Regulation of hepatic differentiation of human embryonic stem cells by calcium silicate extracts for liver injury repairing

Zheng, Lu; Lü, Dongyuan; Zhang, Fan; Xing, Min; Wang, Xiaoya; Jia, Xiaohua; Shu, Xinyu; Li, Peiwen; Lü, Shouqin; Chang, Jiang; Long, Mian

doi:10.1016/j.apmt.2020.100730

Cited by 5 publications

(5 citation statements)

References 76 publications

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“…Treating different sources of MSCs (BMMSCs, or UMSCs) with HGF and oncostatin could improve the efficiency of SCs differentiation toward the hepatocytes producing ALB, storage glycogen, secretion urea, uptake LDL, and increase cytochrome P450 activity [ 23 ]. Zheng et al found that using the inorganic calcium silicate optimized the ESCs differentiation into functional hepatocyte-like cells [ 24 ]. The other study showed that treating BMSCs with DLL4 (Delta-like ligand 4-mediated Notch activation contributes to reversing biliary injury) efficiently differentiated into Cholangiocytes and restores liver damage [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, it appears that the in vitro treatment of SCs with different factors plays a key role in the improvement of differentiation efficacy and subsequently on the therapeutic outcome. For instance, treating MSCs with plant component such as ginsenosides [ 20 ], inorganic biomaterials such as calcium silicate [ 24 ], growth factors (GFs) such as IGF [ 22 ], or GFs combination (HGF and EGF both in vitro and in vivo investigation) [ 51 ], or (HGF)/oncostatin (cytokine family member) combination [ 23 ] showed a greater differentiation of SCs into hepatocytes and would generate more functional hepatocytes. The other study showed that treating MSC with DLL4 could enhance cholangiocyte differentiation from SCs [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

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The Efficiency of Stem Cells (SCs) Differentiation into Functional Hepatocytes for Treating Liver Disorders: A Systematic Review

Nemati

Ebrahimi

Abolhassani

et al. 2023

BioMed Research International

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Stem cells provided new opportunity to treat various diseases, including liver disorders. Stem cells are unspecialized cells, stimulating influential research interest be indebted to their multipotent self-renewal capacity and differentiation characteristics into several specialized cell types. Many factors contribute to their differentiation into different cell types such as insulin producing cells, osteoblast, and hepatocytes. Accordingly, wide range methods and materials have been used to transform stem cells into hepatocytes, but effectiveness of differentiation is different and depends on several factors such as cell-to-cell adhesion, cell-to-cell contact, and cell biological change. Search was done in PubMed, Scopus, and WOS to evaluate results of studies about stem cells differentiation for higher efficacy. Among more than 28000 papers, 51 studies were considered eligible for more evaluations. Results indicated that most studies were performed on mesenchymal stem cells compared with other types. Acute liver failure was the most investigated liver disorder, and tissue engineering was the most investigated differentiation methods. Also, functional parameters were the most evaluated parameters in assessing differentiation efficacy. We summarize recent advances in increasing efficiency of stem cells differentiation using varied materials, since promising results of this review, further studies are needed to assess efficiency and safety of these cells transplantation in some liver disease treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Efficiency of Stem Cells (SCs) Differentiation into Functional Hepatocytes for Treating Liver Disorders: A Systematic Review

Nemati

Ebrahimi

Abolhassani

et al. 2023

BioMed Research International

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“…To generate HLC from hESC, we adopted a hepatic differentiation protocol reported previously (supplementary figure 1(A)) [15,16,65]. The hepatic differentiation potential of hESC was first examined in 2D-cultured hESC (supplementary figure 1).…”

Section: Hepatic Differentiation Of Hesc and Characterization Of Mcol...mentioning

confidence: 99%

“…To address this, pluripotent stem cells, including human induced pluripotent stem cells and human embryonic stem cells (hESCs), have been induced to differentiate into hepatocytelike cells (HLCs) [12][13][14]. A three-step differentiation protocol mimicking the different stages of liver development (definitive endoderm (DE) differentiation, hepatic specification, and hepatocyte maturation) has been widely used for hepatic differentiation [15,16]. The highly proliferative pluripotent stem cells can yield clinically-relevant amount of HLC for the construction of 3D liver tissue [17].…”

