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Transplantation of ahuman iPSC-derivedhepatocyte sheetincreases survival inmice with acute liverfailure Yasuhito NagamotoKazuo TakayamaKazuo Ohashi2016 год

Transplantation of a human iPSC-derived hepatocyte sheet increases survival in mice with acute liver failure
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Аннотация:

Background & Aims

Hepatocyte transplantation is one of the most attractive approaches for the treatment of patients with liver failure. Because human induced pluripotent stem cell-derived hepatocyte-like cells (iPS-HLCs) can be produced on a large scale and generated from a patient with liver failure, they are expected to be used for hepatocyte transplantation. However, when using conventional transplantation methods, i.e., intrasplenic or portal venous infusion, it is difficult to control the engraftment efficiency and avoid unexpected engraftment in other organs because the transplanted cells are delivered into blood circulation before their liver engraftment.

Methods

In this study, to resolve these issues, we attempted to employ a cell sheet engineering technology for experimental hepatocyte transplantation. The human iPS-HLC sheets were attached onto the liver surfaces of mice with liver injury.

Results

This method reduced unexpected engraftment in organs other than the liver compared to that by intrasplenic transplantation. Human albumin levels in the mice with human iPS-HLC sheets were significantly higher than those in the intrasplenically-transplanted mice, suggesting the high potential for cell engraftment of the sheet transplantation procedure. In addition, human iPS-HLC sheet transplantation successfully ameliorated lethal acute liver injury induced by the infusion of carbon tetrachloride (CCl4). Moreover, we found that the hepatocyte growth factor secreted from the human iPS-HLC sheet played an important role in rescuing of mice from acute hepatic failure.

Conclusions

Human iPS-HLC sheet transplantation would be a useful and reliable therapeutic approach for a patient with severe liver diseases.
Год издания: 2016
Авторы: Yasuhito Nagamoto, Kazuo Takayama, Kazuo Ohashi, Ryota Okamoto, Fuminori Sakurai, Masashi Tachibana, Kenji Kawabata, Hiroyuki Mizuguchi
Издательство: Elsevier BV
Источник: Journal of Hepatology
Ключевые слова: Pluripotent Stem Cells Research, Liver physiology and pathology, Organ Transplantation Techniques and Outcomes
Другие ссылки: Journal of Hepatology (PDF)
Journal of Hepatology (HTML)
PubMed (HTML)