Transplantation of a human iPSC-derived hepatocyte sheet increases survival in mice with acute liver failure

Nagamoto, Yasuhito; Takayama, Kazuo; Ohashi, Kazuhiko; Okamoto, Ryota; Sakurai, Fuminori; Tachibana, Masashi; Kono, Kenji; Mizuguchi, Hiroyuki

doi:10.1016/j.jhep.2016.01.004

Cited by 134 publications

(119 citation statements)

References 35 publications

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“…Therefore, hepatocyte‐like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells, which have the potential to self‐replicate and differentiate into almost all types of cells, would be an attractive cell source . Several groups, including us, have developed hepatocyte differentiation technologies from human iPS cells and have demonstrated the therapeutic potential of human iPS‐HLCs against liver failure by using mice models of liver failure . However, the clinical application of human iPS‐HLCs has not been realized because the safety of human iPS‐HLC transplantation has not been sufficiently verified.…”

Section: Introductionmentioning

confidence: 99%

Generation of safe and therapeutically effective human induced pluripotent stem cell‐derived hepatocyte‐like cells for regenerative medicine

Takayama

Akita

Mimura

et al. 2017

Hepatology Communications

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Hepatocyte‐like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells are expected to be applied for regenerative medicine. In this study, we attempted to generate safe and therapeutically effective human iPS‐HLCs for hepatocyte transplantation. First, human iPS‐HLCs were generated from a human leukocyte antigen‐homozygous donor on the assumption that the allogenic transplantation might be carried out. Highly efficient hepatocyte differentiation was performed under a feeder‐free condition using human recombinant laminin 111, laminin 511, and type IV collagen. The percentage of asialoglycoprotein receptor 1‐positive cells was greater than 80%, while the percentage of residual undifferentiated cells was approximately 0.003%. In addition, no teratoma formation was observed even at 16 weeks after human iPS‐HLC transplantation. Furthermore, harmful genetic somatic single‐nucleotide substitutions were not observed during the hepatocyte differentiation process. We also developed a cryopreservation protocol for hepatoblast‐like cells without negatively affecting their hepatocyte differentiation potential by programming the freezing temperature. To evaluate the therapeutic potential of human iPS‐HLCs, these cells (1 × 106 cells/mouse) were intrasplenically transplanted into acute liver injury mice treated with 3 mL/kg CCl4 only once and chronic liver injury mice treated with 0.6 mL/kg CCl4 twice weekly for 8 weeks. By human iPS‐HLC transplantation, the survival rate of the acute liver injury mice was significantly increased and the liver fibrosis level of chronic liver injury mice was significantly decreased. Conclusion: We were able to generate safe and therapeutically effective human iPS‐HLCs for hepatocyte transplantation. (Hepatology Communications 2017;1:1058–1069)

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Section: Introductionmentioning

confidence: 99%

Generation of safe and therapeutically effective human induced pluripotent stem cell‐derived hepatocyte‐like cells for regenerative medicine

Takayama

Akita

Mimura

et al. 2017

Hepatology Communications

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“…There is no ideal single cell marker by which MPCs can be distinguished from other types of cells. Recently Nagamoto et al [28] showed that the transplantation of human iPSC-derived hepatocytes sheets was the advantageous method compared to the conventional intrasplenic cell infusion method. The expression of PCLP1 was observed not only in MCs but also in podocytes.…”

Section: Discussionmentioning

confidence: 99%

Generation of mesothelial progenitor‐like cells from mouse‐induced pluripotent stem cells

Inagaki

Kokudo

et al. 2019

FEBS Letters

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Mesothelial cells, which cover the surface of visceral organs and serous cavities in mammals, play a crucial role in preventing adhesion. We previously reported that primary mesothelial progenitor cells (MPCs) can not only prevent postoperative adhesion but also promote liver regeneration after hepatectomy. Induced pluripotent stem cells (iPSCs) have the potential to be used for regenerative medicine. Here, we have established a differentiation protocol for mouse iPSC‐derived MPCs (miMPCs) via the exposure to defined factors, as well as purification using MPC‐specific cell surface antigens. Furthermore, the miMPCs had the ability to suppress postoperative adhesion and facilitate liver regeneration. This is the first report highlighting the generation of functional miMPCs, which may offer potential for de novo cell therapy.

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“…The results of their study revealed that orthotopic transplantation of their engineered cell‐sheets improved liver regeneration and presented therapeutic impact on acute liver injury ( Figure ). In 2016, Nagamoto et al evaluated the therapeutic potential of human induced pluripotent stems derived hepatocyte‐like cells (iPS‐HLCs) for liver injury. The transplantation of human iPSC‐derived hepatocyte sheets into the mice with carbon tetrachloride‐induced acute liver injury showed that the transplanted sheets ameliorated the lethal acute liver damage.…”

Section: Conventional Versus Advanced Processing Technologies For LIVmentioning

confidence: 99%

Advanced Biomaterials and Processing Methods for Liver Regeneration: State‐of‐the‐Art and Future Trends

Morais

Vieira

Zhao

et al. 2020

Adv Healthcare Materials

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Liver diseases contribute markedly to the global burden of mortality and disease. The limited organ disposal for orthotopic liver transplantation results in a continuing need for alternative strategies. Over the past years, important progress has been made in the field of tissue engineering (TE). Many of the early trials to improve the development of an engineered tissue construct are based on seeding cells onto biomaterial scaffolds. Nowadays, several TE approaches have been developed and are applied to one vital organ: the liver. Essential elements must be considered in liver TE—cells and culturing systems, bioactive agents or growth factors (GF), and biomaterials and processing methods. The potential of hepatocytes, mesenchymal stem cells, and others as cell sources is demonstrated. They need engineered biomaterial‐based scaffolds with perfect biocompatibility and bioactivity to support cell proliferation and hepatic differentiation as well as allowing extracellular matrix deposition and vascularization. Moreover, they require a microenvironment provided using conventional or advanced processing technologies in order to supply oxygen, nutrients, and GF. Herein the biomaterials and the conventional and advanced processing technologies, including cell‐sheets process, 3D bioprinting, and microfluidic systems, as well as the future trends in these major fields are discussed.

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Transplantation of a human iPSC-derived hepatocyte sheet increases survival in mice with acute liver failure

Abstract: Human iPS-HLC sheet transplantation would be a useful and reliable therapeutic approach for a patient with severe liver diseases.

Cited by 134 publications

References 35 publications

Generation of safe and therapeutically effective human induced pluripotent stem cell‐derived hepatocyte‐like cells for regenerative medicine

Generation of safe and therapeutically effective human induced pluripotent stem cell‐derived hepatocyte‐like cells for regenerative medicine

Generation of mesothelial progenitor‐like cells from mouse‐induced pluripotent stem cells

Advanced Biomaterials and Processing Methods for Liver Regeneration: State‐of‐the‐Art and Future Trends

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