1Autologous approaches to tissue engineeringBeatrice Dionigia,b,Dario O. Fauzaa,*

aDept. of Surgery, Boston Children's Hospital and Harvard Medical SchoolbDept. of Surgery, Brigham & Women's Hospital and Harvard Medical School

STUDENT: 黃德偉INSTRUCTOR: 劉麗芬教授

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Introduction

Adopted from :Wikipedia

Stem cell(MSC,ESC,iPS….)

FBS（ Fetal Bovine Serum)

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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

Fig 1. Typical gross appearance of a tubular cartilaginous construct engineered from amniotic mesenchymal stem cells.

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Cell sources

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.

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Translational challenges

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 

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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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Cont…

Unsustainable in the long runNumber of companies still continue to invest in the

development of new products via healthy partnership between academia and industry 

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Current clinical applications

Cardiovascular repairNeural repairSkeletal muscle repairUrologic repairAirway reconstruction

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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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Cardiovascular repair

After using autologous bone marrow mesenchymal cells 

Increased myocardial fluorodeoxyglucose uptake

Enhanced wall motion Reduction in ventricular end-systolicEnd-diastolic volumes 

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.

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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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Neural repair

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

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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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Skeletal muscle repair

Dystrophin-positive fibers comprised up to 36 percent of the injected muscles after 1 month 

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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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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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Airway reconstruction

Protracted time required to fabricate these constructs

Nano-composite polymer and growth factor-induced endogenous stem cell

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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

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

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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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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