The document discusses autologous approaches to tissue engineering using stem cells from various sources. It describes how mesenchymal stem cells from amniotic fluid proliferate faster than other sources and produce constructs with more glycosaminoglycans and elastin. Alternative MSC sources like amniotic fluid and adipose tissue are discussed as better options than bone marrow due to challenges with bone marrow isolation. Current clinical applications discussed include cardiovascular repair using autologous cells on biodegradable scaffolds, neural repair with fetal stem cells, skeletal muscle repair for Duchenne muscular dystrophy, urologic repair with tissue-engineered bladders, and airway reconstruction seeded with autologous cells. Future directions may see stem cell

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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