Functional human and murine tissue-engineered liver is generated from adult stem/progenitor cells

Nirmala Mavila, Andrew Trecartin, Ryan Spurrier, Yi Xiao, Xiaogang Hou, David James, Xiaowei Fu, Brian Truong, Clara Wang, Gerald S. Lipshutz, Kasper S. Wang, Tracy C. Grikscheit

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Liver disease affects large numbers of patients, yet there are limited treatments available to replace absent or ineffective cellular function of this crucial organ. Donor scarcity and the necessity for immunosuppression limit one effective therapy, orthotopic liver transplantation. But in some conditions such as inborn errors of metabolism or transient states of liver insufficiency, patients may be salvaged by providing partial quantities of functional liver tissue. After transplanting multicellular liver organoid units composed of a heterogeneous cellular population that includes adult stem and progenitor cells, both mouse and human tissue-engineered liver (TELi) form in vivo. TELi contains normal liver components such as hepatocytes with albumin expression, CK19-expressing bile ducts and vascular structures with ɑ-smooth muscle actin expression, desmin-expressing stellate cells, and CD31-expressing endothelial cells. At 4weeks, TELi contains proliferating albumin-expressing cells and identification of β2-microglobulin-expressing cells demonstrates that the majority of human TELi is composed of transplanted human cells. Human albumin is detected in the host mouse serum, indicating in vivo secretory function. Liquid chromatography/mass spectrometric analysis of mouse serum after debrisoquine administration is followed by a significant increase in the level of the human metabolite, 4-OH-debrisoquine, which supports the metabolic and xenobiotic capability of human TELi in vivo. Implanted TELi grew in a mouse model of inducible liver failure.

Original languageEnglish (US)
Pages (from-to)238-248
Number of pages11
JournalStem Cells Translational Medicine
Volume6
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Adult Stem Cells
Stem Cells
Liver
Debrisoquin
Albumins
Organoids
Hepatic Insufficiency
Inborn Errors Metabolism
Desmin
Liver Failure
Xenobiotics
Bile Ducts
Serum
Liquid Chromatography
Liver Transplantation
Immunosuppression
Smooth Muscle
Blood Vessels
Liver Diseases
Actins

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology

Cite this

Mavila, N., Trecartin, A., Spurrier, R., Xiao, Y., Hou, X., James, D., ... Grikscheit, T. C. (2017). Functional human and murine tissue-engineered liver is generated from adult stem/progenitor cells. Stem Cells Translational Medicine, 6(1), 238-248. https://doi.org/10.5966/sctm.2016-0205

Functional human and murine tissue-engineered liver is generated from adult stem/progenitor cells. / Mavila, Nirmala; Trecartin, Andrew; Spurrier, Ryan; Xiao, Yi; Hou, Xiaogang; James, David; Fu, Xiaowei; Truong, Brian; Wang, Clara; Lipshutz, Gerald S.; Wang, Kasper S.; Grikscheit, Tracy C.

In: Stem Cells Translational Medicine, Vol. 6, No. 1, 01.01.2017, p. 238-248.

Research output: Contribution to journalArticle

Mavila, N, Trecartin, A, Spurrier, R, Xiao, Y, Hou, X, James, D, Fu, X, Truong, B, Wang, C, Lipshutz, GS, Wang, KS & Grikscheit, TC 2017, 'Functional human and murine tissue-engineered liver is generated from adult stem/progenitor cells', Stem Cells Translational Medicine, vol. 6, no. 1, pp. 238-248. https://doi.org/10.5966/sctm.2016-0205
Mavila, Nirmala ; Trecartin, Andrew ; Spurrier, Ryan ; Xiao, Yi ; Hou, Xiaogang ; James, David ; Fu, Xiaowei ; Truong, Brian ; Wang, Clara ; Lipshutz, Gerald S. ; Wang, Kasper S. ; Grikscheit, Tracy C. / Functional human and murine tissue-engineered liver is generated from adult stem/progenitor cells. In: Stem Cells Translational Medicine. 2017 ; Vol. 6, No. 1. pp. 238-248.
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