Digitalization, technology andwellbeing -

Challenges and opportunitiesemerging trough

in-vitro and in-silico tissueengineeringProf. Jari Hyttinen,

Computational Biophysics and ImagingGroup (CBIG)

Tampere University of TechnologyELT and BioMediTech

TUT: A fully implantable ECG prototype

Evidence based medicine??

Change in Service?• From samples to flow of data!• Evidence based medicine – how toapprove the radically new concept?• New healthcare service models?Willem Einthoven 1909, ECG; ”Heart film”

TUT, BME 256 channel ECG, 2001

Wearble measurement system with ambientdata analysis: TUT/BME, Berkeley,

Ville-Pekka Seppä, Jari Viik, Jari Hyttinen

5Jari Hyttinen

Fibrobalasts from skinTarget cells

Applications of induced pluripotentstem cells (prof Yamanaka:

In vitro human cell models•iPSC provide patient specific human cells

=> In vitro drug discovery/toxicology•Disease models

=> In vitro drug discovery for risk groups•Personalized medicine

=>Cell based diagmosis=> Patient specific drug screening

hIPS derived cardiomyocytes preservepatient’s Long QT- phenotype

4/24/2016Jari Hyttinen

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Lahti, , Yamanaka, et al., Disease, Models & Mechanisms, 2011

Healthy control

Long-QT 1 and 2 patients

Fibrobalastsfrom skin

Cardiomyocytes

Control

LQT1

LQT2

1. Personal and clinical data profiling=> Diagnostics, follow up….

2. Gene profiling, proteomics,-omicsÞ Possible disease/drug responses

3. Computational models ofphysiology/biology

Þ Parsing and integration of the dataÞ Personalized treatment and diagnosis

4. hIPSC based in-vitro personalized cellmodels

=> Phenotypical diagnostics, and drugtesting

FuturePersonalized

Medicine

=> Precision medicine

Computational Biophysics and Imaging Group (CBIG):Prof Jari Hyttinen, 2 Senior Scientist, 3 post docs, 14 PhD students

We aim to develop novel methods to assess thebiological systems: 3D bioimaging, bioelectronics andelectrophysiology, “in vitro” and “in-silica” personalizedmedicine

• UnderstandingTE/biological system

• Implantable spare parts• Personalized medicine

Assessing cell responsesIn-vitro, in-vivo, ex-vico

Environment: Cells withengineered environment,biomaterials, stimuli, drugs

Computational modeling, “insilico” Concepts, hypothesis

- Bioelectricmeeasurements

- Electrophysilogy- 3D-bioimaging

- FEM, comparmental, CA,- Electrophysilogy, diffusion,

mechanic,…www.tut.fi/cbig

Cochlear inner structure

Individual stem cells on PLA

Rat eye @3µm

Composite biomaterialand stem cells in bone

Freeze dried collagn

no medication

,

0.02 µg Isoprenaline,

0.02 µg Isoprenaline and 20 µg Esmolol,.

0.02 µg Isoprenaline and 40 µg Esmolol,

Pekkanen-Mattila et al. 2009

In collaboration with Prof. Aalto-Setälä

Ahola et al. 2014

”Imaging” bioelectric activity:Cellular electrophysiology with MEA

- Label free- Non-invasive- Continuous

Heikkilä et al. Experimental Neurology, 2009Functionality of hESC neuronal network in vitro

collaboration, prof Aalto-Setälä, Prof Severi (University ogBologna), Prof Rodriguez (University of Oxford)

24.4.2016Jari Hyttinen

14

Paci et al. Ann. Biomed. Eng. 2013, CinC 2013 and 2014, BJP 2015

A) hiPSC-CM and B) O’Hara-Rudy adult CM “insilico” models.

A BhiPSC-CM Adult

LQT1 - IKs

A) control and LQT3 APs; B) effect of mexiletine onLQT3 APs;.

LQT3 INaL

iPS derived CM offers good model for drug screening:• the responses in iPS and adult CM are overall similar• but a higher sensitivity is observed in hiPSC-CM to current blokers.

=> Support synergistic approaches of pharmacological assessmentcombined in silico and in vitro hiPSC-CM technologies for safetyassessment and target identification during drug development.

