Blood-brain barrier formation of grafted human umbilical vein endothelial cells in athymic mouse brain

Human umbilical vein endothelial cells (HUVECs) were transplanted in athymic mouse brain and neovascularization of grafted endothelial cells was studied. HUVECs were transfected by a reporter gene pEGFPE-N1 in vitro and grafted stereotactically in unilateral striatum of adult nude mice. Histological studies in 4 weeks revealed that grafted HUVECs newly formed microvessels in brain, which were migrated and fused with host vessels. Intravenous injection of Evans blue before sacrificing animals resulted in no extravasation of dye, indicating that a blood-brain barrier (BBB) was formed by the grafted HUVECs. Immunohistochemistry demonstrated that host astrocytes extended glial feet on the grafted endothelial cells and a part of the newly formed vessels was positive with glucose transporter-1. These results indicate that endothelial cells from an ectopic origin have the potential to form a BBB after grafting in the central nervous system.

[1]  M. Grady,et al.  Blood-brain barrier permeability is not altered by allograft or xenograft fetal neural cell suspension grafts , 1991, Experimental Neurology.

[2]  J C Stanley,et al.  Adhesion and incorporation of lacZ-transduced endothelial cells into the intact capillary wall in the rat. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[3]  R. Broadwell,et al.  Contributions of Donor and Host Blood Vessels in CNS Allografts , 1996, Experimental Neurology.

[4]  E. Nabel,et al.  Recombinant gene expression in vivo within endothelial cells of the arterial wall. , 1989, Science.

[5]  S. Kohsaka,et al.  Mosaic reconstruction of blood vessels in mouse neocortical tissue transplanted into the third ventricle of rat brain , 1989, Brain Research.

[6]  J. Zimmer,et al.  Neocortical transplants grafted into the newborn rat brain demonstrate a blood-brain barrier to macromolecules , 1989, Neuroscience Letters.

[7]  R. Forough,et al.  Angiogenesis-directed implantation of genetically modified endothelial cells in mice. , 1995, Cancer research.

[8]  G. Bowlin,et al.  Electrostatic endothelial cell seeding technique for small-diameter (<6 mm) vascular prostheses: feasibility testing. , 1997, Cell transplantation.

[9]  R. Liblau,et al.  Gene transfer to the central nervous system by transplantation of cerebral endothelial cells , 1997, Gene Therapy.

[10]  R. Shivers,et al.  Astrocyte-mediated induction of tight junctions in brain capillary endothelium: an efficient in vitro model. , 1987, Brain research.

[11]  R. Janzer,et al.  Astrocytes induce blood–brain barrier properties in endothelial cells , 1987, Nature.

[12]  G. Goldstein,et al.  Endothelial cell implantation and survival within experimental gliomas. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[13]  L. Garcia-Segura,et al.  Astroglial Induction of in vivo Angiogenesis , 1994, Journal of neural transplantation & plasticity.

[14]  Hiroshi Yamamoto,et al.  Induction of various blood‐brain barrier properties in non‐neural endothelial cells by close apposition to co‐cultured astrocytes , 1997, Glia.

[15]  J. Rosenstein,et al.  Immunocytochemical expression of the blood—brain barrier glucose transporter (GLUT‐1) in neural transplants and brain wounds , 1994, The Journal of comparative neurology.

[16]  R. Broadwell,et al.  Allografts of CNS tissue possess a blood-brain barrier II. Angiogenesis in solid tissue and cell suspension grafts , 1991, Experimental Neurology.

[17]  A. Granholm,et al.  DEVELOPMENT OF AN INTACT BLOOD-BRAIN BARRIER IN BRAIN TISSUE TRANSPLANTS IS DEPENDENT ON THE SITE OF TRANSPLANTATION. , 1996, Cell transplantation.