Survival, organization, and function of microcarrier-attached hepatocytes transplanted in rats

A. A. Demetriou, S. M. Levenson, P. M. Novikoff, N. R. Chowdhury, J. Whiting, A. Reisner, Jayanta Roy-Chowdhury

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

Hepatocytes harvested by collagenase perfusion of rat liver were attached to collagen-coated microcarriers and injected intraperitoneally into congeneic or allogeneic bilirubin-UDP-glucuronosyltransferase (EC 2.4.1.17)-deficient (Gunn) rats of allogeneic analbuminemic (NAR) rats. Five days later, the microcarriers were observed to have formed conglomerates chiefly on the anterior surface of the pancreas. Scanning electron microscopy showed hepatocytes attached to the granular collagen-coated surface of the microcarriers and newly formed connective tissue. Light microscopy revealed that the microcarriers formed a lattice with the collagen tissue; hepatocytes were seen within this lattice or on the surface of the microcarriers. Hepatocyte plasma membranes were nucleoside-diphosphatase (NDPase)-positive, Newly formed blood islands, blood vessels containing erythrocytes and leukocytes and NDPase-positive endothelium were observed in close proximity to the hepatocytes and fibroblasts. Transmission electron microscopic examination showed hepatocytes with microvilli and nucleoid-containing peroxisomes with catalase activity. Hepatocytes were present for up to 2 months in congeneic recipients, the longest period of observation after transplantation. After normal microcarrier-attached hepatocytes were transplanted into allogeneic Gunn rats, bilirubin glucuronides were present in bile for 6 days. When congeneic Gunn rat recipients were used, bilirubin glucuronides were present in bile throughout the study (28 days); this was accompanied by reduction of serum bilirubin concentrations to nearly normal levels. After injection of normal hepatocytes into allogeneic NAR rats, plasma albumin concentration progressively increased for 6 days and then declined. In NAR recipients which were immunosuppressed with cyclosporin A, peak plasma albumin levels were reached in 14 days and persisted nearly at that level throughout the study (28 days).

Original languageEnglish (US)
Pages (from-to)7475-7479
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume83
Issue number19
DOIs
StatePublished - 1986
Externally publishedYes

Fingerprint

Hepatocytes
Gunn Rats
Collagen
bilirubin glucuronoside glucuronosyltransferase
Bile
Serum Albumin
Peroxisomes
Collagenases
Microvilli
Bilirubin
Connective Tissue
Electron Scanning Microscopy
Catalase
Cyclosporine
Endothelium
Blood Vessels
Pancreas
Microscopy
Leukocytes
Perfusion

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Survival, organization, and function of microcarrier-attached hepatocytes transplanted in rats. / Demetriou, A. A.; Levenson, S. M.; Novikoff, P. M.; Chowdhury, N. R.; Whiting, J.; Reisner, A.; Roy-Chowdhury, Jayanta.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 83, No. 19, 1986, p. 7475-7479.

Research output: Contribution to journalArticle

Demetriou, A. A. ; Levenson, S. M. ; Novikoff, P. M. ; Chowdhury, N. R. ; Whiting, J. ; Reisner, A. ; Roy-Chowdhury, Jayanta. / Survival, organization, and function of microcarrier-attached hepatocytes transplanted in rats. In: Proceedings of the National Academy of Sciences of the United States of America. 1986 ; Vol. 83, No. 19. pp. 7475-7479.
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AU - Demetriou, A. A.

AU - Levenson, S. M.

AU - Novikoff, P. M.

AU - Chowdhury, N. R.

AU - Whiting, J.

AU - Reisner, A.

AU - Roy-Chowdhury, Jayanta

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