Stem Cells & Tissue Engineering Flashcards
When was the first stem cell therapy created and what was it?
1968 - bone marrow transplant
What 2 conditions must a cell fulfill to be classed as a stem cell?
Be capable of self-renewal
Give rise to multiple types of cells
What are stem cells classified on?
Differentiation potential (potency) Source
What are unipotent stem cells?
Cells that can only give rise to a single type of cell, make up the majority of the bodys cell types
What are multipotent stem cells?
Can give rise to multiple types of cells, are unable to generate all cell types of the 3 germ layers
What are pluripotent stem cells?
Can generate all cell types of the 3 germ layers (endoderm, mesoderm, ectoderm)
What are totipotent stem cells?
Only type of cell capable of producing and supporting the development of a whole organism (fertilised ovum)
4 germ layers (endoder, mesoderm, ectoderm and trophectoderm)
What type of stem cell is derived from adult tissue?
Multipotent - can be extracted from neural tissue, bone marrow, adipose tissue and blood etc.
Name the 2 different types of adult stem cells
Hematopoietic stem cells - present in bone marrow, produce blood cells and immune cells
Mesenchymal stem cells - found in multiple locations
Where are embryonic stem cells derived from?
Inner mass of a developing embryo (blastocyst)
What are induced pluripotent stem cells?
Artificially created stem cells
How are iPS made?
Unipotent cell from adult id taken, genes associated with the regulation of pluripotency are activated
What are the genes associated with pluripotency?
Oct3/4
Sox2
Klf4
C-MyC
How was the first iPS cell discovered?
Yamanaka’s team in Kyoto uni selected 24 genes shown to be important to ES cells, virally transfected inot adult mouse fibroblast, deleted genes 1 by 1 and identified 4 essential genes
Name 3 applications of stem cells
Bone marrow transplant
Potential therapies in development e.g. neuronal disorders, heart diseases etc.
Tissue engineering
What is tissue engineering?
An field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain or improve tissue function/whole organs
What are the 4 basic principles of tissue engineering?
- Reproduce whole organs or parts of the body for therapeutic use
- Address the problem of organ donation
- Remove the problem of organ rejection
- Produce bespoke organs that are biologically compatible with patient
What are the main steps of tissue engineering?
Biopsy Cell isolation Cell cultivation Cell proliferation Add scaffold Tissue development (growth factor & mechanical stimulus) Implantation
What 3 factors do most tissue engineering strategies employ?
- Biological source - the cells
- Supportive medium - replace extracellular matrix, the scaffold
- Environmental growth support - the bioreactor
Describe the steps of tissue engineering
- Extract cells from a tissue source e.g. bone
- Cells seeded onto an appropriate scaffold
- Grow implant in a bioreactor
- Reimplantation
What are the 4 sources of cells?
Autologous - obtained from the patient who will be reimplanted
Allogenic - from a donor
Xenogenic - from a separate species
Syngenic/isogenic - not currently acheivable
What are some advantages of autologous cells?
No risk of immune rejection
Biological activity perfectly matches activity of host
Lower risk of passing on pathogens/disorders
What is a disadvantage of using autologous cells?
Number of cells is low due to senescence and loss of function
What is senescence?
Cells only divide a certain number of times before stopping, if senescence isn’t functioning cancer occurs
What is contact inhibitions?
Cells can inhabit neighbouring growth if no room left, requires cells to be split apart which can cause damage
What are some advantages of using allogenic cells?
Greater number of cells
Off the shelf - cryopreservation for use when needed
What are some disadvantages of using allogenic cells?
Rejection by host immune system - fibroblasts have been used in skin engineering without rejection
Risk of pathogen/disorders being passed to host
What are some advantages of using xenogenic cells?
Greater number of cells - potentially limitless - using multiple donor organisms
Off the shelf - cryopreservation for use when needed
What are some disadvantages of using xenogenic cells?
Rejection by host immune system
Risk of pathogen/disorders being passed to host
Biocompatibility issues
What is the role of the scaffold in tissue engineering?
Provides a supportive structure designed to allow the desired biological mechanisms to occur
Name some materials used for scaffold production?
Biological source - extracted ECM or purified matric protein or polysaccharide materials
Polymer - wide variety used
Metals
What are some advantages of using a scaffold?
Doesn’t elicit an immune response
Many different ways of manufacturing them
Bioreabsorption is highly desired - material implanted is degraded over a defined period of time
Why is the environmental growth support needed?
Cells and biological constructs cultured in vitro require environmental support
e.g. bioreactor
What is a bioreactor?
Device designed to support a specific biological processes, cheaper if not used and less chance of harmful things being introduced
What is autologous chondrocyte implantation (ACI)?
Type of tissue engineering used to treat cartilage damage (injury not disease)
What are some problems associated with tissue engineering?
Replicating complexity
Issues of scale
Sources of cells - which is best for which organ?
Scaffold technology - approaches & materials
Economic costs - very expensive
