Autologous approach to tissue engineering

1. Autologous approaches
to tissue engineering
Beatrice Dionigia,b,
Dario O. Fauzaa,*
aDept. of Surgery, Boston Children's Hospital and Harvard Medical
School
bDept. of Surgery, Brigham & Women's Hospital and Harvard Medical
School
STUDENT: 黃德偉
INSTRUCTOR: 劉麗芬教授
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2. Introduction
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Adopted
from :Wikipedia
Stem cell(MSC,ESC,iPS….)
FBS（Fetal
Bovine
Serum)

3. Cell sources
 Mesenchymal stem cells (MSCs) procured from
amniotic fluid proliferate significantly faster in vitro
 Unusually rich in both glycosaminoglycans and α-
elastin, when compared with constructs originated
from these other MSCs, under equal bioreactor
conditions
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Fig 1. Typical gross appearance of a tubular
cartilaginous construct engineered from
amniotic mesenchymal stem cells.

4. Cell sources
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 MSC isolation and expansion from the bone
marrow is difficult (influenced by the donor's
age)
 Alternative sources of MSCs, such as the
amniotic fluid and adipose tissue
 Better translational appeal in many clinical
scenarios, when compared with bone marrow
Fig 2. Diagramatic
representation of the concept
of autologous amniotic
mesenchymal stem cell-based
fetal tissue engineering for the
treatment of congenital
anomalies.

5. Translational challenges
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Timing
•Involve weeks or
months
Infectious risks
•Requires
xenogeneic
products, fetal
bovine serum
•Can only
propagate
consistently on
xenogeneic feeder
layers
Synthetic
biomaterials
•Elastomers
•Nanostructures
•Biocompatible

6. Regulatory Challenges
 Slow approval clinical translation of many tissue
engineering therapies processes
 Demands for unique safety data sets(genomic
stability, tumorigenesis)
 American biotechnology companies have
engaged in collecting clinical data overseas, at
lower costs, as most other countries have less
stringent regulatory procedures
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7. Cont…
 Unsustainable in the long run
 Number of companies still continue to invest in the
development of new products via healthy
partnership between academia and industry
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8. Current clinical applications
 Cardiovascular repair
 Neural repair
 Skeletal muscle repair
 Urologic repair
 Airway reconstruction
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9. Cardiovascular repair
 Congenital heart disease is the leading cause of
neonatal death from birth defects.
 Creating a cardiac total cavopulmonary connection
using a biocompatible synthetic conduit
 Prone to thromboembolism and infection, and do not
grow with the patient
 Autologous cells seeded on a biodegradable scaffold
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10. Cardiovascular repair
 After using autologous bone marrow
mesenchymal cells
 Increased myocardial
fluorodeoxyglucose uptake
 Enhanced wall motion
 Reduction in ventricular end-systolic
 End-diastolic volumes
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Fig 3. Growth potential of
human engineered
vascular grafts. A)
Magnetic resonance
image (MRI) 9 months
following implantation. B)
Three-dimensional
computed tomography
(CT) angiogram one year
after implantation. Red
arrows indicate location of
the implant.

11. Neural repair
 Parkinson's disease is a prevalent and debilitating
neurodegenerative disorder
 Transplantation of human fetal ventral
mesencephalic dopaminergic cells
 High capacity for self-renewal
 Supply an abundant number of specialized neurons
for the treatment
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12. Neural repair
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Adopted from :
Seeking regulatory
approval for phase II
clinical trials of a
strategy that includes
neural stem cell-
derived dopaminergic
cells delivered into the
affected striatal
structures of patients

13. Skeletal muscle repair
 Duchenne muscular dystrophy (DMD) is an X-linked
genetic disorder
 Results in chronic injury to skeletal myocytes, leading
to a vicious cycle of myocyte degradation and
fibrosis
 Treatment of DMD: Myoblast Transfer Therapy (MTT)
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14. Skeletal muscle repair
 Dystrophin-positive fibers comprised up to
36 percent of the injected muscles after 1
month
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15. Urologic repair
 Traditionally relied on the use of heterotopic
autologous grafts (stomach, intestine,colon)
 Significant morbidity eg ( urolithiasis, metabolic
disturbances, and malignant degeneration)
 Neo-Bladder AugmentTM ( only in a phase I trial)
 Due to the limited to no clinical efficacy and the
occurrence of serious adverse events
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16. Airway reconstruction
 Tracheal reconstructions remain frequently
associated with suboptimal functional results and
substantial morbidity and mortality
 Its structure and biomechanical properties are in fact
quite complex and demanding
 Usually seeded with autologous bronchial epithelial
cells and bone marrow-derived MSCs and/or
differentiated chondrocytes
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17. Airway reconstruction
 Protracted time required to fabricate these
constructs
 Nano-composite polymer and growth factor-
induced endogenous stem cell
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18. Future perspectives
 Tissue engineering remains in the early phase of its
developmental curve
 Much slower pace than what we can expect for the
future
 Stem cell-based tissue engineering reaching
conventional clinical practice, from fetal medicine to
geriatrics and the entire gamut in between
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19. 問題
1.請問上述所講的哪個是無機生物材料？(宗軒)
A:PLGA
B:PEG
C:RADA16-Ⅰ
D:Bioceramics
2.以蛋白質為基質所做支架，最常用的是哪種蛋白？(景皓)
Ａ：膠原蛋白
Ｂ：絲蛋白
Ｃ：纖維蛋白
Ｄ：肌動蛋白

20. 3.What are the advantages biologically-derived materials
and acellular matrices?
A)Can deliver molecules that affect regeneration
B)Reproducibility in production
C)Large scale production
D)Can be tailored to a particular application such as
mechanical properties, degradation rate, microstructure
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21. 4.哪一個敘述對於臍帶血移植有誤?(祺舜)
A.採取臍帶血時候，具有侵入性的危險
B.臍帶血移植配對稱成功機率比骨髓移植還高
C.臍帶血具有較低的宿主排斥性
D.臍帶血的HSCs的含量會少於骨隨裡面的HSCs含量
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