- Namita Roy-Chowdhury, PhD
Namita Roy-Chowdhury, PhD
- Professor of Medicine and Genetics
- Albert Einstein College of Medicine
- Jayanta Roy-Chowdhury, MD, MRCP
Jayanta Roy-Chowdhury, MD, MRCP
- Professor of Medicine and Genetics
- Albert Einstein College of Medicine
- Section Editor
- Robert S Brown, Jr, MD, MPH
Robert S Brown, Jr, MD, MPH
- Section Editor — Liver Transplantation
- Vice Chair, Transitions of Care, Department of Medicine
- Interim Chief, Division of Gastroenterology and Hepatology
- Weill Cornell Medical College
- Professor of Clinical Medicine, Columbia University College of Physicians & Surgeons
Advances in the understanding of hepatocyte engraftment and the remarkable proliferative potential of hepatocytes have brought liver cell transplantation to the doorstep of application in the treatment of inherited and acquired human diseases. Extensive animal experiments have shown that hepatocytes transplanted in the liver or at ectopic sites survive, function, and participate in the regenerative process. Because the host liver architecture remains intact following the integration of the engrafted hepatocytes in the liver cords, hepatocyte transplantation is metabolically less stressful than transplantation of the whole organ, and the consequences of graft loss are much less severe.
Hepatocyte transplantation has many potential applications. Therapeutic genes can be transferred into cultured hepatocytes, and the phenotypically modified cells can then be transplanted for ex vivo gene therapy. Such gene transfer could be used to replace a missing gene product or to prevent immune rejection. Gene therapy of the host is also being explored for prevention of rejection of allografted or xenografted hepatocytes. Hepatocyte transplantation does not interfere with subsequent liver transplantation or gene therapy. Although the clinical efficacy of hepatocyte transplantation has been demonstrated, the shortage of good quality donor livers for hepatocyte isolation and the lack of dependable methods of cryopreservation will limit widespread clinical application of this method until further research overcomes these problems.
SCOPE OF HEPATOCYTE TRANSPLANTATION
As mentioned above, hepatocyte transplantation has many potential clinical applications (table 1).
Treatment of inherited metabolic diseases — Missing gene products can be substituted by transplanting normal primary hepatocytes from allogeneic donors. This simple approach holds promise for diseases such as Crigler-Najjar syndrome type 1, urea cycle disorders, and coagulopathies, including hemophilias. In addition, gene therapy can aid in abolishing or decreasing immune response against allografts or xenografts and promote repopulation of transplanted cells. (See "Crigler-Najjar syndrome" and "Inborn errors of metabolism: Classification", section on 'Urea cycle disorders' and "Genetics of the hemophilias".)
Hepatocytes used for gene therapy can be derived from a separate donor (allogeneic transplantation) or the recipient, in which case the genetic defect needs to be corrected before transplantation (autologous transplantation). An advantage of autologous transplantation is that it does not require immunosuppression [1-3].
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- SCOPE OF HEPATOCYTE TRANSPLANTATION
- Treatment of inherited metabolic diseases
- Management of acute liver failure
- Management of chronic liver failure
- SOURCES OF HEPATOCYTES
- SITES OF HEPATOCYTE TRANSPLANTATION
- PRECLINICAL EVALUATION IN EXPERIMENTAL ANIMAL MODELS
- Animal models of disorders due to single gene defects
- Animal models of acute and chronic liver failure
- Massive repopulation of the liver
- Ex vivo gene therapy
- CLINICAL EXPERIENCE
- Hepatocyte transplantation for metabolic disorders
- Hepatocyte transplantation for liver failure
- Hepatocyte transplantation for ex vivo gene therapy
- EXISTING HURDLES AND CURRENT RESEARCH