Decellularized liver extracellular matrix for iPSC-based liver engineering

Engineered liver grafts for transplantation with sufficient hepatic function have been developed both in small and large animal models using the whole liver engineering approach. However, repopulation of the bile ducts in the whole liver scaffolds has not been addressed yet. In this study, we show the feasibility of repopulating the bile ducts in decellularized rat livers. Biliary epithelial cells were introduced into the bile ducts of the decellularized liver scaffolds with or without hepatocytes in the parenchymal space. The recellularized grafts were cultured under perfusion for up to 2 days and histological analysis revealed that the biliary epithelial cells formed duct-like structures, with the viable hepatocyte mass residing in the parenchymal space, in an arrangement highly comparable to the native tissue. The grafts were viable and functional as confirmed by both albumin and urea assay results and the gene expression analysis of biliary epithelial cells in recellularized liver grafts. This study provides the proof-of-concept results for rat liver grafts co-populated with parenchymal and biliary epithelial cells.

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Recent Advances in Decellularization and Recellularization for Tissue-Engineered Liver Grafts

Cells Tissues Organs ◽

10.1159/000452761 ◽

2016 ◽

Vol 203 (4) ◽

pp. 203-214 ◽

Cited By ~ 11

Author(s):

Yujia Wang ◽

Clara T. Nicolas ◽

Harvey S. Chen ◽

Jeffery J. Ross ◽

Silvana B. De Lorenzo ◽

...

Keyword(s):

Extracellular Matrix ◽

Liver Disease ◽

Evaluation Criteria ◽

Liver Graft ◽

Current Review ◽

Severe Liver Disease ◽

Control Modification ◽

End Stage ◽

Decellularized Liver ◽

Made In

Liver transplantation from deceased or living human donors remains the only proven option for patients with end-stage liver disease. However, the shortage of donor organs is a significant clinical concern that has led to the pursuit of tissue-engineered liver grafts generated from decellularized liver extracellular matrix and functional cells. Investigative efforts on optimizing both liver decellularization and recellularization protocols have been made in recent decades. In the current review, we briefly summarize these advances, including the generation of high-quality liver extracellular matrix scaffolds, evaluation criteria for quality control, modification of matrix for enhanced properties, and reseeding strategies. These efforts to optimize the methods of decellularization and recellularization lay the groundwork towards generating a transplantable, human-sized liver graft for the treatment of patients with severe liver disease.

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Recent Advances in Decellularization and Recellularization for Tissue-Engineered Liver Grafts

Cells Tissues Organs ◽

10.1159/000479597 ◽

2017 ◽

Vol 204 (3-4) ◽

pp. 125-136 ◽

Cited By ~ 14

Author(s):

Yujia Wang ◽

Clara T. Nicolas ◽

Harvey S. Chen ◽

Jeffery J. Ross ◽

Silvana B. De Lorenzo ◽

...

Keyword(s):

Extracellular Matrix ◽

Liver Disease ◽

Evaluation Criteria ◽

Liver Graft ◽

Current Review ◽

Severe Liver Disease ◽

Control Modification ◽

End Stage ◽

Decellularized Liver ◽

Made In

Liver transplantation from deceased or living human donors remains the only proven option for patients with end-stage liver disease. However, the shortage of donor organs is a significant clinical concern that has led to the pursuit of tissue-engineered liver grafts generated from decellularized liver extracellular matrix and functional cells. Investigative efforts on optimizing both liver decellularization and recellularization protocols have been made in recent decades. In the current review, we briefly summarize these advances, including the generation of high-quality liver extracellular matrix scaffolds, evaluation criteria for quality control, modification of matrix for enhanced properties, and reseeding strategies. These efforts to optimize the methods of decellularization and recellularization lay the groundwork towards generating a transplantable, human-sized liver graft for the treatment of patients with severe liver disease.