Collaboration: prof Aalto-Setälä, Prof Severi (U. Bologna) and profRodriguez (U. Oxford)

Implantable cellsIn vitro cell and disease models

Human Spare Parts -program

HEART:Cardiomyocytes

NEURONALcells:

Neurons , glia

RETINA:RPE, BRB

BONE: Bonetissue for

implants andgrafts

biomaterials, microfluidic, biosensing, bioimaging, in-silicomodelling

Developing stem cell based solutions to medicine

Technologies for spare parts:

• Biomimetic environment with integratedtechnology for cell/tissue culturing andmechanical, electrical and chemicalstimulation

• Sensor and measurement solutions foranalysis and validation

• Modelling of cell functions, images andsignals for evaluation and validation oftissue engineered products

• Biomaterials for tissue engineering:- Hydrogels for soft tissue applications- Biodegradable personalized 2D and 3D

textile structures- Biodegradable sensors

Human Spare Parts - Technology

1. Personal and clinical data profiling=> Diagnostics, follow up….

2. Gene profiling, proteomicsÞ Possible disease/drug responses

3. Computational models ofphysiology/biology

Þ Parsing and integration of the dataÞ Personalized treatment and diagnosis

4. hIPSC based in-vitro personalized cellmodels

=> Phenotypical diagnostics, and drugtesting

FuturePersonalized

Medicine

=> Precision medicine

• We need:• Practical health related problems and NEEDS• ”Bio” measurement and imaging challanges• Espeacially: problems spanning from cells to

patient: Cardiac, Neuronal. Epithelia…

• What we offer:• Expertise on biomeasurements and imaging

(from cell to bedside)• Expertise on physiological and biological signals• Expertise on ”in-silico” medicine: From physics

to tissues and measurements

http://www.stanford.edu/class/history13/earlysciencelab/body/brainpages/brain.html

New science New personalizedmedicine and safety

PersonalizedSpareparts

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Jari Hyttinen 24.4.2016

• Call for sessions and tracks: 20th October 2016• Call for EMBEC price nominations: 31st Jan 2017• DL for papers/abstracts: 28th Feb 2017• http://embec2017.org/ www.nbc2017.org

22

Stefan W. HellNobel Laureate, ProfessorDirector, Max Planck Institute for

Biophysical ChemistryDept. of NanoBiophotonicsUniversity of GöttingenGermany

Gordon G. WallaceProfessorAustralian Research Council LaureateFellowUniversity of Wollongong, AustraliaDirector of the Australian NationalFabrication Facility, Materials Node

Risto IlmoniemiAcademy ProfessorDepartment of Neuroscience andBiomedical EngineeringAalto University, Helsinki, Finland

Professor Molly Stevens FREngFaculty of Engineering, Department ofMaterialsProf of Biomedical Materials&RegenerativeMedicineImperial Collage, London, UK

Manuel BardièINSERM (National Institute of Health and MedicalResearch)Toulouse, France

Anthony P. F. Turner PhD, DSc.Head of the Biosensors & Bioelectronics CentreLinköping UniversitySweden.

Jukka-Pekka OnnelaDepartment of BiostatisticsHarvard T.H. Chan School of Public HealthBoston, MA 02115, USA

Digital phenotyping

AcknowledgementHyttinen laboratory,CBIGUnderstanding hIPSCCardiomyocytesPhD Michelangelo PaciMSc Antti AholaBSc Ville MuhonenBSc Ahsan Abbas

Modelling and analysis ofneuronal and astrocytefunctionsMSc (PhD) Kerstin LenkMSc Inkeri VornanenMSc Narayan SubramaniyamMSc Emre Kapucu

ElectroMechanobiologyMSc Heidi HalonenMSc Leena Jaatinen (at ETHZ)

24.4.2016

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Financing:EU 7th Framework, FET-OPENAcademy of FinlandTekes, FinlandFinnish Cultural Foundation, Pirkanmaa CulturalFoundation, Ehrnroth Foundation, Wihuri Fundation..…

BioMediTech Tampere,Human Spare Part TeamTUT: Prof Minna Kellomäki

Prof Jukka LekkalaProf Pasi Kalllio

UTA: PhD Heli SkotmanPhD Susanna NarkilahtiPhD Susanna MiettinenProf Katriina Aalto-Setälä

TUT: Prof Jari Viik, Hannu EskolaTUH; Cardiology, Neurosurgery, RadiologyHelsinki University prof. Samuli SiltanenETHZ: Profs Janos Vörös and Marcy WongUniversity of Bologna: Prof. Stefano SeveriINRIA France: Dr Hugues Berry iTohoku University: Prof Tetsuo TanakaTU Ilmenau: prof:s Peter Peter Husar and AndreasSchoberFranhofer Institute: Dr. Franz KlefenzUniversity of Ghent: prof Jan van FleterenOxfort Univeristy: Prof Blanca Rodriquez

Cellular Biophysics of the EyePhD Soile NymarkMSc Julia JohanssonMSc Iina VainioMSc Amna Abu KhamidaikhMSc Aapo TervonenMSc Virpi Savolainen

X-ray MicrotomographyPhD Antti AulaMsc Markus HannulaMSc Nathaniel NarraMSc Ilmari TamminenMSC Kalle Lehto

3D Optical ImagingMSc Mari Plojärvi-LehtiMSc Olli KoskelaMSc Birhanu BelayBSc Toni Montonen

www.tut.fi/cbig www.biomeditech.fi