title: Administration of bone marrow derived mesenchymal stem cells into the liver: potential to rescue pseudoxanthoma elasticum in a mouse model (Abcc6-/-).
abstract: Pseudoxanthoma elasticum (PXE) is a heritable ectopic mineralization disorder caused by loss-of-function mutations in the ABCC6 gene which is primarily expressed in the liver. There is currently no effective treatment for PXE. In this study, we characterized bone marrow derived mesenchymal stem cells (MSCs) and evaluated their ability to contribute to liver regeneration, with the aim to rescue PXE phenotype. The MSCs, isolated from GFP-transgenic mice by magnetic cell sorting, were shown to have high potential for hepatic differentiation, with expression of Abcc6, in culture. These cells were transplanted into the livers of 4-week-old immunodeficient Abcc6⁻/⁻ mice by intrasplenic injection one day after partial hepatectomy, when peak expression of the stromal cell derived factor-1 (SDF-1) in the liver was observed. Fluorescent bioimaging analyses indicated that transplanted MSCs homed into liver between day 1 and 7, and significant numbers of GFP-positive cells were confirmed in the liver by immunofluorescence. Moreover, enhanced engraftment efficiency was observed with MSCs with high expression levels of the chemokine receptor Cxcr4, a receptor for SDF-1. These data suggest that purified MSCs have the capability of differentiating into hepatic lineages relevant to PXE pathogenesis and may contribute to partial correction of the PXE phenotype.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, 233 S. 10th Street, Philadelphia, PA 19107, USA.
authors.forename: Qiujie
authors.initials: Q
authors.lastname: Jiang
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Takahagi
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D002465:Cell Movement; D002469:Cell Separation; D054377:Chemokine CXCL12 / Q000097:blood; D004195:Disease Models, Animal; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000601:surgery; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011561:Pseudoxanthoma Elasticum / Q000097:blood / Q000628:therapy*; D019718:Receptors, CXCR4 / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D000954:Antigens, Surface; D054377:Chemokine CXCL12; D015395:Histocompatibility Antigens Class I; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D019718:Receptors, CXCR4; C504743:Abcc6 protein, mouse