regenerative medicine Flashcards
what is regenerative medicine?
the idea you can replaced damaged cells in the body with stem cells
what does regenerative medicine link?
tissue engineering, biomaterials and stem cell therapy
what are the defining characteristics of stem cells?
- Undifferentiated
- Can divide indefinitely
- Self-renewing – can replace itself and expand the stem cell pool
- Give rise to progeny that differentiate into specialised cells
what is pluripotent?
can differentiate into cells derived from any of the three germ layers
naturally occurs in the embryo
what is totipotent
can differentiate into cells derived from any of the three germ layers or the placenta
what is multipotent?
can give rise to several specialised cells or tissues of an organism (often tissue-specific – occur within differentiated tissues like bone marrow)
what is oligopotent?
can generate a few cell types within a particular tissue
what is unipotent?
can produce only one cell type but still capable of self-renewal
what are haemopoietic stem cells?
multipotent stem cell that can give rise to bare cells
what maintains and defines stem cells?
by the environment produced by surrounding differentiated cells
what may differentiated cells do?
o secrete specific factors into the surrounding matrix
o communicate with the stem cells via gap junctions
what can changes in a stem cell niche cause?
may induce a stem cell to die, divide or differentiate
what is symmetric cell division?
produces 2 identical stem cells or 2 identical differentiated cells
what does assymetric cell division produce?
stem cell and differentiated cell
what are the ethical issues of using embryonic stem cells?
ethical issue of consent and killing the embryo
what are the layers of the gastrula?
endoderm
mesoderm
ectoderm
how are embryonic stem cells identified?
Immortality, clonality, undifferentiated and wide developmental potential
grow indefinitely in culture in the primitive embryonic state
• Maintain normal karyotype and expression of telomerase
• Presence of markers that are only found in undifferentiated cells
• Able to differentiate into a wide range of cell types in vitro and in vivo
what is the advantage of embryonic stem cells growing indefinitely in culture?
unlimited supply permits meaningful experiments
give rise to clinically relevant numbers
how does a pluripotent embryonic stem cell turn into a large quantity of pure, mature cells?
ES cell gets signal for commitment
turns into committed progentior cells
selection and expansion of these cells
then there are signals for growth and differentiation
turns into a large quantity of pure mature cells
what are the challenges of ESC for transplantation therapies?
- Purity/production problems – v expensive to generate cells on a large scale in a sterile environment
- Cancer problems
- Immunology problems
- Ethics problems
what is a teratoma? where are they found?
disorganised non-maligannt but aggressive growths consisting of tissue from 3 embryonic germ layers
• Usually found in ovaries and testis
how are teratomas formed?
• Produced experimentally by the growth and differentiation of injected pluripotent embryonic stem cells.
what are solutions for immune rejection in esc based therapy?
large banks of ES cells with as many MHC complexes as possible v expensive tho
manipulation of histocompatibility genes in ES cells
replacement of hematopoietic tissue of patient with ES-derived cells prior to graft
immunosuppressive drugs or antibodies
therapeutic cloning
how does therapeutic cloning?
- Isolate cell
- Remove nucleus from unfertilised egg
- Initiate development of nucleus in the empty egg through an electric shock
- Forms Blastocyst
- Create embryo stem cell line that’s custom-made ES cells – pluripotent, immortal, genetically identical to the adult cell nucleus
what are the advantages of therapeutic cloning?
• Ideal tissue for regenerative medicine because genetically identical to patient
o circumvents problem of tissue rejection
o model a patient’s specific disease
what are the challenges of therapeutic cloning?
- Percentage of successful clones is low – long time-frame to generate
- Creating potential embryo (not fertilized) for research/treatment
- Practical - source of oocytes? Should women donate for such research/treatments?
- Slippery slope to reproductive cloning
explain how reproductive cloning happens?
- Isolate cell from the mother and remove nucleus
- Remove nucleus from an unfertilised egg
- Take mother’s nucleus and put it in the unfertilised egg diploid oocyte
- Diploid oocyte acts like a fertilised egg and is implanted into surrogate mother
- Leads to a cloned mouse – genetically identical to starting mouse
what are the ethics of reproductive cloning?
o Are humans playing God? o Will embryo farms be around in the future? o Will healthcare costs skyrocket? o Is it morally right? o Are embryos alive?
what are clinical applications of ESCs?
trialled to cure blindness
what are adult/somatic stem cells?
- Rare, undifferentiated cells found among differentiated cells in a tissue or organ
- Capable of differentiating to produce the major specialised cell types of the tissue
what is the primary role of adult stem cells?
to maintain and repair the tissue in which they are found
why are adult stem cells considered multipotent
- Can only make the kinds of cells in the body that they belong to
- Multipotent bc they can make multiple types of specialised cells – but not ANY types of cells
what are the advantages of adult stem cells for cell therapies?
no legal or ethical concerns
- patient’s own cells –> no immunological rejection
- wont lead to tumour formation
- can learn how to repair ourselves –> avoid problem of cell transplant
- proven to be theraputically effective in skin grafts (although skin grafts dont have the same function as normal tissue)
what is bubble boy disease?
non-functioning immune system caused by mutated genes
what therapy was developed to treat bubble boy disease?
o “Repair and replace” strategy
o Remove stem cells from a patient’s bone marrow
o Transfer a correct copy of the defective ADA gene.
o Replace cells
what are induced pluripotent stem cells?
• Somatic cell is genetically reprogrammed by adding certain genes to the cell.
• Causes it to behave like an embryonic stem cell
- can be cultured in a lab
what are the advantages of iPSCs?
no need for embryos, circumvents immunological rejection
what are the disadvantages of iPSCs?
o Reduce risk of cancer
o Remove the requirement for viral integration
o Demonstrate long-term stability of re-programmed cells
o Improvement of technical efficiency
how can iPSCs be used in research labs?
- used in drug development and toxicity tests
- used to study development and gene control
- used for therapy –> bone marrow, nerve cells, heart muscle cells and pancreatic islet cells.
- research tool, diagnostic tool and therapeutic assessment
what is an example of iPSCs being used in drug development?
o Modeling Alzheimer’s Disease with iPSCs
o Reveals different cell stress phenotypes
o Differential drug responsiveness
o Step toward ‘personalised medicine’
