Title: Using Tissue Engineering to Produce an Unlimited Supply of Tissues and Organs
1Using Tissue Engineering to Produce an Unlimited
Supply of Tissues and Organs
- Michael V. Sefton
- Institute of Biomaterials and Biomedical
Engineering, University of Toronto
IABG Conference Cambridge, UK Sept 19, 2003
2Tissue Engineering
cells
new organs
materials
3Living skin replacement
4Restore, maintain and improve tissue function
5Seed porous scaffold with cells
cardiomyocytes
0.3 mm
endothelial cells
porous scaffold
6Put scaffold in a bioreactor
impeller
bioreactor
growth medium
scaffold seeded with cells
7Cells grow and organise within scaffold
capillary network
cardiomyocytes
8Tissue Engineering is .. engineering healing
the persuasion of the body to heal itself,
through the delivery to the appropriate sites of
molecular signals, cells and supporting structures
Williams, Dictionary of Biomaterials, 1999
9To Engineer Healing
Tissue Replacement cells grown in culture and
seeded into material
Tissue Control material induces specific response
in vivo e.g., bonding, vessels
10Tissue Engineering applied developmental biology
Tissue Engineering (or RM) involves the
recapitulation of the steps of embryological
development
11Synonyms?
Tissue engineering Regenerative medicine
12The three Rs
- Replace
- make replacement safer, more effective and more
widely available - Repair
- repair tissues and organs, eliminating the need
for replacement - Regenerate
- repair tissues through regeneration
Shaf Keshavjee, 2003 NET proposal
13Convergence
Biomaterials Tissue Engineering
Stem cells cell therapy
Regenerative Medicine
Gene therapy
E3LSI Commercialisation
14Regenerative Medicine
. uses cells, soluble and matrix bound factors
and supporting structures or medical devices to
regenerate damaged tissue/organ structures and
function
15Potential demand is large
Pharmaceutical products 400 billion 300 billion
8 of world healthcare costs
Lysaght OLoughlin (2000) or US Spinal Injury
Centre
16Tissue Engineering a Heart
Nature Feb 27, 2003
17Hearts in a Box
- Unlimited supply
- Eliminate ethical issues associated with limited
resource - Spin-offs
- all components
- cells, patch, valve etc
- Ageing population
University of Toronto Bulletin
18Cardiovascular Procedures(AHA inpatient 1997)
19Spin-offs
20Spin-offs
cells for in situ repair
disease models
21Objective
- Produce an unlimited supply of human vital organs
- Enable ageing people to be active, healthy and
productive
adapted from Statistics Canada
22Critical IssuesBuilding a vital organ (heart)
23In situ repair - cardiomyocytes
Human cardiomyocytes stained for TN (triponon I)
Chiu et al, Ann Thorac Surg 60, 12-8, 1995
R-K. Li et al, Toronto
24In situ cardiomyoplasty
- Menasché et al , J Am Coll. Cardiol. 41, 2
April 2003, 1078-1083 Autologous skeletal
myoblast transplantation for severe
postinfarction left ventricular dysfunction - phase 1 trial with 10 patients as adjunct to
coronary bypass grafting - all with symptomatic improvement but 4 with
arrythmias - alternative cell sources, gene modification, ,
angiogenesis, remodeling effects?
25Growing Cardiomyocytes
Functional
polymer
10 µm
M.Papadaki, L.Freed, R.Langer Am.J.Physiol, Vol
277, H433-44 1999
26Mechanical Strength
LHeureux et al, FASEB J. 12, (1), 47-52, 1998
27Vascularisation
Adapted from, Nature 407, 2000
28Vascularisation strategies
Microfabrication
Growth factors
Inductive materials
Endothelial seeding
29Microencapsulation of Cells
cell-derived therapeutic agent (e.g., insulin)
immunoisolating perm-selective membrane
lymphocytes, antibodies, complement
extracellular matrix
Islets of Langerhans, genetically engineered
cells, liver cells
nutrients, growth factors, external stimulus
30VEGF Microcapsules
J. Vallbacka
31L929 capsules
Matrigel
capsule
capsule
Matrigel
capsule
25 ?m
100 ?m
non-transfected cells
32VEGF165 L929 cell capsules
Vessels in Matrigel
Vessels in skin
33Angiogenic Beads prepared by bulk polymerisation
- no (exogenous) growth factors
- angiogenic effect depends on biomaterial
chemistry - spin-off company - Rimon Therapeutics
www.rimontherapeutics.com
45 MAA
34Control Beads (PMMA)
PMMA Bead
Blood Vessels
Linear incision in normal rats (7 days)
35Angiogenic Beads (45 MAA)
45-MAA Bead
Blood Vessels
Linear incision in normal rats (7 days)
36Angiogenic beads under a full thickness skin
graft (rat)
10X
Factor VIII
20X
37(No Transcript)
38Rat skin graft (with panniculus carnosus, PC)
Necrosis
Thin muscle
39Skin grafts with angiogenic beads (rats)
Necrosis
Thin muscle
Control bead (MMA)
Angiogenic bead (45 MAA)
A. Eckhaus, 2003
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41Tissue Engineering a Heart
Nature Feb 27, 2003
42J.D. Power
43LIFE initiative collaboration
- Many institutions
- International
- All stakeholders
No single group or center has all the required
talents and expertise Pooling intellectual
resources is necessary
44Canadian Regenerative Medicine Network
Complex Tissue Organ Engineering
Development
Response
Host Acceptance
Functional Integration
Integration
45Canadian Regenerative Medicine Network
Adapted from PTEI 1997
46Master Tissue Engineer
Learn how to build complex structures from simple
ones
47Accenture
48Thanks to Canadian Institutes of Health
Research, NSERC, NIH