Hepatic targeting and biodistribution of human fetal liver stem/progenitor cells and adult hepatocytes in mice

Kang Cheng, Daniel Benten, Kuldeep Bhargava, Mari Inada, Brigid Joseph, Christopher Palestro, Sanjeev Gupta

Research output: Contribution to journalArticle

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Abstract

Tracking stem/progenitor cells through noninvasive imaging is a helpful means of assessing the targeting of transplanted cells to specific organs. We performed in vitro and in vivo studies wherein adult human hepatocytes and human fetal liver stem/progenitor cells were labeled with indium-111 ( 111In)-oxine and technetium-99m (99mTc)-Ultratag or 99mTc-Ceretec. The labeling efficiency and viability of cells was analyzed in vitro, and organ biodistribution of cells was analyzed in vivo after transplantation in xenotolerant nonobese diabetic/severe combined immunodeficiency mice through intrasplenic or intraportal routes. We found that adult hepatocytes and fetal liver stem/progenitor cells incorporated 111In but not 99mTc labels. After radiolabeling, cell viability was unchanged. Transplanted adult hepatocytes or fetal liver stem/progenitor cells were targeted to the liver more effectively by the intraportal rather than the intrasplenic route. Transplanted cells were retained in the liver after intraportal injection and in the liver and spleen after intrasplenic injection, without translocations into pulmonary or systemic circulations. Compared with fetal liver stem/progenitor cells, fewer adult hepatocytes were retained in the spleen after intrasplenic transplantation. The distribution of transplanted cells in organs was substantiated by genetic assays, including polymerase chain reaction amplification of DNA sequences from a primate-specific Charcot-Marie-Tooth element, and in situ hybridization for primate alphoid satellite sequences ubiquitous in all centromeres. Conclusion: 111In labeling of human fetal liver stem/progenitor cells and adult hepatocytes was effective for noninvasive localization of transplanted cells. This should facilitate continued development of cell therapies through further animal and clinical studies.

Original languageEnglish (US)
Pages (from-to)1194-1203
Number of pages10
JournalHepatology
Volume50
Issue number4
DOIs
StatePublished - 2009

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Hepatocytes
Stem Cells
Liver
Primates
Cell Survival
Spleen
Transplantation
Technetium Tc 99m Exametazime
Severe Combined Immunodeficiency
Injections
Centromere
Technetium
Cell- and Tissue-Based Therapy
In Situ Hybridization
Tooth
Polymerase Chain Reaction
Lung

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

Cite this

Hepatic targeting and biodistribution of human fetal liver stem/progenitor cells and adult hepatocytes in mice. / Cheng, Kang; Benten, Daniel; Bhargava, Kuldeep; Inada, Mari; Joseph, Brigid; Palestro, Christopher; Gupta, Sanjeev.

In: Hepatology, Vol. 50, No. 4, 2009, p. 1194-1203.

Research output: Contribution to journalArticle

Cheng, K, Benten, D, Bhargava, K, Inada, M, Joseph, B, Palestro, C & Gupta, S 2009, 'Hepatic targeting and biodistribution of human fetal liver stem/progenitor cells and adult hepatocytes in mice', Hepatology, vol. 50, no. 4, pp. 1194-1203. https://doi.org/10.1002/hep.23120
Cheng, Kang ; Benten, Daniel ; Bhargava, Kuldeep ; Inada, Mari ; Joseph, Brigid ; Palestro, Christopher ; Gupta, Sanjeev. / Hepatic targeting and biodistribution of human fetal liver stem/progenitor cells and adult hepatocytes in mice. In: Hepatology. 2009 ; Vol. 50, No. 4. pp. 1194-1203.
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