In utero transplantation of human bone marrow-derived multipotent mesenchymal stem cells in mice.
Mesenchymal stem cells (MSCs) are multipotent cells that can be isolated from human bone marrow and possess the potential to differentiate into progenies of embryonic mesoderm. However, current evidence is based predominantly on in vitro experiments. We used a murine model of in utero transplantation (IUT) to study the engraftment capabilities of human MSCs. MSCs were obtained from bone marrow by negative immunoselection and limiting dilution, and were characterized by flow cytometry and by in vitro differentiation into osteoblasts, chondrocytes, and adipocytes. MSCs were transplanted into fetal mice at a gestational age of 14 days. Engraftment of human MSCs was determined by flow cytometry, polymerase chain reaction, and fluorescence in situ hybridization (FISH). MSCs engrafted into tissues originating from all three germ layers and persisted for up to 4 months or more after delivery, as evidenced by the expression of the human-specific beta-2 microglobulin gene and by FISH for donor-derived cells. Donor-derived CD45+ cells were detectable in the peripheral blood of recipients, suggesting the participation of MSCs in hematopoiesis at the fetal stage. This model can further serve to evaluate possible applications of MSCs.
Department of Life Science, Fu-Jen University, 510 Zhongzheng Road, Hsinehuang City, Taipei 242, Taiwan, Republic of China. bio0004@mails.fju.edu.tw
Shiu-Huey
SH
Chou
Tom K
TK
Kuo
Ming
M
Liu
Oscar K
OK
Lee
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000166:cytology*; D015870:Gene Expression; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D014183:Transplantation, Heterologous; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D001613:beta 2-Microglobulin; D017493:Leukocyte Common Antigens