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Methylcellulose as a scaffold for the establishment of liver-organoids for the potential of treating acute live failure

Research output: Contribution to journalArticle

Anil Chandrashekran, Ragai Mitry, Tharindu Premachandra, Chris Starling, Sharon Lehec, Valeria Iansante, Emer Catherine Fitzpatrick, Celine Fillipi, Maesha Deheragoda, David Hay, Anil Dhawan

Original languageEnglish
Pages (from-to)1087-1104
JournalCell and Gene Therapy Insights
DOIs
Accepted/In press31 Oct 2018
Published2018

Documents

  • Organoid paper V8-revised-1

    Organoid_paper_V8_revised_1.docx, 87.7 KB, application/vnd.openxmlformats-officedocument.wordprocessingml.document

    Uploaded date:08 Nov 2018

  • organoid-fig-v-5-rev

    organoid_fig_v_5_rev.pptx, 8.57 MB, application/octet-stream

    Uploaded date:08 Nov 2018

  • Organoid paper V8-revised-peer-rev-ammend

    Organoid_paper_V8_revised_peer_rev_ammend.docx, 92.3 KB, application/vnd.openxmlformats-officedocument.wordprocessingml.document

    Uploaded date:08 Nov 2018

King's Authors

Abstract

Much progress has been made in understanding the development of human organs through advanced cellular and molecular techniques. Acute liver failure (ALF) in children is a life-threatening condition that relies on liver or hepatocyte transplantation. The translation of novel regenerative medicine strategies for the treatment of ALF is however somewhat limited. Here, we show that in vitro liver-organoids derived from human umbilical cord derived mesenchymal stem cells and human cadaveric donor-derived hepatocytes, cultured in a clinically appropriate manner, exhibit liver function. We obtained organoids that varied in size and morphology which produced albumin, and detoxified ammonium chloride into urea. Immunohistochemistry of these organoids revealed hepatocyte specific, non-parenchymal markers and histological organisation. Our in vitro findings indicate that these organoids may be a useful bridge in ALF while awaiting liver recovery or transplant. The organoid culture system we have established here is also well suited to drug screening and disease modeling.

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