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Transcript of Human fibrotic lung ECM substrates=ZeVi^X hiZaaViZ XZaah V ^ciZ\gViZ ^cid (9 I^hhjZHeZX A^kZg :8B...

  • Interstitial lung disease, including idiopathic pulmonary fibrosis

    (IPF), remains high-risk for drug development, as in-vitro

    techniques fail to recapitulate the human in-vivo disease

    environment. Xylyx Bio offers custom fibrotic human lung ECM

    substrates to significantly improve in-vitro disease modeling and

    drug development in a disease-relevant setting. 

    Features

    Recapitulate human lung fibrosis in vitro

    Disease-specific ECM composition

    Applicable in 2D and 3D in-vitro models 

    Compatible with high-throughput screening 

    Xeno-free

    IPF tissue

    TissueSpec®

    IPF Scaffold

    αSM

    A

    TissueSpec® IPF Scaffolds support fibrotic disease-associated phenotype of primary human pulmonary fibroblasts significantly more

    consistent with human IPF tissue than cells cultured on plastic. (a) Immunostaining of alpha smooth actin (αSMA). (b) Quantification ofsecreted basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGFβ). Scale bar: 50 µm. * p < 0.05.

    IPF-associated phenotype of pulmonary fibroblasts

    Human fibrotic lung ECM substrates

    The cell environment company xylyxbio.com

    Accelerating anti-fibrotic drug development

    TissueSpec® ECM Scaffold

    TissueSpec® ECM Hydrogel

    NativeCoat™ ECM Coating

    Organotypic ECM platform for anti-fibrotic drug development

    abFGF (secreted)

    b

    plasticTissueSpec®

    IPF Scaffold

    TGFβ (secreted)

    __plasticTissueSpec®

    IPF Scaffold

    *

    cell-based assays

    Lung ECM

    Lung ECM products

    24

    18

    12

    6

    100

    90

    80

    70

    pg/m

    L

    pg/m

    L

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  • a b

    The cell environment company xylyxbio.com

    Partner with Xylyx Bio!

    We are actively partnering with leading pharmaceutical companies to further develop and integrate our disease-specific ECM

    products into cell-based assays and established workflows to accelerate pharmaceutical drug discovery and development.

    For partnering opportunities, contact us today at [email protected]

    Disease-relevant ECM platform for predictive anti-fibrotic drug testing

    TissueSpec® IPF Scaffolds are a physiologic human ECM environment for predictive drug testing. (a) Growth curves and (b) relative

    expression of COL1A1 by human pulmonary fibroblasts after treatment with an anti-fibrotic drug candidate (PF 3644022).

    b

    TissueSpec® IPF Scaffolds have a composition and mechanical stiffness consistent with human IPF tissue. (a) Quantification of key ECM

    components shows high similarity between TissueSpec® IPF Scaffolds and human IPF tissue. (b) Mechanical stiffness of TissueSpec®

    IPF Scaffolds matches IPF tissue. * p < 0.001.

    Drug testing

    kP

    a

    IPF

    tissue

    TissueSpec®

    IPF  Scaffold

    plastic

    Chan

    ge

    in c

    ell num

    ber

    from

    bas

    elin

    e (%

    )

    TissueSpec® IPF Scaffolds recapitulate the IPF disease environment

    ECM components

    collagens elastin

    a

    Mechanical stiffness

    GAG

    TissueSpec® IPF Scaffold

    IPF tissue*

    Time (day)

    control

    drug (PF 3644022)

    TissueSpec® IPF Scaffold

    plastic

    Rel

    ativ

    e ex

    pre

    ssio

    n

    control drug

    COL1A1

    µg/m

    g

    1000

    100

    10

    1

    1.0

    0.5

    0.0

    150

    125

    100

    0 2 4 6

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  • Rel

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    ssio

    Xylyx Bio's custom human (normal or fibrotic) liver ECM

    substrates recreate the fibrotic liver environment in vitro to

    offer a significantly improved disease-relevant setting for

    fibrosis modeling and drug development.

