millennium talks 18.5.2017 katriina aalto-setälä
TRANSCRIPT
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Human Spare Parts
Katriina Aalto-SetäläProfessor, cardiologistUniversity of Tampere
Heart Center, Tampere University Hospital18.5.2017
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Stem cells
Based on differentiationcapacity
Totipotent
Tissue specific
Multipotent
pluripotent
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Stem cells
Pluripotent stem cells
Multipotent stemcells
All tissues
Erythrocytes
PlateletsLeucocytes
Pancretic cells
Hepatic cells
Neurons
Cardiac cells
Hematopoeticstem cells
Tissue specific stem cells Adult stemcells
Mesenchymalstem cells
ESC, iPSC
BoneCartilageFat
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Clinical trials with adult stem cells(5915 trials)
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Clinical trials with mesenchymalstem cells (719 trials)
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Clinical trials with pluripotent stem cells(57 trials)
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Hematopoetic stem cells
First bone marrow derivedstem cell treatment in 1968in Finland.
Allogenic stem cell treatmentsFinland
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Limbal stem cellsLimbal stem cells reside in the depth of the crypts
http://www.stembook.org/node/588
LSCD
limbal stem cell deficiency
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First stem cell based product in Europe
February 20, 2015 – The European Commission has granted a conditional marketing authorization, under Regulation (EC) No 726/2004, to Holoclar®
Ex vivo expanded autologous human corneal epithelial cells containing stem cells for unilateral ocular burns
CHIESI Farmaceutici S.p.A
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Mesenchymal stem cells� Adult stem cells, multipotent
� Found in bone marrow, fat etc
� Produce e.g. bone, cartilage, fat
� Immunosupressive� Graft-versus-host
� Cell therapy: � Bone� Cartilage� Brain diseases� Heart failure
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Differentiation of mesenchymalstem cells
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Mesenchymal stem cells in stroke
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Mesenchymal stem cells in heart failure
?
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Pluripotent stem cellsEmbryonic stem cell vs iPS cells
Blastocyct
Differentiated cellPatient samplee.g. skin, blood
Inner cell mass
Pluripotentstem cell
iPS cell
Embryonic stemcell
Differentiate into any cell
Genotype and disease-spesific cells!
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Pluripotent stem celltherapies
� Spinal cord injury� Geron
� hESC-derived neurons� Started 2010� Ended 2011 (due to financial reasons)
� Eye disease/retinal degeneration� Advanced Cell Technolohgies
� hESC started 2011 � No safety issues
� Riken� iPSC, injected 2014 � 2017: no improvement in vision� New enrollments
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Stem cell treatment of diabetes
� Type I diabetes� Insulin not produced byb-cells
� Cell therapy available: donor-derivedpancreatic cells
� hESC/iPSC derived b-cells
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Stem cell for cardiac repair
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Cardiac progenitor cells
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Direct reprogramming of cardiomyocytes
From
plu
ripot
ent
stem
cells
Dir
ect
re-
pro
gram
min
g
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Disease modellingiPSC-derived cardiomyocytes
Patient- and mutation specific cardiomyocytes
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Contraction
Electrophysiology
Calcium transients
Normal LQTS
Analysis of cardiomyocytes
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Cardiac adverse effects (”ECG” of a cell)
Baseline
Drug-X 3 µM
Drug-X 15 µM
Pharmaceutical industry
Kuusela J et al, 2016
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Personilized medication
� Same disease
� Same gene
� Different mutation
� Different drug response
� iPSC-derived cell reproduce thedrug response
Arrhythmiasabolished
No effect
Patient
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Cardiomyocytes
Penttinen et al 2015
Familial arrhythymia (CPVT)• RyR2 gene mutations
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Traditional vs stem cell-baseddrug discovery
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New medication
Cell therapy
Personilizedmedication
Stem cells in medicine
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Gene surgery
Disease-modelling
Cell tranplants
New drugs
Gene modification
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Thank you!