Human Cord Blood Stem Cells Generate Human Cytokeratin 18-Negative Hepatocyte-Like Cells in Injured Mouse Liver

• Published in: The American journal of pathology Vol. 167; no. 2; pp. 555 - 564
• Main Authors: Sharma, Amar Deep, Cantz, Tobias, Richter, Rudolf, Eckert, Klaus, Henschler, Reinhard, Wilkens, Ludwig, Jochheim-Richter, Andrea, Arseniev, Lubomir, Ott, Michael
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.08.2005; ASIP; American Society for Investigative Pathology
• Subjects: Animals; Biological and medical sciences; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Bone Marrow Transplantation; Carbon Tetrachloride - toxicity; Cell Differentiation; Cord Blood Stem Cell Transplantation; Female; Fetal Blood - cytology; Fetal Blood - metabolism; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - physiology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Hepatocyte Growth Factor - pharmacology; Hepatocytes - cytology; Hepatocytes - metabolism; Humans; Investigative techniques, diagnostic techniques (general aspects); Keratins - metabolism; Liver - injuries; Liver - metabolism; Liver Regeneration; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, SCID; Mice, Transgenic; Original Research Paper; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Transplantation, Heterologous; Human; Cytokeratin; Digestive system; Stem cell; Liver; Rodentia; Blood; Vertebrata; Anatomic pathology; Blood cell; Mammalia; Hepatocyte; Mouse; Animal; Umbilical cord
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)62997-5

Differentiation of adult bone marrow (BM) cells into nonhematopoietic cells is a rare phenomenon. Several reports, however, suggest that human umbilical cord blood (hUCB)-derived cells give rise to hepatocytes after transplantation into nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice. Therefore, we analyzed the hepatic differentiation potential of hUCB cells and compared the frequency of newly formed hepatocyte-like cells in the livers of recipient NOD-SCID mice after transplantation of hUCB versus murine BM cells. Mononuclear cell preparations of hUCB cells or murine BM from enhanced green fluorescent protein transgenic or wild-type mice were transplanted into sublethally irradiated NOD-SCID mice. Liver regeneration was induced by carbon tetrachloride injury with and without sub-sequent hepatocyte growth factor treatment. By immunohistochemistry and reverse transcriptase-polymerase chain reaction, we detected clusters of hepatocyte-like cells in the livers of hUCB-transplanted mice. These cells expressed human albumin and Hep Par 1 but mouse CK18, suggesting the formation of chimeric hepatocyte-like cells. Native fluorescence microscopy and double immunofluorescence failed to detect single hepatocytes derived from transplanted enhanced green fluorescent protein-transgenic mouse BM. Fluorescent in situ hybridization rarely revealed donor-derived hepatocyte-like cells after cross-gender mouse BM transplantation. Thus, hUCB cells have differentiation capabilities different from murine BM cells after transplantation into NOD-SCID mice, demonstrating the importance of further testing before hUCB cells can be used therapeutically.