Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold

Autor: Soon Seng, Ng, Kourosh, Saeb-Parsy, Samuel J I, Blackford, Joe M, Segal, Maria Paola, Serra, Marta, Horcas-Lopez, Da Yoon, No, Sotiris, Mastoridis, Wayel, Jassem, Curtis W, Frank, Nam Joon, Cho, Hiromitsu, Nakauchi, Jeffrey S, Glenn, S Tamir, Rashid
Rok vydání: 2018
Předmět:
Organogenesis
Biomimetic materials
CLF
cholyl-lysyl-flourescence
Biocompatible Materials
IH
iPSC derived hepatic progenitors
ECAM
epithelial cell adhesion molecule
HUVEC
human umbilical endothelial cell
MSC
mesenchymal stem cell
HSGP
heparin sulfate glycoprotein
Polyethylene Glycols
CLDN1
claudin 1
2D
two-dimensional
TGFβ
transforming growth factor beta
DE
iPSC derived definitive endoderm
Cells
Cultured
Liver stem cells
AFP
alpha-fetoprotein
HNF4a
hepatocyte nuclear factor 4-alpha
Tissue Scaffolds
RNA-seq
RNA-sequence
ZO-1
tight junction protein 1
TGZ
Troglitazone
ICC
inverted colloidal crystal
OCLN
occludin
ECM
extracellular matrix
Organoids
ASGR1
asialoglycoprotein receptor 1
Liver
BSEP
bile-salt efflux pump
HCV
hepatitis C virus
LDLR
low-density lipoprotein receptor
H&E
haematoxylin and eosin
CYC
cyclopamine
Crystallization
SCARB1
scavenger receptor class B type 1
iPSC
induced pluripotent stem cell
Induced Pluripotent Stem Cells
Ln
laminin
Bioengineering
RT-qPCR
reverse transcription-quantitative polymerase chain reaction
Article
CK19
keratin 19
MRP2
multidrug resistance protein 1
Humans
ALB
albumin
PEG
polyethylene glycol
Tissue Engineering
3D
three-dimensional
Col
collagen
PCA
principle component analysis
FDA
food and drug administration
Fn
fibronectin
Zdroj: Biomaterials
ISSN: 1878-5905
Popis: Generation of human organoids from induced pluripotent stem cells (iPSCs) offers exciting possibilities for developmental biology, disease modelling and cell therapy. Significant advances towards those goals have been hampered by dependence on animal derived matrices (e.g. Matrigel), immortalized cell lines and resultant structures that are difficult to control or scale. To address these challenges, we aimed to develop a fully defined liver organoid platform using inverted colloid crystal (ICC) whose 3-dimensional mechanical properties could be engineered to recapitulate the extracellular niche sensed by hepatic progenitors during human development. iPSC derived hepatic progenitors (IH) formed organoids most optimally in ICC scaffolds constructed with 140 μm diameter pores coated with type I collagen in a two-step process mimicking liver bud formation. The resultant organoids were closer to adult tissue, compared to 2D and 3D controls, with respect to morphology, gene expression, protein secretion, drug metabolism and viral infection and could integrate, vascularise and function following implantation into livers of immune-deficient mice. Preliminary interrogation of the underpinning mechanisms highlighted the importance of TGFβ and hedgehog signalling pathways. The combination of functional relevance with tuneable mechanical properties leads us to propose this bioengineered platform to be ideally suited for a range of future mechanistic and clinical organoid related applications.
Databáze: OpenAIRE
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