title: Functional 3D human primary hepatocyte spheroids made by co-culturing hepatocytes from partial hepatectomy specimens and human adipose-derived stem cells.
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.
authors.affiliation: Department of Biomedical Engineering, Korea University, Seoul, Republic of Korea.
authors.forename: Da Yoon
authors.initials: da Y
authors.lastname: No
authors.forename: Seung-A
authors.initials: SA
authors.lastname: Lee
authors.forename: Yoon Young
authors.initials: YY
authors.lastname: Choi
authors.forename: DoYeun
authors.initials: D
authors.lastname: Park
authors.forename: Ju Yun
authors.initials: JY
authors.lastname: Jang
authors.forename: Dong-Sik
authors.initials: DS
authors.lastname: Kim
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D054338:Cell Transdifferentiation / Q000502:physiology; D018920:Coculture Techniques; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D018874:Spheroids, Cellular / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*