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Tissue Eng Part A. 2018 Apr;24(7-8):576-583. doi: 10.1089/ten.TEA.2017.0161. Epub 2018 Jan 16.

Three-Dimensional Bioprinting of Hepatic Structures with Directly Converted Hepatocyte-Like Cells.

Kang K1,2,3, Kim Y1,2,3, Jeon H2,3, Lee SB4, Kim JS5, Park SA6, Kim WD6, Yang HM7, Kim SJ7, Jeong J2,3, Choi D1,2,3.

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1 Department of Translational Medicine, Graduate School of Biomedical Science and Engineering , Seongdong-gu, Korea.
2 Department of Surgery, Hanyang University College of Medicine , Seoul, Korea.
3 HY Indang Center of Regenerative Medicine and Stem Cell Research, Hanyang University , Seoul, Korea.
4 Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Science (KIRAMS) , Seoul, Korea.
5 Department of Pathology, Hanyang University College of Medicine , Seoul, Korea.
6 Department of Nature-Inspired Nanoconvergence Systems, Korea Institute of Machinery and Materials , Daejeon, Korea.
7 Department of Surgery, Sungkunkwan University College of Medicine , Seoul, Korea.


Three-dimensional (3D) bioprinting technology is a promising new technology in the field of bioartificial organ generation with regard to overcoming the limitations of organ supply. The cell source for bioprinting is very important. Here, we generated 3D hepatic scaffold with mouse-induced hepatocyte-like cells (miHeps), and investigated whether their function was improved after transplantation in vivo. To generate miHeps, mouse embryonic fibroblasts (MEFs) were transformed with pMX retroviruses individually expressing hepatic transcription factors Hnf4a and Foxa3. After 8-10 days, MEFs formed rapidly growing hepatocyte-like colonies. For 3D bioprinting, miHeps were mixed with a 3% alginate hydrogel and extruded by nozzle pressure. After 7 days, they were transplanted into the omentum of Jo2-treated NOD Scid gamma (NSG) mice as a liver damage model. Real-time polymerase chain reaction and immunofluorescence analyses were conducted to evaluate hepatic function. The 3D bioprinted hepatic scaffold (25 × 25 mm) expressed Albumin, and ASGR1 and HNF4a expression gradually increased for 28 days in vitro. When transplanted in vivo, the cells in the hepatic scaffold grew more and exhibited higher Albumin expression than in vitro scaffold. Therefore, combining 3D bioprinting with direct conversion technology appears to be an effective option for liver therapy.


3D bioprinting; cell transplantation; direct conversion; miHep cells

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