Scaffold System for Tissue Regeneration (Engineering)€¦ · iHuman •Obama Announces Key Actions to Reduce Organ Waiting List •Centennial Challenges: Vascular Tissue Challenge

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

http://www.sciencedirect.com/science?_ob=IssueURL&_tockey=

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


iHuman


eGFP H1-Ecs

DsRed H1-vSMCs

iHuman

vessel

maturation


iHuman


iHuman vessel, lumen & maturation


iHuman



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’


iHuman


In-vitro assessment of

permeability

eGFP H1-Ecs

Dextran-Texas Red


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


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


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

• 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

• 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

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

• Obama Announces Key Actions to Reduce Organ Waiting List

• Centennial Challenges: Vascular Tissue Challenge

• Grow Human Tissue to Aid in Deep Space Exploration


White House. NASA, New Organ, Jun 2016

iHuman

https://www.whitehouse.gov/the-press-office/2016/06/13/fact-sheet-obama-administration-announces-key-actions-reduce-organ

http://www.nasa.gov/directorates/spacetech/centennial_challenges/vascular_tissue.html

https://neworgan.org/whats-new.php

iHuman for Dentistry, Medicine and Health

Off The Human, For The HumaniHuman

Documents

Scaffold System for Tissue Regeneration (Engineering)€¦ · iHuman •Obama Announces Key Actions to Reduce Organ Waiting List •Centennial Challenges: Vascular Tissue Challenge