Factors influencing hepatocyte trafficking during allogeneic hepatocyte transplantation: Improved liver sequestration with isolated perfusion Journal Article

  

Authors:	Picardo, A.; Fong, Y.; Karpoff, H. M.; Yeh, S.; Blumgart, L. H.; Brennan, M. F.
Article Title:	Factors influencing hepatocyte trafficking during allogeneic hepatocyte transplantation: Improved liver sequestration with isolated perfusion
Abstract:	Transplantation of normal or ex vivo modified hepatocytes holds promise in therapy of a variety of diseases. In order to investigate hepatocyte trafficking, and specifically to determine whether the route, method of delivery, or other host factors may affect hepatocyte sequestration in the liver, 51chromium- and 111indium-labeled hepatocytes were transplanted into allogeneic hosts. Systemic injection of hepatocytes into the femoral vein resulted in sequestration mainly in the lungs (30 ± 4%) whereas sequestration in the liver amounted to only 5 ± 1%. Portal injection resulted in a dramatic increase in the liver sequestration (52 ± 4%) and a reduction in the lung (2 ± 1%, P < 0.05 vs systemic injection). Nevertheless, nearly half of portally injected hepatocytes came to rest in other organ sites. Partial hepatectomy prior to transplantation did not change the total hepatocyte sequestration in the liver or the organ specific activity. A remote site of inflammation, in the form of a turpentine abscess, also did not alter the pattern of hepatocyte trafficking. Isolated perfusion of the liver with labeled hepatocyte, however, significantly increased the sequestration of hepatocytes at this organ (control, 52 ± 4%; isolated perfusion, 71 ± 9%; P < 0.05). In the delivery of potentially toxic gene products for therapy, isolated perfusion of the target organ appears to provide the greatest likelihood of restricting expression of potentially toxic gene products to the target organ.
Keywords:	controlled study; nonhuman; animal cell; animal tissue; gene targeting; animal experiment; gene product; rat; gene therapy; kupffer cell; liver cell; allotransplantation; partial hepatectomy; cell transplantation; cell labeling; liver perfusion; lung sequestration; chromium; indium; male; priority journal; article; isolated liver
Journal Title:	Journal of Surgical Research
Volume:	63
Issue:	2
ISSN:	0022-4804
Publisher:	Academic Press Inc., Elsevier Science
Date Published:	1996-07-01
Start Page:	452
End Page:	456
Language:	English
DOI:	10.1006/jsre.1996.0291
PUBMED:	8661241
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0030199630&doi=10.1006%2fjsre.1996.0291&partnerID=40&md5=a04dbe2998264a15cbdf151e3ea027ef
Notes:	Article -- Export Date: 22 November 2017 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/119159