regenerative medicine

Question 1

what is regenerative medicine?

Answer 1

the idea you can replaced damaged cells in the body with stem cells

Question 2

what does regenerative medicine link?

Answer 2

tissue engineering, biomaterials and stem cell therapy

Question 3

what are the defining characteristics of stem cells?

Answer 3

• Undifferentiated
• Can divide indefinitely
• Self-renewing – can replace itself and expand the stem cell pool
• Give rise to progeny that differentiate into specialised cells

Question 4

what is pluripotent?

Answer 4

can differentiate into cells derived from any of the three germ layers

naturally occurs in the embryo

Question 5

what is totipotent

Answer 5

can differentiate into cells derived from any of the three germ layers or the placenta

Question 6

what is multipotent?

Answer 6

can give rise to several specialised cells or tissues of an organism (often tissue-specific – occur within differentiated tissues like bone marrow)

Question 7

what is oligopotent?

Answer 7

can generate a few cell types within a particular tissue

Question 8

what is unipotent?

Answer 8

can produce only one cell type but still capable of self-renewal

Question 9

what are haemopoietic stem cells?

Answer 9

multipotent stem cell that can give rise to bare cells

Question 10

what maintains and defines stem cells?

Answer 10

by the environment produced by surrounding differentiated cells

Question 11

what may differentiated cells do?

Answer 11

o secrete specific factors into the surrounding matrix

o communicate with the stem cells via gap junctions

Question 12

what can changes in a stem cell niche cause?

Answer 12

may induce a stem cell to die, divide or differentiate

Question 13

what is symmetric cell division?

Answer 13

produces 2 identical stem cells or 2 identical differentiated cells

Question 14

what does assymetric cell division produce?

Answer 14

stem cell and differentiated cell

Question 15

what are the ethical issues of using embryonic stem cells?

Answer 15

ethical issue of consent and killing the embryo

Question 16

what are the layers of the gastrula?

Answer 16

endoderm
mesoderm
ectoderm

Question 17

how are embryonic stem cells identified?

Answer 17

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

Question 18

what is the advantage of embryonic stem cells growing indefinitely in culture?

Answer 18

unlimited supply permits meaningful experiments

give rise to clinically relevant numbers

Question 19

how does a pluripotent embryonic stem cell turn into a large quantity of pure, mature cells?

Answer 19

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

Question 20

what are the challenges of ESC for transplantation therapies?

Answer 20

• Purity/production problems – v expensive to generate cells on a large scale in a sterile environment
• Cancer problems
• Immunology problems
• Ethics problems

Question 21

what is a teratoma? where are they found?

Answer 21

disorganised non-maligannt but aggressive growths consisting of tissue from 3 embryonic germ layers
• Usually found in ovaries and testis

Question 22

how are teratomas formed?

Answer 22

• Produced experimentally by the growth and differentiation of injected pluripotent embryonic stem cells.

Question 23

what are solutions for immune rejection in esc based therapy?

Answer 23

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

Question 24

how does therapeutic cloning?

Answer 24

• 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

Question 25

what are the advantages of therapeutic cloning?

Answer 25

• Ideal tissue for regenerative medicine because genetically identical to patient o circumvents problem of tissue rejection o model a patient’s specific disease

Question 26

what are the challenges of therapeutic cloning?

Answer 26

* 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

Question 27

explain how reproductive cloning happens?

Answer 27

* 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

Question 28

what are the ethics of reproductive cloning?

Answer 28

``` 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? ```

Question 29

what are clinical applications of ESCs?

Answer 29

trialled to cure blindness

Question 30

what are adult/somatic stem cells?

Answer 30

* 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

Question 31

what is the primary role of adult stem cells?

Answer 31

to maintain and repair the tissue in which they are found

Question 32

why are adult stem cells considered multipotent

Answer 32

* 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

Question 33

what are the advantages of adult stem cells for cell therapies?

Answer 33

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)

Question 34

what is bubble boy disease?

Answer 34

non-functioning immune system caused by mutated genes

Question 35

what therapy was developed to treat bubble boy disease?

Answer 35

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

Question 36

what are induced pluripotent stem cells?

Answer 36

• 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

Question 37

what are the advantages of iPSCs?

Answer 37

no need for embryos, circumvents immunological rejection

Question 38

what are the disadvantages of iPSCs?

Answer 38

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

Question 39

how can iPSCs be used in research labs?

Answer 39

- 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

Question 40

what is an example of iPSCs being used in drug development?

Answer 40

o Modeling Alzheimer’s Disease with iPSCs o Reveals different cell stress phenotypes o Differential drug responsiveness o Step toward ‘personalised medicine’