The presentation of Katriina Aalto-Setälä at the Millennium Talks Workshop 18.5.2017: "Human Spare Parts"

1. Human Spare Parts
Katriina Aalto-Setälä
Professor, cardiologist
University of Tampere
Heart Center, Tampere University Hospital
18.5.2017

2. Stem cells
Based on
differentiation
capacity
Totipotent
Tissue specific
Multipotent
pluripotent

3. Stem cells
Pluripotent stem cells
Multipotent stem
cells
All tissues
Erythrocytes
Platelets
Leucocytes
Pancretic cells
Hepatic cells
Neurons
Cardiac cells
Hematopoetic
stem cells
Tissue specific stem cells Adult stem
cells
Mesenchymal
stem cells
ESC, iPSC
Bone
Cartilage
Fat

4. Clinical trials with adult stem cells
(5915 trials)

5. Clinical trials with mesenchymal
stem cells (719 trials)

6. Clinical trials with pluripotent stem cells
(57 trials)

7. Hematopoetic stem cells
First bone marrow derived
stem cell treatment in
1968
in Finland.
Allogenic stem cell treatments
Finland

8. Limbal stem cells
Limbal stem cells reside in the depth of the crypts
http://www.stembook.org/node/588
LSCD
limbal stem cell deficiency

9. 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

10. 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

11. Differentiation of mesenchymal
stem cells

12. Mesenchymal stem cells in stroke

13. Mesenchymal stem cells in
heart failure
?

14. Pluripotent stem cells
Embryonic stem cell vs iPS cells
Blastocyct
Differentiated cell
Patient sample
e.g. skin, blood
Inner cell mass
Pluripotent
stem cell
iPS cell
Embryonic stem
cell
Differentiate into any cell
Genotype and disease-spesific cells!

15. Pluripotent stem cell
therapies
— 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

16. Stem cell treatment of diabetes
— Type I diabetes
— Insulin not produced by
b-cells
— Cell therapy available:
donor-derived
pancreatic cells
— hESC/iPSC derived b-
cells

17. Stem cell for cardiac repair

18. Cardiac progenitor cells

19. Direct reprogramming of
cardiomyocytes
From
pluripotentstem
cells
Directre-
programmin
g

20. Disease modelling
iPSC-derived cardiomyocytes
Patient- and mutation specific cardiomyocytes

21. Contraction
Electrophysiology
Calcium transients
Normal LQTS
Analysis of cardiomyocytes

22. Cardiac adverse effects (”ECG” of a cell)
Baseline
Drug-X 3 µM
Drug-X 15 µM
Pharmaceutical industry
Kuusela J et al, 2016

23. Personilized medication
— Same disease
— Same gene
— Different mutation
— Different drug response
— iPSC-derived cell reproduce the
drug response
Arrhythmias
abolished
No effect
Patient
1
2
3
4
5
6
1
2
3
4
5
6
Cardiomyocytes
Penttinen et al 2015
Familial arrhythymia (CPVT)
• RyR2 gene mutations

24. Traditional vs stem cell-based
drug discovery

25. New medication
Cell therapy
Personilized
medication
Stem cells in medicine

26. Gene surgery
Disease-
modelling
Cell tranplants
New drugs
Gene modification

27. Thank you!