First off, what are stem cells?
Stem cells are the earliest precursors to all the cells in our bodies. They can self-renew and mature into the various cells the body needs. There are several types of stem cells, ranging from pluripotent to totipotent to multipotent, and the types of stem cells your body produces depend on how old you are, and what kind of cells your body needs.
Embryonic stem cells, for example, are a category of pluripotent cells that can differentiate into any cell needed by a developing embryo, from those that form the placenta to those that make up the heart. However, not all stem cells have this impressive range. The most common type of stem cells in adults are multipotent, and these cells have a less varied range into which they can mature. They primarily develop into skin and muscle cells, replacing damaged or dying tissues throughout the body. Unfortunately, they cannot be used to regrow organs or a lost limb.
Why should we care about stem cells?
Research into using stem cells to treat different diseases and disorders is currently very sought after, potentially offering solutions to numerous medical challenges.
In 2006, Dr Shinya Yamanaka and his team made a massive breakthrough in stem cell research by creating induced pluripotent stem cells (iPSC). By taking regular adult fibroblast cells (cells that make up the connective tissue in the skin), scientists could wind back the clock on their stages of development, creating pluripotent stem cells capable of differentiating into a broader range of cells.
These stem cells have been used in trials for various diseases, the first of which was macular degeneration, a disease where a patient’s vision slowly deteriorates over time. In a 2014 trial, an iPSC treatment showed signs of success, with the patient’s visual function slightly increasing a year after the operation. Unfortunately, this procedure did not completely correct the patient’s vision, but it did improve their overall quality of life and ability to see.
The major issue with using iPSC’s in treatment, and why many trials have been halted, is the cost of the procedures. From initially harvesting the somatic cells (cells in the body other than sperm/egg cells) to reprogramming and inserting them, cost the developers approximately 1 million USD. Additional challenges such as potential rejection of the stem cells and post-operative infections could also complicate potential treatments.
Recent developments in iPSC research
The creation of iPSC-derived model organisms (aka Organoids) has allowed researchers to model diseases and cell development in a more natural and accurate environment, instead of studying isolated cells in a petri dish. Organoids are essentially artificial organs, grown in the lab under conditions mimicking that of the body’s natural internal environment. Human brain organoids have provided valuable insights into the effects of the Zika virus, revealing that it reduces neural stem cell proliferation and hinders normal brain cell development in foetuses. To be able to model a disease such as this paves the way for other complex brain diseases to be researched, and it need not be restricted to the brain alone. While the costs of creating these organoids remains a challenge, ongoing advancements are expected to reduce future expenses.
Advances in embryonic stem cell research
IPSCs are all well and good, but stem cell research is ever-developing, and scientists are now turning their eyes to a new pathway: synthetic embryonic stem cells.
In 2022, scientists programmed adult mouse stem cells to self-arrange into an embryo-like structure, complete with a partial digestive system and a beating heart. As these structures were formed without the fertilisation of an egg cell, they are termed ‘synthetic’ embryos.
Despite this exciting progress, it isn’t yet totally foolproof. Only 0.5% of the small clusters of stem cells combined to form the synthetic embryos, which is a fairly small success rate. However, when compared to normal mouse embryos, they were 95% identical in their genetic makeup and structure. Scientists believe that using these synthetic embryos will reduce the need for animal experimentation, though ethical concerns about their creation persist.
Similar synthetic embryos have been created using human cells, offering potential treatments for diseases like leukaemia and the possibility of growing tissues for transplantation which would certainly reduce the need for donors and issues of tissue rejection.
Ethical considerations: Are we playing God?
There are many controversies surrounding the use of harvested or donated embryonic stem cells, mainly that these cells have the potential to develop into a live organism, and that it would be unethical to perform experiments on these primordial forms of life. A resolution to this is to take the same approach as scientists did with mice, of reverting somatic cells to their precursor embryonic stem cell forms, and forming a synthetic embryo via these cells clustering together. This method may lessen ethical dilemmas, as somatic cells are more abundant and less controversial than embryonic stem cells. However, as of writing this article, no group of researchers have yet managed to create human synthetic embryos using this method.
A UK government committee in 1984 decreed that human embryos grown in the lab should be destroyed 14 days after fertilisation to prevent more ethical concerns from arising. Janet Rossant, a developmental biologist from Toronto’s Hospital for Sick Children stated that “For a start, it would be difficult to apply the 14-day rule in the same way” to synthetic embryos, simply because of how difficult it is to know when to start the timer. As these embryos are never actually fertilised, it complicates the decision of when the ‘potential for life’ has been reached.
The synthetic embryos that have already been created raise the question of whether they could develop into viable forms of life. However, when synthetic mouse embryos were implanted into the womb of a live mouse, they did not develop into foetuses, leaving the fate of human synthetic embryos uncertain. If perfected, human synthetic embryos could provide a solution to the infertility issues that some face. Following the ethical guidelines already set out, the usage of synthetic embryos in this way would be illegal. There has been research into creating egg cells from somatic cells, which would present less ethical concerns, as these cells begin as normal cells in an adult’s body, and do not originally have the potential for life. This is not a procedure currently available to treat infertility, but it may well become one in the future.
Up until July 2024, these recently created human synthetic embryos lay outside the regulation laws regarding the use of stem cells and models of human embryos. But because of the creation of an embryo with a heartbeat and blood circulation, a new code of practice is being put in to ensure that British researchers are being responsible with their experiments.
There is much work to be done in the sector of stem cells in the coming years, from developing methods of creating stem cell models and treatments to solidifying the ethics and moral considerations of using these cells. As we continue to explore this rapidly evolving area, we may soon realise the full potential of stem cell research: it could redefine the future of medicine and science.