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Cardiac myocytes cultured on a basement membrane extract of the ehs tumor

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100142979 ◽

1986 ◽

Vol 44 ◽

pp. 270-271

Author(s):

L. Terracio ◽

A. Dewey ◽

K. Rubin ◽

T.K. Borg

Keyword(s):

Extracellular Matrix ◽

Basement Membrane ◽

Cardiac Myocytes ◽

Normal Tissue ◽

Cell Spreading ◽

Collagen Iv ◽

Basement Membrane Extract ◽

Membrane Extract ◽

Growth Development ◽

Multicellular Organisms

The recognition and interaction of cells with the extracellular matrix (ECM) effects the normal physiology as well as the pathology of all multicellular organisms. These interactions have been shown to influence the growth, development, and maintenance of normal tissue function. In previous studies, we have shown that neonatal cardiac myocytes specifically interacts with a variety of ECM components including fibronectin, laminin, and collagens I, III and IV. Culturing neonatal myocytes on laminin and collagen IV induces an increased rate of both cell spreading and sarcomerogenesis.

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Neutrophil migration through in vitro interstitial matrix

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100124872 ◽

1992 ◽

Vol 50 (1) ◽

pp. 894-895

Author(s):

J. Roemer ◽

S.R. Simon

Keyword(s):

Extracellular Matrix ◽

Smooth Muscle ◽

Cell Migration ◽

Smooth Muscle Cells ◽

Inflammatory Cell ◽

Neutrophil Migration ◽

Culture Conditions ◽

Aortic Smooth Muscle ◽

Specific Culture

We are developing an in vitro interstitial extracellular matrix (ECM) system for study of inflammatory cell migration. Falcon brand Cyclopore membrane inserts of various pore sizes are used as a support substrate for production of ECM by R22 rat aortic smooth muscle cells. Under specific culture conditions these cells produce a highly insoluble matrix consisting of typical interstitial ECM components, i.e.: types I and III collagen, elastin, proteoglycans and fibronectin.

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The extracellular matrix of echinoderm and amphibian eggs: Visualization in quick-frozen, deep-etched, and rotary-shadowed specimens

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010015784x ◽

1990 ◽

Vol 48 (3) ◽

pp. 60-61

Author(s):

Barry Bonnell ◽

Carolyn Larabell ◽

Douglas Chandler

Keyword(s):

Extracellular Matrix ◽

Plasma Membrane ◽

Sea Urchin ◽

Crystalline Structure ◽

Cortical Granule ◽

Two Dimensional ◽

Small Peptides ◽

Deep Etching ◽

Quick Freezing ◽

Acrosomal Reaction

Eggs of many species including those of echinoderms, amphibians and mammals exhibit an extensive extracellular matrix (ECM) that is important both in the reception of sperm and in providing a block to polyspermy after fertilization.In sea urchin eggs there are two distinctive coats, the vitelline layer which contains glycoprotein sperm receptors and the jelly layer that contains fucose sulfate glycoconjugates which trigger the acrosomal reaction and small peptides which act as chemoattractants for sperm. The vitelline layer (VL), as visualized by quick-freezing, deep-etching, and rotary-shadowing (QFDE-RS), is a fishnet-like structure, anchored to the plasma membrane by short posts. Orbiting above the VL are horizontal filaments which are thought to anchor the thicker jelly layer to the egg. Upon fertilization, the VL elevates and is transformed by cortical granule secretions into the fertilization envelope (FE). The rounded casts of microvilli in the VL are transformed into angular peaks and the envelope becomes coated inside and out with sheets of paracrystalline protein having a quasi-two dimensional crystalline structure.

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Extracellular matrix: the gatekeeper of tumor angiogenesis

Biochemical Society Transactions ◽

10.1042/bst20190653 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1543-1555 ◽

Cited By ~ 10

Author(s):

Maurizio Mongiat ◽

Simone Buraschi ◽

Eva Andreuzzi ◽

Thomas Neill ◽

Renato V. Iozzo

Keyword(s):

Extracellular Matrix ◽

Tumor Angiogenesis ◽

Signaling Cascades ◽

Cancer Growth ◽

Cell Behavior ◽

Metastatic Progression ◽

Surface Receptors ◽

The Matrix ◽

Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

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