Autologous approaches to tissue engineering Beatrice Dionigi a,b , Dario O. Fauza a ,* a Dept. of Surgery, Boston Children's Hospital and Harvard Medical School b Dept. of Surgery, Brigham & Women's Hospital and Harvard Medical School STUDENT: 黃黃黃 INSTRUCTOR: 黃黃黃黃黃 1
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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
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.
• 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
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