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Using Tissue Engineering to Produce an Unlimited Supply of Tissues and Organs

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Title: Using Tissue Engineering to Produce an Unlimited Supply of Tissues and Organs


1
Using 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
2
Tissue Engineering
cells
new organs
materials
3
Living skin replacement
4
Restore, maintain and improve tissue function
5
Seed porous scaffold with cells
cardiomyocytes
0.3 mm
endothelial cells
porous scaffold
6
Put scaffold in a bioreactor
impeller
bioreactor
growth medium
scaffold seeded with cells
7
Cells grow and organise within scaffold
capillary network
cardiomyocytes
8
Tissue 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
9
To Engineer Healing
Tissue Replacement cells grown in culture and
seeded into material
Tissue Control material induces specific response
in vivo e.g., bonding, vessels
10
Tissue Engineering applied developmental biology
Tissue Engineering (or RM) involves the
recapitulation of the steps of embryological
development
11
Synonyms?
Tissue engineering Regenerative medicine
12
The 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
13
Convergence
Biomaterials Tissue Engineering
Stem cells cell therapy
Regenerative Medicine
Gene therapy
E3LSI Commercialisation
14
Regenerative Medicine
. uses cells, soluble and matrix bound factors
and supporting structures or medical devices to
regenerate damaged tissue/organ structures and
function
15
Potential demand is large
Pharmaceutical products 400 billion 300 billion
8 of world healthcare costs
Lysaght OLoughlin (2000) or US Spinal Injury
Centre
16
Tissue Engineering a Heart
Nature Feb 27, 2003
17
Hearts 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
18
Cardiovascular Procedures(AHA inpatient 1997)
19
Spin-offs
20
Spin-offs
cells for in situ repair
disease models
21
Objective
  • Produce an unlimited supply of human vital organs
  • Enable ageing people to be active, healthy and
    productive

adapted from Statistics Canada
22
Critical IssuesBuilding a vital organ (heart)
23
In 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
24
In 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?

25
Growing Cardiomyocytes
Functional
polymer
10 µm
M.Papadaki, L.Freed, R.Langer Am.J.Physiol, Vol
277, H433-44 1999
26
Mechanical Strength
LHeureux et al, FASEB J. 12, (1), 47-52, 1998
27
Vascularisation
Adapted from, Nature 407, 2000
28
Vascularisation strategies
Microfabrication
Growth factors
Inductive materials
Endothelial seeding
29
Microencapsulation 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
30
VEGF Microcapsules
J. Vallbacka
31
L929 capsules
Matrigel
capsule
capsule
Matrigel
capsule
25 ?m
100 ?m
non-transfected cells
32
VEGF165 L929 cell capsules
Vessels in Matrigel
Vessels in skin
33
Angiogenic 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
34
Control Beads (PMMA)
PMMA Bead
Blood Vessels
Linear incision in normal rats (7 days)
35
Angiogenic Beads (45 MAA)
45-MAA Bead
Blood Vessels
Linear incision in normal rats (7 days)
36
Angiogenic beads under a full thickness skin
graft (rat)
10X
Factor VIII
20X
37
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38
Rat skin graft (with panniculus carnosus, PC)
Necrosis
Thin muscle
39
Skin grafts with angiogenic beads (rats)
Necrosis
Thin muscle
Control bead (MMA)
Angiogenic bead (45 MAA)
A. Eckhaus, 2003
40
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41
Tissue Engineering a Heart
Nature Feb 27, 2003
42
J.D. Power
43
LIFE initiative collaboration
  • Many institutions
  • International
  • All stakeholders

No single group or center has all the required
talents and expertise Pooling intellectual
resources is necessary
44
Canadian Regenerative Medicine Network
Complex Tissue Organ Engineering
Development
Response
Host Acceptance
Functional Integration
Integration
45
Canadian Regenerative Medicine Network
Adapted from PTEI 1997
46
Master Tissue Engineer
Learn how to build complex structures from simple
ones
47
Accenture
48
Thanks to Canadian Institutes of Health
Research, NSERC, NIH
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