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Open Access Normal Hepatocyte Transplantation Delays the Emergence of Chemically Induced Preneoplastic Nodules in Rat Liver

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Abstract:

Cancer often arises in a background of chronic tissue damage. It is also increasingly appreciated that such an injured tissue microenvironment might foster the selective emergence of altered cells, leading to neoplasia. Accordingly, reversal of chronic tissue damage could represent a potential strategy to counteract neoplastic disease. In these studies, we aim to investigate whether transplantation of normal cells in the context of an injured, neoplastic-prone microenvironment might impact on the evolution of the carcinogenic process. A rat model of chemically induced hepatocarcinogenesis was used. Animals were given a single dose of diethylnitrosamine (DENA), followed by two injections of retrorsine (RS), a pyrrolizidine alkaloid that imposes a persistent block on hepatocyte cell cycle. At the end of this protocol, rats were either given no further treatment or injected, via the portal circulation, with 4 million normal hepatocytes isolated from a syngenic donor. After 3 months, rats given DENA+RS alone displayed numerous discrete nodular lesions (up to 30 per liver), ranging 1 to 3 mm in size. On the other hand, in animals receiving DENA+RS and transplantation, donor hepatocytes were able to repopulate over 50% of the host liver, as expected. Most importantly, both the number and the size of hepatocyte nodules were greatly reduced in these animals (percent nodular area was 1.8 ± 0.3, down from a control value of 8.5 ± 2.8). The above data indicate that strategies aimed at reestablishing a normal tissue microenvironment might be relevant to the management of neoplastic disease.

Keywords: Cell competition; Cell transplantation; Liver carcinogenesis; Liver repopulation; Tumor microenvironment

Document Type: Research Article

DOI: https://doi.org/10.3727/096368911X600975

Affiliations: Department of Biomedical Sciences, Unit of Experimental Medicine, University of Cagliari, Cagliari, Italy

Publication date: 2012-04-01

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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