Human Spare Parts

Katriina Aalto-SetäläProfessor, cardiologistUniversity of Tampere

Heart Center, Tampere University Hospital18.5.2017

Stem cells

Based on differentiationcapacity

Totipotent

Tissue specific

Multipotent

pluripotent

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

Clinical trials with adult stem cells(5915 trials)

Clinical trials with mesenchymalstem cells (719 trials)

Clinical trials with pluripotent stem cells(57 trials)

Hematopoetic stem cells

First bone marrow derivedstem cell treatment in 1968in Finland.

Allogenic stem cell treatmentsFinland

Limbal stem cellsLimbal stem cells reside in the depth of the crypts

http://www.stembook.org/node/588

LSCD

limbal stem cell deficiency

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

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

Differentiation of mesenchymalstem cells

Mesenchymal stem cells in stroke

Mesenchymal stem cells in heart failure

?

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!

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

Stem cell treatment of diabetes

� Type I diabetes� Insulin not produced byb-cells

� Cell therapy available: donor-derivedpancreatic cells

� hESC/iPSC derived b-cells

Stem cell for cardiac repair

Cardiac progenitor cells

Direct reprogramming of cardiomyocytes

From

plu

ripot

ent

stem

cells

Dir

ect

re-

pro

gram

min

g

Disease modellingiPSC-derived cardiomyocytes

Patient- and mutation specific cardiomyocytes

Contraction

Electrophysiology

Calcium transients

Normal LQTS

Analysis of cardiomyocytes

Cardiac adverse effects (”ECG” of a cell)

Baseline

Drug-X 3 µM

Drug-X 15 µM

Pharmaceutical industry

Kuusela J et al, 2016

Personilized medication

� Same disease

� Same gene

� Different mutation

� Different drug response

� iPSC-derived cell reproduce thedrug response

Arrhythmiasabolished

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

Traditional vs stem cell-baseddrug discovery

New medication

Cell therapy

Personilizedmedication

Stem cells in medicine

Gene surgery

Disease-modelling

Cell tranplants

New drugs

Gene modification

Thank you!