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TRANSCRIPT
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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
https://xylyxbio.com/products/cell-culture/
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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
https://xylyxbio.com/products/cell-culture/http://xylyxbio.com/
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Rel
ativ
e ex
pre
ssio
n
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/
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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
pre
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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