Isolation and characterization of a novel population of progenitor cells from unmanipulated rat liver

M. Behnan Sahin, Robert E. Schwartz, Shannon M. Buckley, Yves Heremans, Lucas Chase, Wei Shou Hu, Catherine M. Verfaillie

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Widespread use of liver transplantation in the treatment of hepatic diseases is restricted by the limited availability of donated organs. One potential solution to this problem would be isolation and propagation of liver progenitor cells or stem cells. Here, we report on the isolation of a novel progenitor cell population from unmanipulated (that is, no prior exposure to chemicals and no injury) adult rat liver. Rat liver cells were cultured following a protocol developed in our laboratory to generate a unique progenitor cell population called liver-derived progenitor cells (LDPCs). LDPCs were analyzed by fluorescence-activated cell sorting, real-time polymerase chain reaction (RT-PCR), immunostaining and microarray gene expression. LDPCs were also differentiated into hepatocytes and biliary epithelium in vitro and examined for mature hepatic markers and urea and albumin production. These analyses showed that, LDPCs expressed stem cell markers such as cluster domain (CD)45, CD34, c-kit, and Thy 1, similar to hematopoietic stem cells, as well as endodermal/hepatic markers such as hepatocyte nuclear factor (HNF)3β, hematopoietically-expressed homeobox gene-1, c-met, and transthyretin. LDPCs were negative for OV-6, cytokeratins (CKs), albumin, and HNF1α. The microarray gene expression profile demonstrated that they showed some similarities to known liver progenitor/stem cells such as oval cells. In addition, LDPCs differentiated into functional hepatocytes in vitro as shown by albumin expression and urea production. In conclusion, LDPCs are a population of unique liver progenitors that can be generated from unmanipulated adult liver, which makes them potentially useful for clinical applications, especially for cell transplantation in the treatment of liver diseases.

Original languageEnglish (US)
Pages (from-to)333-345
Number of pages13
JournalLiver Transplantation
Volume14
Issue number3
DOIs
StatePublished - Mar 1 2008

Fingerprint

Stem Cells
Liver
Population
Albumins
Urea
Hepatocytes
Hepatocyte Nuclear Factors
Keratin-6
Prealbumin
Homeobox Genes
Cell Transplantation
Hematopoietic Stem Cells
Transcriptome
Liver Transplantation
Liver Diseases
Real-Time Polymerase Chain Reaction
Cultured Cells
Flow Cytometry
Epithelium
Gene Expression

ASJC Scopus subject areas

  • Surgery
  • Hepatology
  • Transplantation

Cite this

Sahin, M. B., Schwartz, R. E., Buckley, S. M., Heremans, Y., Chase, L., Hu, W. S., & Verfaillie, C. M. (2008). Isolation and characterization of a novel population of progenitor cells from unmanipulated rat liver. Liver Transplantation, 14(3), 333-345. https://doi.org/10.1002/lt.21380

Isolation and characterization of a novel population of progenitor cells from unmanipulated rat liver. / Sahin, M. Behnan; Schwartz, Robert E.; Buckley, Shannon M.; Heremans, Yves; Chase, Lucas; Hu, Wei Shou; Verfaillie, Catherine M.

In: Liver Transplantation, Vol. 14, No. 3, 01.03.2008, p. 333-345.

Research output: Contribution to journalArticle

Sahin, MB, Schwartz, RE, Buckley, SM, Heremans, Y, Chase, L, Hu, WS & Verfaillie, CM 2008, 'Isolation and characterization of a novel population of progenitor cells from unmanipulated rat liver', Liver Transplantation, vol. 14, no. 3, pp. 333-345. https://doi.org/10.1002/lt.21380
Sahin, M. Behnan ; Schwartz, Robert E. ; Buckley, Shannon M. ; Heremans, Yves ; Chase, Lucas ; Hu, Wei Shou ; Verfaillie, Catherine M. / Isolation and characterization of a novel population of progenitor cells from unmanipulated rat liver. In: Liver Transplantation. 2008 ; Vol. 14, No. 3. pp. 333-345.
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