Section: Introductionmentioning

confidence: 99%

Efficient hepatic differentiation of hydrogel microsphere-encapsulated human pluripotent stem cells for engineering prevascularized liver tissue

et al. 2022

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Liver tissue engineering is promising as an alternative strategy to treat liver failure. However, generating functional hepatocytes from stem cells is conventionally restricted by the immature status of differentiated cells. Besides, embedding hepatocytes in bulk scaffold is limited by a lack of vascularity and low cell-packing density. Here, we fabricate collagen type I (COL1) microspheres for efficient hepatic differentiation of pluripotent stem cells and subsequent assembly of prevascularized liver tissue (PLT). Using a microfluidic platform, we demonstrate that hydrogel microspheres (mCOL1) encapsulating human embryonic stem cells (hESC) can be reproducibly generated and efficiently differentiated into hepatocyte-like cells (HLC) microspheres for the first time. Compared with other culture configurations such as encapsulation of hESC in a bulk COL1 hydrogel and 2D monolayer culture, COL1 microspheres with high uniformity produce HLC microspheres of improved maturity based on comprehensive analyses of cell morphology, transcriptome profile, hepatic marker expression and hepatic functions. In addition, these HLC microspheres can be applied as building blocks to self-assemble with endothelial cells to construct a dense PLT. The PLT resembles native liver tissue with high cell-packing density, shows successful engraftment in mice liver following implantation, and exhibits improved hepatic function in vivo. Overall, it is believed that this multiscale technology will advance the fabrication of stem cell-based liver tissue for regenerative medicine, drug screening, and in vitro liver modeling.

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“…Hepatic differentiation is a complex process that involves four distinct stages for stem cells (stemness maintenance (STEM), de nitive endodermal lineage (DE), precursor hepatocytes (Pre-H), and hepatocytelike cells (M-H)), each characterized by speci c cellular and molecular changes 11 . The key markers associated with the stem stage include OCT-4 and NANOG; at the DE stage, the two DE biomarkers SOX17 and CXCR4 were sound expression; the critical markers associated with Pre-H stage are AFP and SOX9; at the M-H stage, the two hepatic biomarkers ALB and CK18 were uniformly distributed inside the cells and presented over the entire cells 11,12 . Because Human hepatic stem cells are relatively di cult to obtain and their growth and differentiation rates are much slower in cell culture conditions, other cell lines were often alternatively used to study the differentiation process of human hepatic stem cells.…”

Section: Introductionmentioning

confidence: 99%

TRPML1 ion channel promote HepaRG cells differentiation under simulated microgravity conditions

Gao,

Fan,

Lü

et al. 2023

Preprint

Self Cite

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Stem cell differentiation must be regulated by intricate and complex interactions between cells and their surrounding environment, ensuring normal organ and tissue morphology such as the liver 1. Though it is well acknowledged that microgravity provides necessary mechanical force signals for cells fate 2, how microgravity affects growth, differentiation, and communication is still largely unknown due to the lack of real experimental scenarios and reproducibility tools. Here, we used Rotating Flat Chamber (RFC) to simulate ground-based microgravity effects to study how microgravity affects the differentiation of HepaRG (hepatic progenitor cells) cells. Unexpectedly, we found that simulated microgravity could promote HepaRG cells differentiation which was exhibited as increased expression of Alpha-fetoprotein (AFP), albumin (ALB), and Recombinant Cytokeratin 18 (CK18). Through screening a series of mechanical receptors, we identified that ion channel TRPML1 was critical for the differentiation promotion effect of microgravity. Once TRPML1 was activated by microgravity, the concentration of lysosomal calcium ions was increased to activate the Wnt/β-catenin signaling pathway, which finally led to the enhanced cell differentiation of HepaRG cells. In addition, the cytoskeleton was remodeled under microgravity conditions and then influenced the expression of PI (3,5) P2, which is the best-known activator of TRPML1. In summary, our findings have established a mechanism by which microgravity promotes the differentiation of HepaRG cells through the TRPML1 signaling pathway, which may provide a potential target for the regulation of hepatic stem/progenitor cells differentiation and embryonic liver development under microgravity conditions.

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Regulation of hepatic differentiation of human embryonic stem cells by calcium silicate extracts for liver injury repairing

Cited by 5 publications

References 76 publications

The Efficiency of Stem Cells (SCs) Differentiation into Functional Hepatocytes for Treating Liver Disorders: A Systematic Review

The Efficiency of Stem Cells (SCs) Differentiation into Functional Hepatocytes for Treating Liver Disorders: A Systematic Review

Efficient hepatic differentiation of hydrogel microsphere-encapsulated human pluripotent stem cells for engineering prevascularized liver tissue

TRPML1 ion channel promote HepaRG cells differentiation under simulated microgravity conditions

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