RETRACTED: Heparin-binding growth factor 1 induces the formation of organoid neovascular structures in vivo.

Abstract

One of the promises of modem 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 heparinbinding 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.Angiogenesis involves the orderly migration and proliferation of blood vessels and occurs during development (1,2). Although angiogenesis is an infrequent event in the adult, mainly associated with wound and fracture repair, exceptions are found in the female reproductive system, where this process occurs in the follicle during development, in the corpus luteum during ovulation, and in the placenta during pregnancy (1, 2). These physiologic, specific periods of angiogenesis are relatively brief and highly regulated in contrast to the pathologic angiogenic events associated with tumor growth, diabetic retinopathy, and other disorders. Because the endothelial cell is considered to be the primary cell involved in all forms of angiogenesis, efforts have concentrated on the identity of polypeptide factors that control endothelial cell proliferation (1,2). Indeed, the heparinbinding growth factor (HBGF) family of polypeptides has gained general acceptance as initiators of angiogenesis especially during development (1)(2)(3)(4)(5)(6). This gene family includes the prototypes HBGF-1 (acidic fibroblast growth factor), HBGF-2 (basic fibroblast growth factor), and three additional HBGF-like structures, hst/KS, int-2, and fibroblast growth factor 5 (2, 5). HBGF-1 and HBGF-2 are potent inducers of endothelial cell migration and/or proliferation in vitro (1, 2, 7) and are known to modulate the expression of endothelial cell-derived proteases (8-13). Further, the HBGF prototypes are tightl...

In vivo electroporation and stable transformation of skin cells of newborn mice by plasmid DNA

“…Normal rat primary hepatocyte culture could be seeded into the network of the vascularized fibers and implanted near the liver of the rat lacking the enzyme conjugating bilirnbin. The decreased level of bilirubin in the blood of recipient rats could be maintained at least 181 days in the presence of viable hepatocytes and neovascular structure [8].…”

Heat shock induces the release of fibroblast growth factor 1 from NIH 3T3 cells.

“…While the expression and translocation of HSP70 between organelles is cell cycle-specific (25) and has been reported to be associated with physiologic vascular stress (26)(27)(28), the function of these stress proteins in diseases associated with fever, inflammation, cellular hypertrophy, or programmed cell death (29-32) remains unknown. Because (i) the expression of FGF-1 is exaggerated in inflamed cartilage in vivo (33), (ii) FGF-1 is a potent regulator of cellular hypertrophy (34), and (iii) programmed cell death has been proposed as a mechanism for the release ofcytosolic FGF-1 (1-3, 8), we examined the role of heat-induced stress as a potential mechanism for the secretion ofFGF-1 in vitro and report here that the release of cytosolic FGF-1 is regulated by temperature in vitro.…”

Site‐specific delivery of acidic fibroblast growth factor stimulates angiogenic and osteogenic responses in vivo

“…Numerous mesoderm‐derived cells, including those derived from the musculoskeletal system, both express and respond to FGF‐1 62–66 . In vivo , FGF‐1 is a potent inducer of both angiogenesis,20–22 an established requisite for bone repair,19 and osteogenesis during normal bone development and fracture healing 42. One of the immediate responses following fracture trauma includes the increased appearance of cytokines and growth factors, including FGF‐1,19 at the site of injury.…”

“…Immediately following fracture trauma, increased expression of FGF‐1 and FGF‐2 are observed at the injury site 19 . In vivo , FGF‐1 is a potent inducer of both angiogenesis,20–22 an established requisite for bone repair, and osteogenesis during normal bone development and repair 19. Interestingly, several skeletal disorders in humans, such as achondroplasia and both Jackson–Weiss and Cruzon syndrome, have been related to mutations within specific FGF receptors 23–25…”