Generation of humanized animal livers using embryoid body-derived stem cell transplant

Jayme E. Locke, Zhao Li Sun, Daniel Warren, Timothy P. Sheets, Horatio Holzer, Michael J. Shamblott, Robert A. Montgomery, Andrew M Cameron

Research output: Contribution to journalArticle

Abstract

Objective: Animal organs engineered to be chimeric for human cells could contribute significantly to the field of transplantation, including studies of human-specific diseases such as hepatitis-C, as treatment for in-born errors of metabolism, and for development of a renewable source of transplantable organs via modified xenotransplantation. We sought to use human embryoid body-derived stem cells (EBDs) to populate livers in animals for applications in transplant surgery. Methods: SCID mice and rats underwent liver injury with carbon tetrachloride exposure or partial hepatectomy. Animals received intrasplenic injection of fluorescently labeled human stem cells. Spleen and liver were assessed at 2, 7, 15, and 30 days after transplant for the presence of EBDs and markers of human hepatocyte differentiation. Results: EBDs migrate to and engraft in animal liver after splenic injection under conditions of hepatic injury. EBDs are detectable at 2 days and are in abundance at 1 week after transplant. EBDs persist in rodent liver long term (>1 month), and once engrafted differentiate into functional human hepatocytes as assessed by production of human alpha-feto-protein (AFP) and human albumin. Conclusions: We developed a novel animal model in which hepatic injury and stem cell transplantation lead to the generation of humanized animal organs. We are currently using our model to study recurrent hepatitis-C after liver transplantation, and as an alternative to whole organ transplantation for treatment of in-born errors of metabolism.

Original languageEnglish (US)
Pages (from-to)487-491
Number of pages5
JournalAnnals of Surgery
Volume248
Issue number3
DOIs
StatePublished - Sep 2008

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Embryoid Bodies
Stem Cells
Transplants
Liver
Animal Structures
Hepatocytes
Hepatitis C
Wounds and Injuries
Heterologous Transplantation
Injections
SCID Mice
Carbon Tetrachloride
Hepatectomy
Stem Cell Transplantation
Organ Transplantation
Human Body
Liver Transplantation
Rodentia
Spleen
Animal Models

ASJC Scopus subject areas

  • Surgery

Cite this

Generation of humanized animal livers using embryoid body-derived stem cell transplant. / Locke, Jayme E.; Sun, Zhao Li; Warren, Daniel; Sheets, Timothy P.; Holzer, Horatio; Shamblott, Michael J.; Montgomery, Robert A.; Cameron, Andrew M.

In: Annals of Surgery, Vol. 248, No. 3, 09.2008, p. 487-491.

Research output: Contribution to journalArticle

Locke, Jayme E. ; Sun, Zhao Li ; Warren, Daniel ; Sheets, Timothy P. ; Holzer, Horatio ; Shamblott, Michael J. ; Montgomery, Robert A. ; Cameron, Andrew M. / Generation of humanized animal livers using embryoid body-derived stem cell transplant. In: Annals of Surgery. 2008 ; Vol. 248, No. 3. pp. 487-491.
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