Permanent engraftment and function of hepatocytes delivered to the liver: Implications for gene therapy and Liver Repopulation
✍ Scribed by Sanjeev Gupta; Emma Aragona; Ravikumar P. Vemuru; Kuldeep K. Bhargava; Robert D. Burk; Jayanta Roy Chowdhury
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- English
- Weight
- 715 KB
- Volume
- 14
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
To examine the distribution of intrasplenically transplanted hepatocytes, we used HBsAg-producing 6 7 HBV transgenic hepatocytes or cells labeled with '"In. Most hepatocytes translocated to the liver (55% f 7%; mean k S.D.); the spleen retained a smaller fraction (15% * 3%); and some transplanted cells localized in lungs (3%) or pancreas (1%). Transplanted hepatocytes were rapidly assimilated into the liver lobule. Morphometrical quantitation indicated that the numbers of transplanted hepatocytes in the liver at 48 hr and at 9 mo after transplantation were similar. Serum HBsAg was detected in recipients of the 6 7 HBV hepatocytes during the 1-yr experiment. These results indicate that a large number of hepatocytes can be reproducibly delivered to the liver by transplantation into the spleen. Transplanted hepatocytes engraft rapidly, assimilate into host liver, maintain normal function and survive permanently. Systems for safe delivery and localization of hepatocytes in the liver represent a critical step toward successfully accomplishing hepatocyte-directed gene therapy and repopulation of the acutely devastated liver. (HEPA-TQLOGY 1991;14:144-149.)
Hepatocyte-directed gene therapy and repopulation of the devastated liver would be valuable new additions to our therapeutic armamentarium. Theoretically, liver should be the ideal recipient site for hepatocytes. However, distinguishing between host and transplanted liver cells has been problematic. Therefore, to determine whether transplanted hepatocytes could survive and function, investigators have used various heterologous sites (1-6). The therapeutic potential of hepatocyte transplantation was explored in models of metabolic