Scaffold System for Tissue Regeneration (Engineering)€¦ · iHuman •Obama Announces Key Actions...
Transcript of Scaffold System for Tissue Regeneration (Engineering)€¦ · iHuman •Obama Announces Key Actions...
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Vascularized, innervated, standard and live ‘In- vitro Human’
iHuman Program
National University Health System
National University of Singapore
iHuman
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iHuman –
hESC derived ‘Lab-Human’ platformiHuman
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iHuman – Functional tissue-organ from hESC
Ectoderm
Mesoderm
Keratinocytes
Neurons
Serous cells
Osteogenic cells
Chondrogenic cells
MSCs, Fibroblasts,
Adipocyte
Endotheliocyte
Smooth, Cardio,
Skeletal Myocytes
Hepatocytes
Kidney cells
Human
pluripotent
stem
cells
Skin/Mucosa
Nerve
Bone
Cartilage
Connective
Tissues
Blood vessels
Cardio, Smooth,
Skeletal Muscles
Liver tissue
Kidney tissueEndoderm
Functional,
Vascularized
& Innervated
Tissue-Organ
Single tissue Multi lineage tissues
iHuman
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iHuman –
Vascularized skin/mucosa platformiHuman
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Dermal
epidermal
co-culture
UK International Patent PCT/SG2015/05030, Published 17 Mar 2016 WO 2016/039687A1
9 wks, bar: 100 µm iHuman
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Full-thickness hESC skin/mucosa
9 wks, bar: 100 µm
UK International Patent PCT/SG2015/05030, Published 17 Mar 2016 WO 2016/039687A1
iHuman
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hESC vessels by Ec-SMC co-culture
H1-Ecs
(Calcein AM)
H1-vSMCs
(DsRed)H1-Ecs + H1-vSMCs
(MERGE)
Stem Cell Res Ther, Nov 2015
iHuman
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hESC vessels by Ec-SMC co-culture
eGFP H1-Ecs DsRed H1-vSMCs
Stem Cell Res Ther, Nov 2015
iHuman
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iHuman vessels
by Ec-SMC co-
culture
eGFP H1-Ecs
DsRed H1-vSMCs
UK International Patent PCT/SG2016/050282
iHuman
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eGFP H1-Ecs
DsRed H1-vSMCs
iHuman vessel
maturation
UK International Patent PCT/SG2016/050282
iHuman
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eGFP H1-Ecs
DsRed H1-vSMCs
iHuman
vessel
maturation
UK International Patent PCT/SG2016/050282
iHuman
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iHuman vessel, lumen & maturation
UK International Patent PCT/SG2016/050282
iHuman
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UK International Patent PCT/SG2016/050282
iHuman vessel, lumen & maturation
iHuman
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In-vitro assessment of permeability
Mature Microvasculature
Nuclei (Endothelial/ Smooth Muscle cells) Endothelial tubes
Fluorescent conjugated- Permeant (ex. Dextran-Texas Red)
Mature microvasculature + Histamine 5’
UK International Patent PCT/SG2016/050282
iHuman
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In-vitro assessment of
permeability
eGFP H1-Ecs
Dextran-Texas Red
UK International Patent PCT/SG2016/050282
iHuman
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Integration of hESC vessel with skin/mucosa
+
UK International Patent PCT/SG2016/050282, PCT/SG2015/05030, WO 2016/039687A1
iHuman
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Vascularized hESC skin/mucosa
UK International Patent PCT/SG2016/050282, PCT/SG2015/05030, WO 2016/039687A1
iHuman
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iHuman –
CNS and PNS neural platformiHuman
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Neural differentiation
Nestin
Tuj1
DA
PI
J Biomed Sci, Feb 2016
iHuman
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hESC dopaminergic neurons
O4 Tuj1 Dapi
J Biomed Sci, Feb 2016
iHuman
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Neural crest peripheral neurons
Peripherin β-tubulinIIIJ Dent Res, 2015
iHuman
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Integration of hESC nerve with organoid
Unpublished
+iHuman
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iHuman –
Vascularized and innervated organ platformiHuman
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Integration of iHuman organoid with vessel & nerve
UK International Patent PCT/SG2016/050282, PCT/SG2015/05030, WO 2016/039687A1
iHuman
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Additive manufacture of iHuman vascularized, innervated organ
Unpublished
iHuman
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• Assessment of human relevant function and toxicity/safety for
therapies, drugs, food, chemicals, materials and techniques;
• Study of ageing, pathogen, disease and prevention
− 86 WoS - Scopus publications on iHuman
− 27 WoS - Scopus publications on iHman applications
− 2 UK-International patents
− 1 Spinoff
iHuman platform for clinic and health
iHuman
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• Organotypic Skin Model (2014). UK Patent
• Vascularized Tissue, Skin or Mucosa Equivalent. UK Patent
• ZNF750 is a lineage-specific TUMOR suppressor in squamous cell CARCINOMA [CaSki]. Oncogene
• hESCs-derived keratinocytes as a novel epidermal cellular model in AGING studies. ScholarBank
• Differential effects of the extracellular microenvironment on hESCs differentiation into keratinocytes and their subsequent
replicative lifespan. Tissue Eng
• Telomere length is regulated by FGF-2 in hESCs and affects the life span of its differentiated progenies. Biogerontology
• Investigation of telomere and telomerase in hESCs and its progenies. ScholarBank
• Potential applications of keratinocytes derived from hESCs. Biotechnol J
• Innate IMMUNE response of hESC derived-fibroblasts and mesenchymal stem cells to periodontopathogens. Stem Cells Int
• hESCs derived keratinocyte as an in vitro research model for the study of immune response. J Oral Pathol Med
iHuman platform for clinic and health
iHuman
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• Development of hESC platforms for human HEALTH-SAFETY evaluation. J Peking Univ
• Pioneering report on hESC progenies for toxicity study and test. Cloning Stem Cells
• Evaluating biotoxicity with fibroblasts derived from hESCs. Toxicol In Vitro
• Development of hESC model for toxicity evaluation. J Peking Univ
• Pluripotent stem cells: an in vitro model for nanotoxicity assessments. J Appl Toxicol
• Pioneering report of dentistry research on hESCs for genotoxicity study and test. Stem Cells Dev
• Role of hESCs and Derived Progenies in Genotoxicity Testing. ScholarBank
• Evaluation of hESCs and their Differentiated Fibroblastic Progenies as Cellular Models for In Vitro Genotoxicity. J Biotechnol
• HESCs for genotoxicity testing. ScholarBank
• Differential resistance of hESCs and somatic cell types to oxidative stress and genotoxicity may be dependent on innate basal
intracellular ROS levels. Folia Histochem Cytobiol
• Assessment of mitomycin C-induced cytotoxicity and genotoxicity utilizing somatic progenies of hESCs. ScholarBank
• Cytotoxicity of two dental materials on fibroblasts derived from hESCs. J Peking Univ
• Cytotoxicity of Silver Nanoparticles in hESCs-Derived Fibroblasts and an L-929 Cell Line. J Nanomaterve areas.
