Heparin-binding growth factor 1 induces the formation of organoid neovascular structures in vivo.
One of the promises of modern molecular biology has been the opportunity to use genetically modified human cells in a patient to permanently restore inborn errors of metabolism. Although it has been possible to introduce genes into mammalian cells and to control their expression, it has proven difficult to introduce mammalian cells as carriers of the modified genetic information into hosts. The successful implantation of selective cells cannot be achieved without adequate vascular support, an essential step toward integration and reconstitution of a new biological function. Although a partial solution to this problem has been found by inducing specific site-directed neovessel formation using heparin-binding growth factor 1 (HBGF-1) adsorbed to a collagen matrix, these implants function for only a short period (weeks). We now report the formation of organoid neovascular structures using polytetrafluoroethylene fibers coated with collagen and HBGF-1 implanted in the peritoneal cavity of the rat. The organoid structures contained readily visible vascular lumina and nonvascular structures that resemble nerve tissue. It was also possible to demonstrate that the vascular system on the implant is continuous with the vascular tree of the host. This feature was used to demonstrate that the organoid structures are capable of sustaining the biological function of implanted normal rat hepatocytes over long periods of time (months) in the homozygous Gunn rat, thereby facilitating future applications involving the delivery of new genetic information.
Thompson
J A
JA
Genetic Therapy, Inc., Gaithersburg, MD 20878.
Haudenschild
C C
CC
Anderson
K D
KD
DiPietro
J M
JM
Anderson
W F
WF
Maciag
T
T
D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen; D016220:Fibroblast Growth Factor 1; D006133:Growth Substances / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects; D016031:Liver Transplantation; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D009389:Neovascularization, Pathologic; D051381:Rats; D011911:Rats, Gunn; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains
D006133:Growth Substances; D008934:Mitogens; D016220:Fibroblast Growth Factor 1; D006493:Heparin; D003094:Collagen