Transient inhibition of liver regeneration in mice by transforming growth factor-beta 1 encapsulated in liposomes.
We determined whether transforming growth factor-beta 1 (TGF-beta 1) encapsulated in phosphatidylcholine and phosphatidylserine liposomes could inhibit the proliferative response of mouse liver subsequent to partial hepatectomy. C57BL/6 mice were hepatectomized (60%) or underwent laparotomy (control). Peak mitotic activity occurred 48 hr after hepatectomy, as did incorporation of [125I]IdUrd into dividing cells of the liver. The number of Kupffer cells in the regenerating liver was constant relative to liver size, and the uptake of circulating liposomes correlated with liver size and the number of Kupffer cells. Liposomes containing saline (control) or TGF-beta 1 were injected i.v. into hepatectomized mice 24 and 36 hr after the operation. Liposome-TGF-beta 1, but not control liposomes, significantly inhibited the uptake of [125I]IdUrd by liver cells when measured 48 hr after hepatectomy. However, by 72 hr after hepatectomy, the uptake of [125I]IdUrd in livers of mice treated with liposome-TGF-beta 1 was similar to or exceeded that found for hepatectomized mice injected with control liposomes. We conclude that liposomes containing TGF-beta 1 can postpone the proliferative response of regenerating mouse liver cells and are therefore suitable carriers for the in vivo use of TGF-beta 1.
Schackert
H K
HK
Department of Cell Biology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Fan
D
D
Fidler
I J
IJ
D000818:Animals; D004337:Drug Carriers; D006498:Hepatectomy; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects; D008081:Liposomes; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008115:Liver Regeneration / Q000187:drug effects*; D008233:Lymphotoxin-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008940:Mitotic Index; D010713:Phosphatidylcholines; D010718:Phosphatidylserines
D004337:Drug Carriers; D008081:Liposomes; D008233:Lymphotoxin-alpha; D010713:Phosphatidylcholines; D010718:Phosphatidylserines