iHuman platform for clinic and health
iHuman
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• Pioneering report on hESCs and progenies to oxidative stress. Photomed Laser Surg
• Hydrogen Peroxide-Induced Cytotoxicity and Oxidative DNA Damage on hESCs and their Differentiated
Fibroblast-like Progenies. ScholarBank
• Short periods of cyclic MECHANICAL strain enhance triple-supplement directed osteogenesis and bone nodule
formation by hESCs in vitro. Tissue Eng
• Investigation of hESCs-Derived Keratinocytes as an In Vitro Research Model for Mechanical Stress Dynamic
Response. Stem Cell Rev
• Fabrication and evaluation of electrohydrodynamic jet 3D PRINT-ed polycaprolactone / chitosan cell carriers
using hESC-derived fibroblasts. J Biomater Appl
• Comparison of Osteogenesis of hESCs within 2D and 3D culture systems. Scand J Clin Lab Invest
iHuman platform for clinic and health
iHuman
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Stem Cells Dev. 2008
H1
Extra-telomeric signals
Chromosomalbreak
IMR
-90
: h-lung fib
robla
st
0.06µg/ml MMCUntreated
Chromosomalbreak
Loss of telomeric end
PNA – FISH
iHuman
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Stem Cells Dev. 2008
H1
IMR
-90
: h
-lung fib
robla
st
0.06µg/ml MMCUntreated
M – FISH
iHuman
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Untreated 1G γ0.5G γ
H1
h-lym
phocy
te
Chromosomalbreak
Fragment
Chromosomalbreak
Fra
gm
ent
Chromosomalbreak
PNA – FISH
J Biotechnol, 2014
iHuman
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With vaccinia/cowpox virus
H9-pVero E6 (Monkey kidney keratinocyte)
Unin
fecte
d
Counte
r sta
ined
Infe
cte
d
Anti-v
accin
ia
Unpublished
iHuman
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With influenza A virus, subtype H1N1
H9-pMDCK (Dog kidney keratinocyte)
Unpublished
iHuman
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• Regenerative medicine
• Development and gene control of body cell,
tissue, organ, system of implant bed/host
• Assessment of human relevant function and
toxicity/safety for implant materials, devices and techniques
• Study of pathogen, disease and prevention for implant
iHuman for AM, Implantology, R&D
Tissue Eng 2003, Biomater 2004, 2005
iHuman
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Alvelac™
Co-developed by FOD, NUHS and BSI
Biomed Mater 2008, Scand J Clin Lab Invest 2008, J Biomater Appl 2008, Biomed Mater 2009
iHuman
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3D Printing Ti Implant
Co-developed by SIMTech and FOD, NUS Mater Des, 2010 Jun
iHuman
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ZOI
ZOI
Positive
controlScaffold
Scaffold area
Positive
control
Function & safety study
of material
iHuman
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Osteoblast attachment, migration & proliferation
*FDA stains the living cells into green. *PI stains the dead cells into red.
With gel, day 14 Without gel, day 14
Mater Des, 2010 Jun
iHuman
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With gel, day 21
Osteoblast viability and collagen-I deposition
Green: osteoblasts Red: collagen-I
Without gel, day 21
Mater Des, 2010 Jun
iHuman
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• Development and gene control of body cell, tissue, organ, system;
• Delivery of gene and protein for cell based therapy;
• Regenerative medicine;
• Assessment of human relevant function and toxicity/safety for therapies,
drugs, food, chemicals, materials and techniques;
• Human relevant environment analysis of water, soil, air, natural/artificial
and chemical/physical products and techniques;
• Study of pathogen, disease and prevention
iHuman platform for clinic and health
iHuman
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• Obama Announces Key Actions to Reduce Organ Waiting List
• Centennial Challenges: Vascular Tissue Challenge
• Grow Human Tissue to Aid in Deep Space Exploration
iHuman platform for clinic and health
White House. NASA, New Organ, Jun 2016
iHuman
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iHuman for Dentistry, Medicine and Health
Off The Human, For The HumaniHuman