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Summary Lectures Trends in Stem Cell Biology
- Instelling
- Radboud Universiteit Nijmegen (RU)
All the lectures from trends in stem cell biology are in this document.
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Trends in Stem Cell Biology – LecturesLecture 1 – 8-09-21
Subjectivism in Ethics → ethical subjectivism is the idea that moral opinions are based on our feelings
and nothing more. On this view, there is no such things as ‘objective’ right and wrong.
- Subjectivism is making stammering blocks, because in the end we are making decisions.
What in the past was considered a medical enhancement, is now considered purely medical because
the norms of what it means to be healthy shifts.
This leads in ethics to the normativity discussion, so what is normal?
What are Ethical theories?
- Explain what makes an action right or wrong
- Ethical theories vs particular ethical judgements
- Analogy with scientific theories and observations
Ethics ≠ Morals!
- Morals are your personal opinions.
Ethics ≠ law !
- Law is the translation of the average morality of a society
*in ethical discissions the answer can not be based on science, because for example there is a
discussion for a third shot of the covid vaccine, but in poor countries there are a lot of people who
did not even had a first vaccine. This is a moral situation, and not science.
Some kinds of ethical theory:
- Consequentialism → the rightness/wrongness of an action is determined by its
consequences. Action → result
o Example: utilitarianism. The right action is the one that promotes the greatest
happiness of the greatest number (maximizes social utility)
o Another example= ethical egoism. The right action is the one that promoters the
greatest happiness of the agent. (maximizes the agent’s utility)
▪ Concentrate on the agent, on the individual. The right action is the one that
makes ‘me’ the happiest. → if everybody individually is happy, that means
that the whole community is happen.
o The problem with consequentialism is that you never know if your are missing
something essential, by building up your arguments.
- Deontology→ the rightness/wrongness of an action is determined by inherent features of
the action itself, or by an inherently valid rule. Rule → action.
o If an action is the wrong kind, it is forbidden, no matter how good its consequences
are. → rejects both utilitarianism and ethical egoism.
o ‘the end doesn’t justify the means’
o Example; ‘tien geboden’
o Example: Kantianism. Right actions must be universalizable and must treat rational
agents as ends, not mere means (trade-offs forbidden) → Immanuel Kant
- Virtue ethics → the rightness/wrongness of an action is determined by the character traits it
expresses. Character → action
o Emphasize what kind of person you should be
o Examples: Aristotelianism, Confucianism
- Contractarianism
, - Natural law
- Relativism
Lecture 22-09-2021
According to Wikipedia; stem cells are biological cells that can differentiate into other type of cells
and can divide to produce more of the same type of stem cells (self-renewal).
In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from
the inner cell mass of blastocysts and adult stem cells.
this is the development of a mouse
embryo. The first stages are just dividing of
the cells, then the cells are totipotence,
they can form anything. Then in G you can
see that there is a blastocyst formed and
then later there is also the trophoblast
(trophectoderm) formed. This
trophectoderm will develop into the
placenta. The epiblast will develop into the
organism. So this means that earlier one in the process, cells have to choose which way to will go, so
to develop the placenta or the organism. And what is known, is that once these cells have chosen to
form the placenta they cannot go back to form for instance the inner cell mass. So first the cells are
totipotent and then they are pluripotent.
Then further in the development the epiblast cells need to form into the ectoderm, endoderm or
mesoderm lineage. And this commitment to one type of lineage is irreversible, so cells cannot go
back and form another lineage.
totipotency: trophoblast and inner cell mass (not
necessarily the most interesting cells; can also form
extraembryonic tissue).
Pluripotency (embryonic stem cells): capable of
differentiation into all the three germlayers
(ecto,endo-,mesoderm)
Multipotency: progenitor cells (hematopoetic stem
cell)
Oligopotency: e.g. myeloid stem cell (not lymphoid
lineage)
Unipotency: differentiate into one cell only.
*multi -oligo and uni are adult stem cells
Reprogramming and trans-differentiation have been developed in vitro (so for example making from
a muscle cell a neuron cell), but are likely not wide-spread in vivo.
Conclusion → cells loose potency during in vivo development
There are five different types of pluripotent cells:
1. Embryonic stem cells (ESCs)
2. Epiblast stem cells (EpiSCs; primed ES cells)
3. Embryonal Carcinoma Cells (ECs; from teratocarcinoma in mouse testis from primordial germ
cells (PGCs))
4. Embryonic germ cells (EGCs)
5. Induced pluripotent stem cells
(iPSCs)
, Test for pluripotency for newly derived cell lines:
- You might want to show that these cells can differentiate into the three germ layers, since
that is a characteristic of pluripotent cells
o Or you inject them into an embryo and see that they indeed contribute to all the
different lineages.
- You can also show that they will extensive proliferate, because that is another characteristic,
since they do self-renewal.
- Possibility is to take one cell and show that they will grow out to a full organism.
- Teratomas → take one pluripotent cell and put it under the skin, then it will differentiate into
the three different layers
*these things are done with mouse → ethical discussion is how far can you go with humans
Humans test:
- Multilineage differentiation in vitro (vivo NOT) (germline colonization)
- Normal, stable karyotype
- Extensive proliferation in vitro, under well-defined culture conditions
- Known marker genes/proteins (Oct4, Nanog, Sox2, SSEA, etc)
In practice absolute proof: NOT: contribute to all somatic lineages/produce germ line (chimerism).
Teratomas with differentiated cells of all three germ layers (could be performed in mice: ethical
discussion).
Why are ES cells so interesting?
- Pluripotent, self-renewal → ES cells are the only one that will form the complete body
- Model for embryonic development
- Regenerative medicine → the cells grow in large quantities and then can differentiate, and
then they can replace the lost cells (for example use nerve cells to treat Parkinson)
- Generation of KO mouse → so compare a wildtype mouse with a mouse that has a knockout
of one gene, and then you can see if that gene is of great importance of not.
- Disease model, because differentiate into desired specialisation → so watch how certain
defects in the development lead to a disease
- Cytotoxicity tests → especially during pregnancy for foetus
*again ethical discussion
Replace lost cells, might be useful in:
- Stroke (heart attack) → loss of muscle cells
- Duchenne muscular dystrophy → muscle cell degeneration (eventual death)
- Parkinson’s disease → loss of dopamine-generating cells in the substantia nigra, a region of
the midbrain
- Alzheimer
Dangers:
- Graft rejection (but not when it’s from the patient itself: cord blood)
- Graft-vs-host
- Teratocarcinoma
The pluripotency network acts to;
- Self-induce its own expression, and of other pluripotency genes, by binding in the promotor
- Repress genes that induce differentiation
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