Induced pluripotent stem cell-derived hepatocytes and endothelial cells in multi-component hydrogel fibers for liver tissue engineering

Du, Chan; Narayanan, Karthikeyan; Leong, Meng Fatt; Wan, Andrew C.A.

doi:10.1016/j.biomaterials.2014.04.011

Cited by 128 publications

(84 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S5) are important in controlling the quality and purity of hiPSC-HPCs for the bioprinting process and thus the functional performance of the model. Moreover, future study on the mesenchymal to epithelial transition process, which is omitted by many current hepatic differentiation protocols (7,8,12,13), can be carried out to understand, in depth, the differentiation from HPCs to more mature hepatic epithelia. When assessing the albumin production levels of hiPSC-HPCs and HLCs following GelMA encapsulation, the higher magnitude and more sustained level of albumin produced following the peak by HPCs supported their potential to be better candidates for the 3D hydrogel encapsulation.…”

Section: Discussionmentioning

confidence: 99%

“…hiPSC-derived hepatic cells, despite their potential to have malignant transformation following in vivo transplantations, have been widely recognized as the most promising candidate for developing patient-specific human hepatic models in vitro (4,7). Current in vitro liver models using hiPSC-derived hepatic cells are largely limited by their lack of biomimicry (3,7,(10)(11)(12)(13)(14). The 3D triculture model presented here highlights the successful application of DLP-based bioprinting technology to liver tissue engineering and thus the progress of the field to a level where the complex liver microarchitecture and cell composition can be studied in a physiologically relevant model.…”

Section: Discussionmentioning

confidence: 99%

“…Cells at both hepatic progenitor and maturation stages, i.e., HPCs and HLCs, respectively, have demonstrated their potentials in organizing into vascularized liver buds (11,13) and in the construction of in vitro models with simple geometry (10,12,14). To determine the stage of cells along the differentiation pathway that is more suitable for hydrogel encapsulation, HPCs and the relatively more mature HLCs were compared in terms of their albumin secretion time course following encapsulation in GelMA (Fig.…”

Section: D Hydrogel Encapsulation At Hepatic Progenitor Stage Demonsmentioning

confidence: 99%

“…Major liver functions are tightly linked to the 3D assembly of hepatocytes with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Current approaches to use HLCs for an in vitro liver model, however, are mostly limited to 2D culture or simple 3D spheroid cultures (3,7,(10)(11)(12)(13)(14). The lack of a biomimetic microenvironment provided from the 3D interactions of parenchymal and nonparenchymal cell types along the hepatic differentiation stages may potentially be one of the limiting factors to functional maturation of the hepatic progenitor cells (HPCs), as well as the functional preservation of HLCs in vitro (15,16).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting

Zhu

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

726

661

View full text Add to dashboard Cite

The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adiposederived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling.3D bioprinting | in vitro hepatic model | iPSC | tissue engineering | biomaterials T he liver plays a critical role in the synthesis of important proteins and the metabolism of xenobiotic; the failure of these functions is closely related to disease development and drug-induced toxicity (1). For these reasons, in vitro liver models have been extensively developed to serve as platforms for pathophysiological studies and as alternatives to animal models in drug screening and hepatotoxicity prediction (2-4). Human primary hepatocytes, considered one of the most mature liver cell sources, lose many liver-specific functions rapidly when cultured in vitro due to the great discrepancies between the native and culture environments (5, 6). In addition, the practical difficulties in obtaining liver biopsy samples from every patient further hinder their use in personalized liver models. Consequently, hepatocytes derived from human induced pluripotent stem cells (hiPSCs), with the potential to be patient specific and easily accessible, have been widely acknowledged as the most promising cell source for developing personalized human hepatic models (4, 7).Many groups have reported monolayer differentiation of hiPSCs into hepatocyte-like cells (HLCs) and their ability to metabolize drugs (7-9). Nevertheless, hiPSC-derived HLCs are still considered immature in terms of many liver-specific gene expressions, functions, and...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: D Hydrogel Encapsulation At Hepatic Progenitor Stage Demonsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting

Zhu

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

726

661

View full text Add to dashboard Cite

show abstract

“…Endothelial cells also secrete vascular endothelial growth factor that can stimulate proliferation and migration of neuronal precursors, and neuronal maturation [167]. Recently, hiPSC-derived hepatocytes and endothelial cells were cocultured to create functional liver tissue [168]. In addition, iPSC-derived neurons are routinely cocultured with astrocytes to promote synapse formation [53,169].…”

Section: Miniature Three-dimensional Tissue Assemblies Called Organoimentioning

confidence: 99%

Advances in Reprogramming-Based Study of Neurologic Disorders

Nityanandam

Baldwin

2015

Stem Cells and Development

View full text Add to dashboard Cite

The technology to convert adult human non-neural cells into neural lineages, through induced pluripotent stem cells (iPSCs), somatic cell nuclear transfer, and direct lineage reprogramming or transdifferentiation has progressed tremendously in recent years. Reprogramming-based approaches aimed at manipulating cellular identity have enormous potential for disease modeling, high-throughput drug screening, cell therapy, and personalized medicine. Human iPSC (hiPSC)-based cellular disease models have provided proof of principle evidence of the validity of this system. However, several challenges remain before patient-specific neurons produced by reprogramming can provide reliable insights into disease mechanisms or be efficiently applied to drug discovery and transplantation therapy. This review will first discuss limitations of currently available reprogramming-based methods in faithfully and reproducibly recapitulating disease pathology. Specifically, we will address issues such as culture heterogeneity, interline and inter-individual variability, and limitations of two-dimensional differentiation paradigms. Second, we will assess recent progress and the future prospects of reprogramming-based neurologic disease modeling. This includes three-dimensional disease modeling, advances in reprogramming technology, prescreening of hiPSCs and creating isogenic disease models using gene editing.

show abstract

Harnessing the Potential of Stem Cells from Different Sources for Tissue Engineering

Murali

Kshirsagar

Hasan

et al. 2017

Tissue Engineering for Artificial Organs

View full text Add to dashboard Cite

Induced pluripotent stem cell-derived hepatocytes and endothelial cells in multi-component hydrogel fibers for liver tissue engineering

Cited by 128 publications

References 53 publications

Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting

Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting

Advances in Reprogramming-Based Study of Neurologic Disorders

Harnessing the Potential of Stem Cells from Different Sources for Tissue Engineering

Contact Info

Product

Resources

About