From an ethical and moral standpoint, list pros and cons of working with hiPSCs as opposed to embryonic stem cells?
Ethical considerations of Embryonic Stem Cells (ESCs)
Pros:
The advantages of ESCs in research and therapy are rather practical - they are probably the best models for research on human development and naturally pluripotent so that they can be developed into many tissues.
From some ethical viewpoints, including those that do not consider ESCs to be equal to a person, using ESCs for research and therapeutic purposes is a logical step that promises the possibility of tissue and organ regeneration and could safe the life, or the life quality of many people.
Cons:
The use of ESCs for research and therapeutic purposes, involves a couple of ethical concerns which can be summarized to:
A market and demand for ESCs could lead to the exploitation of women and a surge in illegal harvesting. This is especially critical, since eggs are harvested through very invasive procedures.
Some philosophical standpoints, specifically those that consider the the emergence of the one-cell zygote as start of human life, consider embryos as human beings, with interests and rights. Thus the act of destroying embroys to obtain ESCs is tantamaunt to taking a potential human's life. Although this viewpoint has been contested (the twin argument and empirical distinctions about the intercellular coordination of the zygote or the degree of nervous system development), a consensus on whether embroys do or do not have a moral status, or even an increasing status as it develops, has not been reached (yet).
Advances in cloning technologies could enable the pursuit of reproductive cloning.
Concerns in 2) also apply here. Some ethical views would equate research and therapy based on ESCs to humanitarian crimes.
How accessible are therapies based on ESCs to a variety of demographics and will they get more accessible as time goes on? Since ESCs are costly to generate, they might further exacerbate the inequality in healthcare and quality of life.
In summary, ethics and morals surrounding ESC research are very complicated and depending on which ethical standpoint is taken, the research on ESC can range from being a promising tool for the creation of therapies that can save countless lifes to being an crime against humanity.
Ethical considerations of Human induced pluripotent stem cells (hiPSCs)
Pros:
They are derived from adult cells - which for many is an advantage, since it doesn't require destroying embryos.
Feminist concerns regarding ESCs, which put an unequal burden on women as supplier of eggs, thus putting them in danger of exploitation, are thus alleviated as well. (Concerns about donor consent in general still apply though)
Cells are typically donated through non-invasive procedures
Acquiring hiPSCs is easier and less costly, which might make them available to the general public sooner (than ESCs).
Cons:
While many ethical concerns surrounding ESCs are eliminated with hiPSCs, there are still some remaining
hiPSCs, while similar to ESCs, do not reach the same potency, since they can not develop to a full embryo. However, once hiPSCs engineering advances so far that their potency extends to embryonal development, the same concerns surrounding ESCs with regards to humanity and personhood will apply to hiPSCs as well.
Genetic modification of the human genome. Some hiPSCs are genetically modified to reach a therapeutic goal. This could lead to a slippery slope to accidental or intentional introduction of potentially harmful genes (e.g. oncogenes), or even animal genes forming human chimeras.
If we are to use organoid models as surrogates for in vivo tissues, what type of functional attributes would be critical to add/engineer into such organoid systems?
Structural similarity, to model intra-organ, location dependent interactions
Representation of different cell populations. Organs are often divided into different functional units, which contain specialized cells
Organ metabolic homeostasis. The organoid should be kept under conditions that represent the metabolism of the organ (oxygenation level, nutrient availability, hydration, processing of metabolic products etc)
Can you think of any limitations in current organoid and or organ on a chip systems in recapitulating human biology?
The human biology has not been completely understood on a systematic and on population level yet. It is thus doubtful, whether the approximation to the human body by organoid systems is sufficient for certain scientific questions.
If you were to theorize an experiment about improving current organoid models, which aspects of the microenvironment would you consider adding beyond chemical?
Technically, everything is chemistry to some degree. In my answer I consider "chemical aspects" to be 1) chemicophysical properties, such as pH, oxygenation levels etc, as well as 2) small molecules like lipids, fatty acids, sugars, metal(ions) and some hormones.
This leaves me with growth factors and protein/peptide based hormones.
Additionally including members of the immunesystem that are present in the respective physiological organ microenvironment, might contribute to the accuracy of the organoic system.
In the tissue engineering paradigm, what properties are important to provide from a scaffold and bioreactor?
In this exercise we have the opportunity to contribute to the experimental setup for an EHT drug screening, by deciding on the drugs to be tested, as well as their concentrations and dosing.
We were asked to briefly hypothesize how each of these drugs would affect the heart and make our selection based on that.
Further we then asked to discuss how we would select “appropriate” concentrations to work with and what the current standard in drug screening are in determining drug concentrations for clinical settings (e.g. EC50).
Once the EHTs are treated with the selected drugs, we will be provided with microscopy recordings where our objective will be to analyse and calculate the displacement of the micropillars and ultimately active/contractile force using either ImageJ, Matlab, etc.
Based on these calculation we would then conclude whether the compounds had worked as theorized and evaluate our experimental setup.
We were able to choose from the following drugs: