communications.

[7]  F. Guilak,et al.  Clonal analysis of the differentiation potential of human adipose‐derived adult stem cells , 2006, Journal of cellular physiology.

[8]  N. Benvenisty,et al.  Study of hepatocyte differentiation using embryonic stem cells , 2005, Journal of cellular biochemistry.

[9]  W. Ansorge,et al.  Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. , 2005, Experimental hematology.

[10]  G. Im,et al.  Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells? , 2005, Osteoarthritis and cartilage.

[11]  T. Ochiya,et al.  Recapitulation of in vivo gene expression during hepatic differentiation from murine embryonic stem cells , 2005, Hepatology.

[12]  M. Hedrick,et al.  Multipotential differentiation of adipose tissue-derived stem cells. , 2005, The Keio journal of medicine.

[13]  P. Arner,et al.  Functional studies of mesenchymal stem cells derived from adult human adipose tissue. , 2005, Experimental cell research.

[14]  W. Chiu,et al.  Isolation and Characterization of Neurogenic Mesenchymal Stem Cells in Human Scalp Tissue , 2005, Stem cells.

[15]  T. Shen,et al.  [Identification of human bone marrow mesenchymal stem cells: preparation and utilization of two monoclonal antibodies against SH2, SH3]. , 2005, Zhongguo shi yan xue ye xue za zhi.

[16]  Q. Han,et al.  Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo. , 2005, Biochemical and biophysical research communications.

[17]  S. Hwang,et al.  In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells. , 2005, Biochemical and biophysical research communications.

[18]  S. Gauer,et al.  Epithelial differentiation of human adipose tissue-derived adult stem cells. , 2005, Biochemical and biophysical research communications.

[19]  T. Ochiya,et al.  Direct hepatic fate specification from mouse embryonic stem cells , 2005, Hepatology.

[20]  Min-Jeong Seo,et al.  Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. , 2005, Biochemical and biophysical research communications.

[21]  P. Collas,et al.  Isolation and transcription profiling of purified uncultured human stromal stem cells: alteration of gene expression after in vitro cell culture. , 2005, Molecular biology of the cell.

[22]  Sunil S Tholpady,et al.  Cell Surface and Transcriptional Characterization of Human Adipose‐Derived Adherent Stromal (hADAS) Cells , 2005, Stem cells.

[23]  F. Claas,et al.  Isolation of Mesenchymal Stem Cells of Fetal or Maternal Origin from Human Placenta , 2004, Stem cells.

[24]  Y. Bae,et al.  Characterization and Expression Analysis of Mesenchymal Stem Cells from Human Bone Marrow and Adipose Tissue , 2004, Cellular Physiology and Biochemistry.

[25]  H. Klüter,et al.  Critical Parameters for the Isolation of Mesenchymal Stem Cells from Umbilical Cord Blood , 2004, Stem cells.

[26]  C. Dani,et al.  Adipocyte differentiation of multipotent cells established from human adipose tissue. , 2004, Biochemical and biophysical research communications.

[27]  Min Zhu,et al.  Comparison of Multi-Lineage Cells from Human Adipose Tissue and Bone Marrow , 2003, Cells Tissues Organs.

[28]  T. Ochiya,et al.  Differentiation of embryonic stem cells into hepatocytes: Biological functions and therapeutic application , 2003, Hepatology.

[29]  Min Zhu,et al.  Human adipose tissue is a source of multipotent stem cells. , 2002, Molecular biology of the cell.

[30]  W. Wilkison,et al.  Neurogenic differentiation of murine and human adipose-derived stromal cells. , 2002, Biochemical and biophysical research communications.

[31]  R. Schwartz,et al.  Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. , 2002, The Journal of clinical investigation.

[32]  N. Fisk,et al.  Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. , 2001, Blood.

[33]  J. Gimble,et al.  Surface protein characterization of human adipose tissue‐derived stromal cells , 2001, Journal of cellular physiology.

[34]  H. Lorenz,et al.  Multilineage cells from human adipose tissue: implications for cell-based therapies. , 2001, Tissue engineering.

[35]  E A Morris,et al.  Isolation, characterization, and chondrogenic potential of human bone marrow‐derived multipotential stromal cells , 2000, Journal of cellular physiology.

[36]  W. Janssen,et al.  Adult Bone Marrow Stromal Cells Differentiate into Neural Cells in Vitro , 2000, Experimental Neurology.

[37]  Sunil Badve,et al.  Derivation of hepatocytes from bone marrow cells in mice after radiation‐induced myeloablation , 2000, Hepatology.

[38]  W. Mars,et al.  Bone marrow as a potential source of hepatic oval cells. , 1999, Science.

[39]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[40]  G Cossu,et al.  Muscle regeneration by bone marrow-derived myogenic progenitors. , 1998, Science.

[41]  W. Killpack.  UMBILICAL-CORD BLOOD , 1950 .

[42]  T. Takayama,et al.  Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion , 2005 .

[43]  A. Caplan,et al.  Cell surface antigens on human marrow-derived mesenchymal cells are detected by monoclonal antibodies. , 1992, Bone.