Functional 3D Human Primary Hepatocyte Spheroids Made by Co-Culturing Hepatocytes from Partial Hepatectomy Specimens and Human Adipose-Derived Stem Cells

Da Yoon No, Seung A. Lee, Yoon Young Choi, DoYeun Park, Ju Yun Jang, Dong-Sik Kim, Sang Hoon Lee, Rajasingh Johnson

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

We have generated human hepatocyte spheroids with uniform size and shape by co-culturing 1:1 mixtures of primary human hepatocytes (hHeps) from partial hepatectomy specimens and human adipose-derived stem cells (hADSCs) in concave microwells. The hADSCs in spheroids could compensate for the low viability and improve the functional maintenance of hHeps. Co-cultured spheroids aggregated and formed compact spheroidal shapes more rapidly, and with a significantly higher viability than mono-cultured spheroids. The liver-specific functions of co-cultured spheroids were greater, although they contained half the number of hepatocytes as mono-cultured spheroids. Albumin secretion by co-cultured spheroids was 10% higher on day 7, whereas urea secretion was similar, compared with mono-cultured spheroids. A quantitative cytochrome P450 assay showed that the enzymatic activity of co-cultured spheroids cultured for 9 days was 28% higher than that of mono-cultured spheroids. These effects may be due to the transdifferentiation potential and paracrine healing effects of hADSCs on hHeps. These co-cultured spheroids may be useful for creating artificial three-dimensional hepatic tissue constructs and for cell therapy with limited numbers of human hepatocytes.

Original languageEnglish
Article numbere50723
JournalPLoS One
Volume7
Issue number12
DOIs
Publication statusPublished - 2012 Dec 7

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Hepatectomy
Stem cells
hepatocytes
stem cells
Hepatocytes
Stem Cells
viability
secretion
Liver
Cytochrome P-450 Enzyme System
liver
Urea
Albumins
Assays
Enzyme Assays
Cell- and Tissue-Based Therapy
cytochrome P-450
Tissue
albumins
urea

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Functional 3D Human Primary Hepatocyte Spheroids Made by Co-Culturing Hepatocytes from Partial Hepatectomy Specimens and Human Adipose-Derived Stem Cells. / No, Da Yoon; Lee, Seung A.; Choi, Yoon Young; Park, DoYeun; Jang, Ju Yun; Kim, Dong-Sik; Lee, Sang Hoon; Johnson, Rajasingh.

In: PLoS One, Vol. 7, No. 12, e50723, 07.12.2012.

Research output: Contribution to journalArticle

No, Da Yoon ; Lee, Seung A. ; Choi, Yoon Young ; Park, DoYeun ; Jang, Ju Yun ; Kim, Dong-Sik ; Lee, Sang Hoon ; Johnson, Rajasingh. / Functional 3D Human Primary Hepatocyte Spheroids Made by Co-Culturing Hepatocytes from Partial Hepatectomy Specimens and Human Adipose-Derived Stem Cells. In: PLoS One. 2012 ; Vol. 7, No. 12.
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