In utero transplantation of human hematopoietic stem/progenitor cells partially repairs injured liver in mice.
The aim of this study is to establish a novel mouse model with high achievement and chimerism by in utero transplantation of human hematopoietic stem/progenitor cells and to explore the possibility that human adult hematopoietic stem/progenitor cells can differentiate into hepatocyte-like cells and partially repair the liver damage induced by carbon tetrachloride (CCl(4)). Mononuclear cells (MNCs) were isolated from fresh human umbilical cord blood (hUCB) and CD34(+) cells were enriched from the MNCs by magnetic cell isolation. These cells were injected respectively into the fetal mice at 11-13 days of gestation. At one month after birth, the specific markers of human cells, human alpha-satellite sequence (h17alpha), CD14, CD34, CD45, and GPA were detected by PCR and FACS. At three and six months after birth, the established human-mouse chimeras were administered with CCl(4) by intraperitoneal injection. The biochemical markers (ALT, AST, ALP, albumin) in serum were determined and human hepatocyte-specific proteins, such as human albumin, hepatocyte nuclear factor-4, hepatocyte-specific antigen, tryptophan 2,3-dioxygenase and alpha fetoprotein were analyzed by PCR, RT-PCR, real-time PCR and immunohistochemistry staining, respectively. More than 77% of recipients demonstrated human-mouse chimera. Significantly, hUCB hematopoietic stem/progenitor cells may differentiate into human hepatocyte-like cells with evidence of the expression of human hepatocyte-specific proteins as well as partially repair or protect liver damage induced by CCl(4). The mouse model described in this article provides a useful tool for the studies of regeneration of human hepatocyte-like cells from adult hematopoietic stem/ progenitor cells as well as facilitates the therapeutic potential for liver diseases or damage by in utero transplantation.
Qian
Hui
H
Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, P.R. China.
Wang
Juan
J
Wang
Shu
S
Gong
Zhijuan
Z
Chen
Meijue
M
Ren
Zhaorui
Z
Huang
Shuzhen
S
D000818:Animals; D000831:Animals, Newborn; D018952:Antigens, CD34 / Q000032:analysis / Q000097:blood; D001853:Bone Marrow / Q000737:chemistry; D002251:Carbon Tetrachloride / Q000633:toxicity; D002454:Cell Differentiation; D056486:Chemical and Drug Induced Liver Injury; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000166:cytology / Q000637:transplantation*; D005434:Flow Cytometry; D005865:Gestational Age; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000166:cytology / Q000637:transplantation; D008107:Liver Diseases / Q000196:embryology / Q000517:prevention & control*; D051379:Mice; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012709:Serum Albumin / Q000032:analysis / Q000235:genetics; D013154:Spleen / Q000737:chemistry; D014183:Transplantation, Heterologous
D018952:Antigens, CD34; D012709:Serum Albumin; D002251:Carbon Tetrachloride; D017493:Leukocyte Common Antigens