Survival, organization, and function of microcarrier-attached hepatocytes transplanted in rats.

Demetriou, Achilles A.; Levenson, Stanley M.; Novikoff, Phyllis M.; Novikoff, Alex B.; Chowdhury, Namita Roy; Whiting, James F.; Reisner, Andrew; Chowdhury, Jayanta Roy

doi:10.1073/pnas.83.19.7475

Cited by 131 publications

(17 citation statements)

References 18 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A gradual decrease to >60% was observed for the duration of the experiment (Fig. 3B) (40,41) has overcome some of these limitations since the hepatocytes are on the surface of beads allowing attached cells to obtain adequate nutrition to remain metabolically active. The main advantage of the PTFE fiber implant model, in contrast to injecting a suspension of beads, is that the solid support containing attached cells can be both site-specifically implanted and retrieved as a complete entity, thereby allowing convenient posttransplant biochemical analysis.…”

Section: Methodsmentioning

confidence: 99%

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

Thompson¹,

Haudenschild²,

Anderson³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.Retracted 1992-8-15 Has erratum 1992-8-15

122

View full text Add to dashboard Buy / Rent full text

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...

show abstract

Section: Methodsmentioning

confidence: 99%

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

Thompson¹,

Haudenschild²,

Anderson³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.Retracted 1992-8-15 Has erratum 1992-8-15

122

View full text Add to dashboard Buy / Rent full text

show abstract

“…The simplest method for cell therapies is by transplantation of primary hepatocytes isolated from the donor. Experimental studies on animals have shown that transplanted primary hepatocytes into the spleen or portal vein of host animals repopulated in the liver, suggesting that the primary hepatocyte transplantation may be successful as an alternative to organ transplantation for patients with liver failure (Sutherland et al, 1977;Makowka L et al, 1980;Demetrious et al, 1986;Arkadopoulos et al, 1998;Ribeiro et al, 1992;Ito et al, 2007;Nagata et al, 2003;Kobayashi et al, 2000). However, success in clinical use is limited Platt, 1998) and donor human livers to isolate the hepatocytes for hepatocyte transplantations are also limited, since these organs are needed to use in organ transplantation.…”

Section: Introductionmentioning

confidence: 99%

A Strategy Using Pluripotent Stem Cell-Derived Hepatocytes for Stem Cell-Based Therapies

Tomotsune¹,

Sato²,

Yoshie³

et al. 2011

Advances in Regenerative Medicine

View full text Add to dashboard Buy / Rent full text

“…The advantage of using the Gunn rat model is that the function of the engrafted normal hepatocytes can be evaluated by the determination of serum bilirubin levels, excretion of bilirubin glucuronides in bile and UGT1A1 activity in liver biopsy specimens. 19 …”

Section: Irradiation and Fasl Expression For Hepatic Repopulation M Tmentioning

confidence: 99%

A novel strategy for in vivo expansion of transplanted hepatocytes using preparative hepatic irradiation and FasL-induced hepatocellular apoptosis

et al. 2003

View full text Add to dashboard Buy / Rent full text

A strategy for inducing preferential proliferation of the engrafted hepatocytes over host liver cells should markedly increase the benefit of hepatocyte transplantation for the treatment of liver diseases and ex vivo gene therapy. We hypothesized that preparative hepatic irradiation (HIR) to inhibit host hepatocellular regeneration in combination with the mitotic stimulus of host hepatocellular apoptosis should permit repopulation of the liver by transplanted cells. To test this hypothesis, congeneic normal rat hepatocytes were transplanted into UDP-glucuronosyltransferase (UGT1A1)-deficient jaundiced Gunn rats (a model of Crigler-Najjar syndrome type I), following HIR and adenovirus-mediated FasL gene transfer. Progressive repopulation of the liver by engrafted UGT1A1-proficient hepatocytes over 5 months was demonstrated by the appearance of UGT1A1 protein and enzyme activity in the liver, biliary bilirubin glucuronides secretion, and long-term normalization of serum bilirubin levels. This is the first demonstration of massive hepatic repopulation by transplanted cells by HIR and FasL-induced controlled apoptosis of host liver cells.

show abstract

Survival, organization, and function of microcarrier-attached hepatocytes transplanted in rats.

Cited by 131 publications

References 18 publications

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

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

A Strategy Using Pluripotent Stem Cell-Derived Hepatocytes for Stem Cell-Based Therapies

A novel strategy for in vivo expansion of transplanted hepatocytes using preparative hepatic irradiation and FasL-induced hepatocellular apoptosis

Contact Info

Product

Resources

About