Functional Response of Hepatocytes Transplanted into Gunn Rats Stimulated with Thyroid Hormone

Abstract

In the attempt to translate laboratory studies into clinical practice, the small number of cells that can be transplanted is currently a problem to be solved. The aim of this work is to study the functional response of intrasplenically transplanted syngeneic rat adult and fetal hepatocytes to a proliferative stimulus, 3,5,3'-triiodothyronine. Total serum bilirubin significantly decreased from 7 to 90 days after fetal hepatocyte transplantation and from 24 hr to 30 days after adult hepatocyte transplantation. Concomitant with these changes, bile conjugated bilirubin increased from 7 to 90 days after fetal and from 24 hr to 30 days after adult hepatocyte transplantation. In both cases, administration of thyroid hormone enhances this effect. We conclude that although adult and fetal hepatocytes correct the hyperbilirubinemia, fetal cells function longer than adult hepatocytes. Thyroid hormone is a powerful stimulator of function of hepatocytes since it improves both adult and fetal response.

Therapeutic hepatocyte transplant for inherited metabolic disorders: functional considerations, recent outcomes and future prospects

“…Subsequently, deficiency of UGT1A1 was identified, representing a relevant phenocopy of CN I syndrome (McCandless 2011). A number of preclinical HTx studies have shown efficacy in this model, including application of immortalized hepatocytes, bone marrow-derived cells, as well as intrasplenic administration of both fetal and adult hepatocytes (Kawashita et al 2008); (Muraca et al 2007); (Cubero et al 2007); (Guha et al 2002). In these studies, engraftment advantage was achieved by irradiation, partial hepatectomy, or induction of ischemic/reperfusion injury to damage endogenous tissue.…”

Survival of Allogeneic Hepatocytes Transplanted into the Thymus

“…The development of strategies to give transplanted hepatocytes a selective advantage for proliferation over the cells of the recipient's liver is proving to be a difficult task [Cubero et al, 2007]. In many cases, the possibility of injecting cells in several locations would enhance the therapeutic potential of cell therapy, either because it helps to enlarge the tissue mass bringing it to the critical one or because it helps the generation of immunological tolerance.…”