Irradiation as preparative regimen for hepatocyte transplantation causes prolonged cell cycle block

Abstract

IR leads to a major arrest in the G(1)/S phase and to a lesser extent in the G(2)/M transition of the cell cycle, resulting in reduced regenerative response following PH. The persistent block of at least four weeks may promote preferential proliferation of transplanted hepatocytes in this milieu.

Fractionated External Beam Radiotherapy as a Suitable Preparative Regimen for Hepatocyte Transplantation After Partial Hepatectomy

“…Recent studies of the workgroup achieved substantial liver repopulation using regional external beam irradiation (IR) to reduce the mitotic capacity of host hepatocytes followed by partial hepatectomy (PH). These techniques combined acted as a strong selective proliferation stimulus before donor cell transplantation (10)(11)(12). Our work is in line with the results of others demonstrating that the damage of hepatic IR may be ameliorated by subsequent hepatocyte transplantation (13,14).…”

“…External beam IR was performed as described previously (10,11). In brief, a planning computed tomography (CT) scan (Somatom Balance, Siemens, Erlangen, Germany) was performed on each rat in prone position on a 1-cm Perspex plate to delineate the livers of the animals.…”

Clinical Hepatocyte Transplantation: Practical Limits and Possible Solutions

“…Another strategy adopted in preclinical studies is the growth inhibition of the native cells by radiation or drugs, such as the plant alkaloids, retrorsine, or monocrotaline [82,83,84,85]. Although many of these strategies are not clinically acceptable, they provide proof of concept that, once integrated, donor hepatocytes must have a selective growth advantage over resident hepatocytes to highly repopulate a host liver [82,86,87,88,89]. …”

Allogeneic Liver Transplantation and Subsequent Syngeneic Hepatocyte Transplantation in a Rat Model: Proof of Concept for in vivo Tissue Engineering

“…This may be achieved via drug-induced growth arrest of host liver cells [Laconi et al, 1999;Brilliant et al, 2009;Yu et al, 2010] with genetically modified recipients [Rhim et al, 1994;Overturf et al, 1996;Mignon et al, 1998;Wu and Gupta, 2009] or liver-directed radiation as a preconditioning regimen [Koenig et al, 2008;Yamanouchi et al, 2009]. These methods do not seem suitable for human liver cell transplantation.…”