Founder cells for hepatocytes during liver regeneration: from identification to application

Wei, Saisai; Tang, Jiancheng; Cai, Xiujun

doi:10.1007/s00018-020-03457-3

Cited by 6 publications

(4 citation statements)

References 84 publications

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“…In their experiments, Faber and colleagues observed mitosis in the small bile ducts and hyperplasia of the oval cells after ethionine diet (Farber, 1956). Subsequent studies suggested that the activity of these progenitor cells were mainly present at the canal of Hering and were involved in bi-potent activity, by replacing both damage hepatocytes and cholangiocytes (Wei et al, 2020). Although there are differences in the phenotypic markers between the HLSCs and oval cells, we can only speculate that HLSCs are a separate niche of stem cells in the liver, since it has not been confirmed in vivo.…”

Section: Hlsc Isolation and Characterizationmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

“…Cell therapy is an alternative form of treatment for liver disease that involves in vitro amplification followed by transplantation of healthy stem/progenitor cells into patients, ideally through a minimally invasive procedure (Wei et al, 2020). Currently, many clinical trials of stem cell-based therapies for liver diseases have been carried out or are ongoing, including MSCs, hematopoietic stem cells, and other bone-marrow derived cells (Wei et al, 2020). Nonetheless, several issues need to be taken into consideration in order to obtain this goal: firstly, it is essential that the cells remain genetically stable and non-tumorigenic as they proliferate; secondly, a sufficient number of healthy cells is required and thirdly, the cells need to maintain their properties under storage conditions.…”

Section: Discussionmentioning

confidence: 99%

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Human Liver Stem Cells: A Liver-Derived Mesenchymal Stromal Cell-Like Population With Pro-regenerative Properties

Bruno¹,

Sanchez²,

Chiabotto³

et al. 2021

Front. Cell Dev. Biol.

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Human liver stem cells (HLSCs) were described for the first time in 2006 as a new stem cell population derived from healthy human livers. Like mesenchymal stromal cells, HLSCs exhibit multipotent and immunomodulatory properties. HLSCs can differentiate into several lineages under defined in vitro conditions, such as mature hepatocytes, osteocytes, endothelial cells, and islet-like cell organoids. Over the years, HLSCs have been shown to contribute to tissue repair and regeneration in different in vivo models, leading to more than five granted patents and over 15 peer reviewed scientific articles elucidating their potential therapeutic role in various experimental pathologies. In addition, HLSCs have recently completed a Phase 1 study evaluating their safety post intrahepatic injection in infants with inherited neonatal onset hyperammonemia. Even though a lot of progress has been made in understanding HLSCs over the past years, some important questions regarding the mechanisms of action remain to be elucidated. Among the mechanisms of interaction of HLSCs with their environment, a paracrine interface has emerged involving extracellular vesicles (EVs) as vehicles for transferring active biological materials. In our group, the EVs derived from HLSCs have been studied in vitro as well as in vivo. Our attention has mainly been focused on understanding the in vivo ability of HLSC–derived EVs as modulators of tissue regeneration, inflammation, fibrosis, and tumor growth. This review article aims to discuss in detail the role of HLSCs and HLSC-EVs in these processes and their possible future therapeutic applications.

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Section: Hlsc Isolation and Characterizationmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Human Liver Stem Cells: A Liver-Derived Mesenchymal Stromal Cell-Like Population With Pro-regenerative Properties

Bruno¹,

Sanchez²,

Chiabotto³

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…The lack of transplantable organs represents one of the most important problems in the field of transplantation, thus the development of regenerative medicine caught the attention of the scientific community. The liver has a high regenerative capability, and, consequently, it is a proper candidate for regenerative therapy [378]. Liver organoids have the capability to imitate hepatocyte regeneration during liver homeostasis, and they are gaining importance in the field of regenerative medicine, being considered as biological alternatives for organ replacement [379].…”

Section: Livermentioning

confidence: 99%

Three-Dimensional Cell Cultures: The Bridge between In Vitro and In Vivo Models

Urzì,

Gasparro,

Costanzo

et al. 2023

IJMS

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Although historically, the traditional bidimensional in vitro cell system has been widely used in research, providing much fundamental information regarding cellular functions and signaling pathways as well as nuclear activities, the simplicity of this system does not fully reflect the heterogeneity and complexity of the in vivo systems. From this arises the need to use animals for experimental research and in vivo testing. Nevertheless, animal use in experimentation presents various aspects of complexity, such as ethical issues, which led Russell and Burch in 1959 to formulate the 3R (Replacement, Reduction, and Refinement) principle, underlying the urgent need to introduce non-animal-based methods in research. Considering this, three-dimensional (3D) models emerged in the scientific community as a bridge between in vitro and in vivo models, allowing for the achievement of cell differentiation and complexity while avoiding the use of animals in experimental research. The purpose of this review is to provide a general overview of the most common methods to establish 3D cell culture and to discuss their promising applications. Three-dimensional cell cultures have been employed as models to study both organ physiology and diseases; moreover, they represent a valuable tool for studying many aspects of cancer. Finally, the possibility of using 3D models for drug screening and regenerative medicine paves the way for the development of new therapeutic opportunities for many diseases.

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Assessment of long-term functional maintenance of primary human hepatocytes to predict drug-induced hepatoxicity in vitro

Chen

Tang

et al. 2021

Arch Toxicol

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Founder cells for hepatocytes during liver regeneration: from identification to application

Cited by 6 publications

References 84 publications

Human Liver Stem Cells: A Liver-Derived Mesenchymal Stromal Cell-Like Population With Pro-regenerative Properties

Human Liver Stem Cells: A Liver-Derived Mesenchymal Stromal Cell-Like Population With Pro-regenerative Properties

Three-Dimensional Cell Cultures: The Bridge between In Vitro and In Vivo Models

Assessment of long-term functional maintenance of primary human hepatocytes to predict drug-induced hepatoxicity in vitro

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