Long-term culture of human liver tissue with advanced hepatic functions

Ng, Soon Seng; Xiong, Ai‐Sheng; Nguyen, Khanh Cong; Masek, Anna; No, Da Yoon; Elazar, Menashe; Shteyer, Eyal; Winters, Mark A.; Voedisch, Amy; Shaw, Kate A.; Rashid, S. Tamir; Frank, Curtis W.; Cho, Nam‐Joon; Glenn, Jeffrey S.

doi:10.1172/jci.insight.90853

Cited by 27 publications

(27 citation statements)

References 40 publications

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“…We used a 3D macroporous PEG‐DA hydrogel, known as an inverse colloidal crystal (ICC) scaffold, that aims to mimic the anatomy of native liver tissue. The ICC scaffold has uniform sized pores, interconnected in a hexagonal pattern, and we have previously demonstrated the generation of liver organoids using both primary human fetal liver cells and non‐cGMP‐compliant hPSCs within this model. To facilitate the characterization of the morphogenic transformation of hPSC‐Heps within this scaffold, we performed a series of immunofluorescence staining and constructed the 3D images using confocal microscopy.…”

Section: Resultsmentioning

confidence: 99%

Validation of Current Good Manufacturing Practice Compliant Human Pluripotent Stem Cell-Derived Hepatocytes for Cell-Based Therapy

Blackford

Segal

et al. 2018

Stem Cells Translational Medicine

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Recent advancements in the production of hepatocytes from human pluripotent stem cells (hPSC‐Heps) afford tremendous possibilities for treatment of patients with liver disease. Validated current good manufacturing practice (cGMP) lines are an essential prerequisite for such applications but have only recently been established. Whether such cGMP lines are capable of hepatic differentiation is not known. To address this knowledge gap, we examined the proficiency of three recently derived cGMP lines (two hiPSC and one hESC) to differentiate into hepatocytes and their suitability for therapy. hPSC‐Heps generated using a chemically defined four‐step hepatic differentiation protocol uniformly demonstrated highly reproducible phenotypes and functionality. Seeding into a 3D poly(ethylene glycol)‐diacrylate fabricated inverted colloid crystal scaffold converted these immature progenitors into more advanced hepatic tissue structures. Hepatic constructs could also be successfully encapsulated into the immune‐privileged material alginate and remained viable as well as functional upon transplantation into immune competent mice. This is the first report we are aware of demonstrating cGMP‐compliant hPSCs can generate cells with advanced hepatic function potentially suitable for future therapeutic applications. stem cells translational medicine 2019;8:124&14

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Section: Resultsmentioning

confidence: 99%

Validation of Current Good Manufacturing Practice Compliant Human Pluripotent Stem Cell-Derived Hepatocytes for Cell-Based Therapy

Blackford

Segal

et al. 2018

Stem Cells Translational Medicine

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“…The undegradable PEG hydrogel was applied for the encapsulation of co-cultured hepatocytes, preventing aggregation and overgrowth, and enabling formation of microtissues with stable hepatic function [149]. Recently, PEG was fabricated into 3D hexagonally arrayed lobular human liver tissues and the hydrogel enabled primary human fetal liver cells to self-assemble into a 3D configuration and preserved advanced hepatic functions for at least five months [150].…”

Section: Synthetic Hydrogelsmentioning

confidence: 99%

Bioengineering Liver Transplantation

2019

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“…We utilized a 3D macroporous PEG-DA hydrogel, known as an inverse colloidal crystal (ICC) scaffold, that aims to mimic the anatomy of native liver tissue. The ICC scaffold has uniform sized pores, interconnected in a hexagonal pattern, and 16 we have previously demonstrated that human fetal liver-derived organoids can be generated through their culture within this model [52]. To facilitate the characterization of the morphogenic transformation of hPSC-Heps within this scaffold, we performed a series of immunofluorescence staining and constructed the 3D images using confocal microscopy.…”

Section: D Maturation Of Hpsc-heps Within a Peg-da-based Scaffold Sumentioning

confidence: 99%

Validation of a library of cGMP-compliant human pluripotent stem cell lines for use in liver therapy

Blackford

Segal

et al. 2018

Preprint

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DisclaimersThe authors declare that there is no conflict of interest regarding the publication of this article Acknowledgments of Grants SJIB is supported by a GSTT BRC PhD award STR is supported by an MRC Clinician Scientist Award (MGSBACR) AbstractRecent advancements in the production of hepatocytes from human pluripotent stem cells (hPSC-Heps) afford tremendous possibilities for treatment of patients with liver disease.Validated current good manufacturing practice (cGMP) lines are an essential prerequisite for such applications but have only recently been established. Whether such cGMP lines are capable of hepatic differentiation is not known. To address this knowledge gap, we examined the proficiency of three recently derived cGMP lines (two hiPSC and one hESC) to differentiate into hepatocytes and their suitability for therapy. hPSC-Heps generated using a chemically defined four-step hepatic differentiation protocol uniformly demonstrated highly reproducible phenotypes and functionality. Seeding into a 3D PEG-DA fabricated inverted colloid crystal (ICC) scaffold converted these immature progenitors into more advanced hepatic tissue structures. Hepatic constructs could also be successfully encapsulated into the immune-privileged material alginate. This is the first report we are aware of demonstrating cGMP-compliant hPSCs can generate cells with advanced hepatic function potentially suitable for future therapeutic applications.

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Long-term culture of human liver tissue with advanced hepatic functions

Cited by 27 publications

References 40 publications

Validation of Current Good Manufacturing Practice Compliant Human Pluripotent Stem Cell-Derived Hepatocytes for Cell-Based Therapy

Validation of Current Good Manufacturing Practice Compliant Human Pluripotent Stem Cell-Derived Hepatocytes for Cell-Based Therapy

Bioengineering Liver Transplantation

Validation of a library of cGMP-compliant human pluripotent stem cell lines for use in liver therapy

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