Vascularized, innervated, standard and live ‘In- vitro Human’ iHuman Program National University Health System National University of Singapore iHuman
Vascularized, innervated, standard and live ‘In- vitro Human’
iHuman Program
National University Health System
National University of Singapore
iHuman
iHuman –
hESC derived ‘Lab-Human’ platformiHuman
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
iHuman –
Vascularized skin/mucosa platformiHuman
Dermal
epidermal
co-culture
UK International Patent PCT/SG2015/05030, Published 17 Mar 2016 WO 2016/039687A1
9 wks, bar: 100 µm iHuman
Full-thickness hESC skin/mucosa
9 wks, bar: 100 µm
UK International Patent PCT/SG2015/05030, Published 17 Mar 2016 WO 2016/039687A1
iHuman
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
hESC vessels by Ec-SMC co-culture
eGFP H1-Ecs DsRed H1-vSMCs
Stem Cell Res Ther, Nov 2015
iHuman
iHuman vessels
by Ec-SMC co-
culture
eGFP H1-Ecs
DsRed H1-vSMCs
UK International Patent PCT/SG2016/050282
iHuman
eGFP H1-Ecs
DsRed H1-vSMCs
iHuman vessel
maturation
UK International Patent PCT/SG2016/050282
iHuman
eGFP H1-Ecs
DsRed H1-vSMCs
iHuman
vessel
maturation
UK International Patent PCT/SG2016/050282
iHuman
iHuman vessel, lumen & maturation
UK International Patent PCT/SG2016/050282
iHuman
UK International Patent PCT/SG2016/050282
iHuman vessel, lumen & maturation
iHuman
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
In-vitro assessment of
permeability
eGFP H1-Ecs
Dextran-Texas Red
UK International Patent PCT/SG2016/050282
iHuman
Integration of hESC vessel with skin/mucosa
+
UK International Patent PCT/SG2016/050282, PCT/SG2015/05030, WO 2016/039687A1
iHuman
Vascularized hESC skin/mucosa
UK International Patent PCT/SG2016/050282, PCT/SG2015/05030, WO 2016/039687A1
iHuman
iHuman –
CNS and PNS neural platformiHuman
Neural differentiation
Nestin
Tuj1
DA
PI
J Biomed Sci, Feb 2016
iHuman
hESC dopaminergic neurons
O4 Tuj1 Dapi
J Biomed Sci, Feb 2016
iHuman
Neural crest peripheral neurons
Peripherin β-tubulinIIIJ Dent Res, 2015
iHuman
Integration of hESC nerve with organoid
Unpublished
+iHuman
iHuman –
Vascularized and innervated organ platformiHuman
Integration of iHuman organoid with vessel & nerve
UK International Patent PCT/SG2016/050282, PCT/SG2015/05030, WO 2016/039687A1
iHuman
Additive manufacture of iHuman vascularized, innervated organ
Unpublished
iHuman
• 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
• 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
• 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
• 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
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
Stem Cells Dev. 2008
H1
IMR
-90
: h
-lung fib
robla
st
0.06µg/ml MMCUntreated
M – FISH
iHuman
Untreated 1G γ0.5G γ
H1
h-lym
phocy
te
Chromosomalbreak
Fragment
Chromosomalbreak
Fra
gm
ent
Chromosomalbreak
PNA – FISH
J Biotechnol, 2014
iHuman
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
With influenza A virus, subtype H1N1
H9-pMDCK (Dog kidney keratinocyte)
Unpublished
iHuman
• 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
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
3D Printing Ti Implant
Co-developed by SIMTech and FOD, NUS Mater Des, 2010 Jun
iHuman
ZOI
ZOI
Positive
controlScaffold
Scaffold area
Positive
control
Function & safety study
of material
iHuman
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
With gel, day 21
Osteoblast viability and collagen-I deposition
Green: osteoblasts Red: collagen-I
Without gel, day 21
Mater Des, 2010 Jun
iHuman
• 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
• 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
iHuman for Dentistry, Medicine and Health
Off The Human, For The HumaniHuman