    Features

    Recapitulate human liver fibrosis in vitro

    Fibrotic liver ECM composition

    Applicable in 2D and 3D in-vitro models 

    Compatible with high-throughput screening 

    Xeno-free

    Platform for modeling fibrotic liver disease

    Human fibrotic liver ECM substrates

    IN MATRICO® Drug Discovery xylyxbio.com

    Accelerating anti-fibrotic drug development

    TissueSpec® ECM Scaffold

    TissueSpec® ECM Hydrogel

    NativeCoat™ ECM Coating

    Organotypic ECM platform for anti-fibrotic drug development

    cell-based assays

    Liver ECM

    Normal and Fibrotic Liver ECM substrates

    cGene expressionb

    1

    Cell proliferation

    Cel

    l num

    ber

    (10

    E4)

    100

    75

    25

    1.0

    0.5

    0.0

    50

    03 5 7

    collagen I coat

    Normal Liver ECM Scaffold

    Fibrotic Liver ECM Scaffold

    ACTA2 COL1A1

    Hepatic stellate cells (a) integrate into 3D TissueSpec® Liver ECM Scaffolds and (b) exhibit differential expression of fibrosis-

    related genes in liver ECM scaffolds compared to plastic. (c) Cells proliferate over 7 days in normal and fibrotic liver ECM

    scaffolds with higher proliferation in fibrotic liver ECM scaffolds, consistent with progressive fibrotic liver disease.

    Cell morphologya

    pla

    stic

    Norm

    al L

    iver

    EC

    M S

    caff

    old

    _H&E stain trichrome stain

    col I coat no ECM

    2.0

    Time (days)LOXL2

    1.5

    Normal

    Fibrotic

    Plastic

    Normal + TGFβFibrotic + TGFβPlastic + TGFβ

    https://xylyxbio.com/products/cell-culture/

  • TGFβ (25nM)TGFβ-

    We actively partner with leading pharmaceutical companies to integrate products in drug discovery and screening workflows

    and develop specialized disease-specific cell-based assays.

    For partnering opportunities and any other inquiries contact us today at [email protected]

    Primary hepatic stellate cells (a) in normal and fibrotic human liver ECM hydrogels. (b) Differential secretion of connective

    tissue growth factor (CTGF) in human liver ECM scaffolds after 72 hours. (c) Hepatic stellate cells have more physiologic

    gene expression in liver ECM hydrogels compared to other substrates. (d) After treatment with Erlotinib for 72 hours, hepatic

    stellate cells in liver ECM hydrogels show greater sensitivity at higher drug concentrations.

    Anti-fibrotic compound testing

    Characterization of hepatic stellate cells IN MATRICO®

    IN MATRICO® Drug Discovery xylyxbio.com

    Partner with us!

    Primary human hepatic stellate cells

    were cultured with or without TGFβ(25nM). Cells show continual

    proliferation on plastic but attenuated

    proliferation in liver ECM hydrogels

    in response to Pirfenidone (2.7mM),

    consistent with expected antifibrotic

    effect of Pirfenidone.

    bCell morphologya CTGF secretion

    dGene expressionc Drug response

    Cel

    l num

    ber

    (x1

    00

    0)

    Rel

    ativ

    e ex

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    ssio

    n

    Cel

    l vi

    abili

    ty (

    %)

    CTG

    F

    (pg/m

    L/1

    00

    0 c

    ells

    )

    120

    90

    60

    30

    0.1 101 100Erlotinib (µM)

    250

    150

    50

    Normal ECM Fibrotic ECM Plastic

    3

    2

    1

    0ACTA2 COL1A1 LOXL2 MMP2

    60

    40

    20

    0

    60

    40

    20

    0

    60

    40

    20

    00 1 2 3 0 1 2 3 0 1 2 3

    Time (day)Time (day)Time (day)

    Plastic (no ECM) Normal ECM Fibrotic ECM

    +Normal ECM Fibrotic ECM

    Normal 

    Fibrotic 

    Plastic 

    +- +- +-

    350

    Vehicle (DMSO) TGFβ Pirfenidone TGFβ + Pirfenidone

    Normal

    Fibrotic

    Plastic

    Normal + TGFβFibrotic + TGFβPlastic + TGFβ

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