Regenerative Medicine Strategies Flashcards
What is regenerative medicine?
Repairing and replacing lost tissues (from age/disease)
What is the problem with transplanting ES cells into lesions in an adult?
ES cells simply respond to signals from the environment. However, these signals have different functions in early development and adult. So, transplanted ES cells give rise to teratocarcinomas
What are the uses of adult stem cells in transplants?
They are lineage restricted so overcome many of the limitations of ES cells. They still pose a risk of tumours. However, degenerative diseases often affect tissues that don’t have proper stem cells
What is the problem with transplanting terminally differentiated cell types?
They don;t divide, so many cells will need to be transplanted. They are very unlikely to drive tumour formation since they don’t divide. Also, mature cell types often fail to integrate into a new environment
What is the benefit of transplanting progenitor cells?
They’re lineage restricted cells that can readily differentiate, but are only capable of a finite number of divisions so less likely to drive tumour growth
Why are organs transplanted and not just cell types?
Diseases often affect a whole area, affecting multiple different types of cell. Organ transplantations take care of that.
What are the two major limitations of organ donation?
Recipient must be immunosuppressed so that they don’t reject the organ, has long term effects
Limited number of organs available
How can we “overcome” the traditional problems associated with organ transplantation?
Transplant engineered tissues. We could generate required cell types ex vivo, assemble them, and transplant the whole organ. Could be patient’s own stem cells, or carefully selected cells from a large stem cell bank
How are HSCs used already in regenerative medicine?
Used in treatment plans for various cancers, haemoglobinopathies, inherited immune disorders, bone marrow failure, and some metaboic conditions.
Why are pluripotent stem cells so good for regenerative medicine?
Can be expanded indefinitely before transplantation - infinite supply of transplantable material
Can be generated (iPSCs) from patients - personalised medicine, no immunosuppression
Genetic engineering allows repairing of mutations present in the patients before the cells are differentiated
For multigenic diseases, we could have stem cell banks which would contain a cell for everyone requiring minimal immunosuppression
What does “pure” mean in terms of differentiating iPSCs in culture for transplantation?
No undifferentiated cells in the mix. Could form teratocarcinomas
What does “safe” mean in terms of differentiating iPSCs in culture for transplant?
They haven’t gained any new mutations in culture making them cancerous/dysfunctional
What does “at the right stage” mean in terms of differentiating iPSCs in culture for transplant?
They are mature cells. Usually differentiation starts with cells that resemble immature progenitors - be patient to get the mature cell
What are organoids?
Organ-like structures that self-organise in culture to resemble the tissue from which they are derived.
How would you grow a whole organ for a mouse, in a rat?
Inject mouse ES cells into a rat that lacks a gene essential for “pancreas” development. The rat grows because the mouse ES cells fill the niche left by the empty pancreas. This organ can be harvested
