Hepatocyte transplantation program: Lessons learned and future strategies

This review aims to share the lessons we learned over time during the setting of the hepatocyte transplantation(HT) program at the Hepatic Cell Therapy Unit at Hospital La Fe in Valencia. New sources of liver tissue for hepatocyte isolation have been explored. The hepatocyte isolation and cryopreservation procedures have been optimized and quality criteria for assessment of functionality of hepatocyte preparations and suitability for HT have been established. The results indicate that:(1) Only highly viable and functional hepatocytes allow to recover those functions lacking in the native liver;(2) Organs with steatosis(≥ 40%) and from elderly donors are declined since low hepatocyte yields, viability and cell survival after cryopreservation, are obtained;(3) Neonatal hepatocytes are cryopreserved without significant loss of viability or function representing high-quality cells to improve human HT;(4) Cryopreservation has the advantage of providing hepatocytes constantly available and of allowing the quality evaluation and suitability for transplantation; and(5) Our results from 5 adults with acute liver failure and 4 from children with inborn metabolic diseases, indicate that HT could be a veryuseful and safe cell therapy, as long as viable and metabolically functional human hepatocytes are used.     

WFH: back to the future

Summary.  This paper outlines the history of the World Federation of Hemophilia (WFH) and its work. The WFH produces a number of publications each year, and conducts regular surveys and data collection. Two of its most important roles are in the provisions of programmes to developing countries, and in promoting the views of the haemophilia community on issues that impact on the lives of people with haemophilia. Further initiatives are planned in the future to increase the length and quality of life for those living with haemophilia.     

Benestent II: back to the future

It has been shown repeatedly in animal and clinical studies that heparin coating reduces thrombotic complications of several surfaces in contact with flowing blood. The demonstration that implantation of heparin-coated coronary stents is also effective in prevention of subacute thrombotic occlusion in a pig model offers the perspective of a clinical role of this treatment too. In order to put this to the test, the Benestent II pilot trial has been designed. This study will be conducted in a stepwise fashion in order to explore the feasibility of delaying deep anticoagulation as much as possible. Therefore, the primary goal is to minimize or exclude the need for heparin treatment following stent implantation. In addition, the effects on the need for revascularization procedures during follow-up will be recorded as well as the late morphological consequences as measured with quantitative coronary angiography.     

Rotational ablation: back to the future

In the late 1980s, many alternative methods to coronary angioplasty were sought, among which rotational ablation was one of the most popular. With the huge development of coronary stents, this technique, however, was progressively left aside. More recently, though, rotational ablation has reappeared as a unique technique for the most calcified lesions and is used in a small but not negligible percentage of patients with success rates over 95% in recent series.     

Hepatocyte transplantation

The purpose of this report is to summarize data collected over the past several years in the field of hepatocyte transplantation. Herein, a novel method of intraperitoneal transplantation of hepatocytes attached to collagen-coated microcarriers (or a totally biodegradable collagen sponge) is described, resulting in correction of specific genetic liver defects in rats and improved survival in rats undergoing 90% partial hepatectomy. Transplanted cells/matrix form well-vascularized aggregates in the peritoneal cavity; transplanted hepatocytes can be identified by light microscopy using immunohistochemical methods. Prolongation of transplanted hepatocyte survival and function was demonstrated by pretreatment of cells with ultraviolet irradiation. The ability of transplanted cells to proliferate was examined using both biochemical and morphologic criteria. Finally, a method of harvesting, cryopreserving, andin vivo functional testing of human hepatocytes is described.Presented at the Proceedings of the International Meeting on Normal and Neoplastic Growth in Hepatology, Bari, Italy, June 1989.Supported by National Institutes of Health (NIDDK) grant DK38763 and a Veterans Administration Merit Review Award.     

Hepatocyte transplantation

Repopulation of the liver with transplanted cells holds significant promise for developing novel therapies. The liver is a most suitable target for treating a variety of genetic, metabolic and acquired diseases. Liver disease, such as chronic viral hepatitis, constitutes an enormous burden worldwide. Advancing liver cell therapy requires insights into mechanisms of cell engraftment and proliferation, as well as unique requirements of specific diseases for correction by cell transplantation. This review highlights recent developments in the area of hepatocyte transplantation. Aspects concerning modulation of cell engraftment, regulation of gene expression and proliferation of transplanted cells are discussed. Other issues concern the current status of clinical applications of hepatocyte transplantation, as well as novel sources of cells that could benefit cell therapy in the future. The general conclusion is that cell therapy has become more practical in recent years and insights into how the normal liver and the diseased liver can be repopulated will offer effective ways to treat many disorders in the near future.     

Regulatory T cells: back to the future

Regulatory T cells seem to represent the resurrection of the old suppressor T cells. Although of a different phenotype, regulatory T cells are able to suppress many T cell mediated immune responses. While most basic knowledge about these cells is derived from animal studies, the recent identification of these cells in humans has further attributed to their characterisation by in vitro analysis. Results obtained have led to broad speculations about therapeutic potential by interference with these regulatory T cells. This review is an introduction to the world of regulatory T cells and contains an historical overview with respect to the identification and characterisation of these T cells. A distinction is made between naturally occurring regulatory T cells (nT(reg)), which require cell-cell contact for suppression, and inducible regulatory T cells (iT(reg)), which predominantly mediate suppression via cytokine dependent pathways. Although only limited studies on regulatory T cells in human disease are available today, the possible clinical applications are discussed in light of the other side of the coin, i.e. the danger of interfering with homeostatic mechanisms in the immune system.     

Hepatocyte transplantation: State of the art

Advances in biotechnology have allowed hepatocyte transplantation as a relevant proposition to treat liver disease. This procedure may change the crescent mortality in liver transplantation waiting lists due global organ shortage. Recent clinical trials have described promising results of hepatocyte transplantation for acute, acute-on-chronic and metabolic liver disease. In this report, we discuss progresses regarding hepatocyte culture, cryopreservation systems, hepatocyte immortalization, suitable recipient site for hepatocyte engraftment, cell differentiation and fusion into hepatocytes, current clinical trials, and summarize the bioartificial liver systems. These progressions motivate expectation concerning hepatocyte transplantation as a consistent therapy for liver disease.     

From Roma88 to Roma99: back to the future

Some objectives of the Rome International Congress of Gastroenterology and Digestive Endoscopy (1988) and their development during the past eleven years are described in the perspective of Roma99, the Seventh United European Gastroenterology Week.     

Hopeful thinking in older adults: back to the future

In a sample of 100 community-dwelling older adults (mean age of 76), higher hope related to greater life satisfaction and better perceived physical health, but hope did not relate to number of illnesses or functional disability. The high-relative to low-hope participants were more confident of reaching their goals, and felt that they were further along in their goal pursuits. The implications of these findings are discussed.