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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
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
7
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
• 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
24
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