scaffold system for tissue regeneration (engineering)€¦ · ihuman •obama announces key actions...

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