Meinhardt’s team at the Dresden University of Technology in Germany successfully grew spinal cord-like tissue using mouse embryonic stem cells (mESCs). Published in Stem Cell Reports, Meinhardt et al were able to achieve this by inducing organogenesis in a 3D synthetic matrix.
With this 3D scaffold and the right cocktail of neural inducers, they found that mESCs could self-organise into ‘neuroepithelial cysts’. These neural progenitors are small, round structures that grow into and form the embryonic spinal cord. Organs such as bladders and stomachs have been grown from stem cells before and even transplanted into patients. However, nervous tissue is considerably more challenging to generate, hence why this represents a significant step forward for regenerative medicine. This is because of the complexity of the structures involved as well as the highly organised and specific patterning of different cells across the structure.
Retinoic acid (a signalling molecule) was then added, activating other genes such as sonic hedgehog. The Sonic Hedgehog protein diffuses along the immature neural tube creating a concentration gradient. The concentration of the protein determines what a cell differentiates into, creating the specific patterning observed in the embryonic spinal cord. For example, cells nearest the bottom are exposed to the highest concentration of Sonic Hedgehog and develop into motor neurons. This process produces a number of different neurons along the gradient, recapitulating the events of embryonic development.
Stem cells are undifferentiated cells that divide symmetrically to produce two identical daughter cells – a process called self-renewal. They may also divide asymmetrically to produce a differentiated cell and another stem cell. Importantly, they are pluripotent meaning they have the potential to differentiate into any cell type in the body to build tissues, organs and whole organisms through self-directed morphogenesis. By taking advantage of this property, Meinhardt was able to influence the development of mESCs to produce complex tissue.
This unique ability offers the potential for regenerative medicine to produce healthy organs for patients who require transplantations as well as provide a model for studying organ development. Furthermore, therapies like this may be particularly productive because the human nervous system loses the ability to regenerate post-development.
To date, scientists have used stem cells to generate a number of different organs and even transplant them into patients with long-term success. At the moment, blood vessels and heart tissue generation is being progressed, while other stem cell transplantation procedures are already being met with success. For example, last month, a man paralysed from the chest down was able to walk again, following the transplantation of nerve cells from his nose into his spine. These nerve fibres were able to stimulate the growth of neurons and repair the spine.
Eventually, scientists aim to be able to reprogramme stem cells from adult skin cells, bypassing the need to extract them from embryos. This idea was awarded the Nobel Prize in 2006 when Yamanaka demonstrated that four specific transcription factors could convert a mature adult cell into a pluripotent stem cell. Additionally, these cells may be derived from a patient’s own cells, meaning a patient-matched stem cell line is created. As a result, organ transplants may be performed without chance of rejection because the body recognises the organ as native.
Stem cells are a valuable cell source for regenerative medicine techniques, for study and medical practice. Meinhardt’s work brings scientists closer to developing stem cells into mature human spinal cords that may be transplanted into patients. This work may be useful to researchers trying to develop such treatments, as well as learning more about repairing the human spine.
How might stem cells revolutionise medicine and how doctors are able to provide care in the future with this method of medicine?