In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells.
In addition to long-term self-renewal capability, human mesenchymal stem cells (MSCs) possess versatile differentiation potential ranging from mesenchyme-related multipotency to neuroectodermal and endodermal competency. Of particular concern is hepatogenic potential that can be used for liver-directed stem cell therapy and transplantation. In this study, we have investigated whether human umbilical cord blood (UCB)-derived MSCs are also able to differentiate into hepatocyte-like cells. MSCs isolated from UCB were cultured under the pro-hepatogenic condition similar to that for bone marrow (BM)-derived MSCs. Expression of a variety of hepatic lineage markers was analyzed by flow cytometry, RT-PCR, Western blot, and immunofluorescence. The functionality of differentiated cells was assessed by their ability to incorporate DiI-acetylated low-density lipoprotein (DiI-Ac-LDL). As the cells were morphologically transformed into hepatocyte-like cells, they expressed Thy-1, c-Kit, and Flt-3 at the cell surface, as well as albumin, alpha-fetoprotein, and cytokeratin-18 and 19 in the interior. Moreover, about a half of the cells were found to acquire the capability to transport DiI-Ac-LDL. Based on these observations, and taking into account immense advantages of UCB over other stem cell sources, we conclude that UCB-derived MSCs retain hepatogenic potential suitable for cell therapy and transplantation against intractable liver diseases.
Hong
Seung Hyun
SH
Research Institute of Biotechnology, Histostem Co., Seoul, Republic of Korea.
Gang
Eun Ji
EJ
Jeong
Ju Ah
JA
Ahn
Chiyoung
C
Hwang
Soo Han
SH
Yang
Il Ho
IH
Park
Hwon Kyum
HK
Han
Hoon
H
Kim
Hoeon
H
D000107:Acetylation; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D008077:Lipoproteins, LDL