Generation of Functional Hepatic Cells from Pluripotent Stem Cells

Han, ShouWei; Bourdon, Alice; Hamou, Wissam; Dziedzic, Noelle; Goldman, Orit; Gouon-Evans, Valérie

doi:10.4172/2157-7633.s10-008

Cited by 21 publications

(24 citation statements)

References 133 publications

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“…3). A number of protocols have been established to produce hepatocyte-like cells from both human ESCs and iPSCs [45]. The initial step of generating with the phenotype of definitive endoderm has turned out to be crucial in hepatocyte differentiation.…”

Section: Pluripotent Stem Cells For Disease Modeling and Regenerativementioning

confidence: 99%

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Induced Pluripotent Stem Cells as a Source of Hepatocytes

et al. 2014

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During the past decade, a series of discoveries has established the potential of the so called terminally differentiated cells to transition to more primitive progenitor cells. The dramatic demonstration of the ability to reprogram differentiated somatic cells to induced pluripotent stem cells (iPSC) that can then give rise to cells of all three germ layers has opened the possibility of generating virtually any cell type in culture, from any given individual. Taking advantage of these concepts, researchers have generated iPSCs by reprogramming a wide variety of somatic cells. In addition to their practical implications, these studies have provided crucial insights into the mechanism of cell plasticity that underlies the transition from one cell type to another. Using concepts derived from research on embryological development, investigators have differentiated iPSCs to cells resembling hepatocytes in many ways. Such hepatocyte-like cells could be of enormous value in disease modeling, drug discovery and regenerative medicine. However, the currently available methods do not yield cells that fully reproduce the characteristics of adult primary hepatocytes. Thus generating hepatocytes from iPSCs is very much a work in progress. In addition to chronicling these exciting developments, this review will discuss the emergent new approaches to generating iPSCs, improving their differentiation to hepatocyte-like cells and maintaining the hepatocyte-like cells in culture for longer survival and better function.

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Section: Pluripotent Stem Cells For Disease Modeling and Regenerativementioning

confidence: 99%

“…However, a high quality of primary human hepatocytes needs to be assured for this purpose [61]. For a comprehensive list of cell culture components used by various investigators for the stepwise directed differentiation of iPSCs to hepatocyte-like cells, see the review by Han et al [45]. …”

Section: Pluripotent Stem Cells For Disease Modeling and Regenerativementioning

confidence: 99%

Induced Pluripotent Stem Cells as a Source of Hepatocytes

et al. 2014

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“…The use of a specific pool of cytokines in a serumfree medium is a prerequisite for liver organogenesis step in differentiation process (23). For example, high doses of activin A are widely used for endodermal induction in human pluripotent stem cells (24,25).…”

Section: Cytokines and Growth Factorsmentioning

confidence: 99%

Reprogrammed Cell?based Therapy for Liver Disease: From Lab to Clinic

Mehdizadeh

Darabi

2017

jrenhep

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A large number of patients are affected by liver dysfunction worldwide. Liver transplantation is the only efficient treatment in a variety of enduring liver disorders including inherent and end-stage liver diseases. The generation of human functional hepatocytes in high quantities for liver cell therapy is an important goal for ongoing therapies in regenerative medicine. Reprogrammed cells are considered as a promising and unlimited source of hepatocytes, mainly because of their expected lack of immunogenicity and minimized ethical concerns in clinical applications. Despite gained advances in the reprogramming of somatic cells to functional hepatocytes in vitro, production of primary adult hepatocytes that can proliferate in vivo still remains inaccessible. As part of efforts toward translation of cell reprogramming science into clinical practice, more careful cell selection strategies should be integrated into improvement of dedifferentiation and redifferentiation protocols, especially in precision medicine where gene correction is needed. Furthermore, advances in cellular reprogramming highlight the need for developing and evaluating novel standards addressing clinical research interests in this field.

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“…Hepatocytes derived from human pluripotent stem cell (hPSC) differentiation cultures could provide an unlimited supply for cell replacement therapy. However, generation of mature functional cells from these stem cells remains a challenge 1 . Better understanding of the early molecular mechanisms regulating normal liver development could help optimize the generation of functional hPSC-derived hepatic cells.…”

mentioning

confidence: 99%