Human embryonic stem cells come from human embryos in the early stages of development. In embryos, stem cells are the building blocks for the whole organism that transform into countless distinct cells, which are then used to build organs with distinct functions. The same developmental potential is present in human embryonic stem cells growing in Petri dishes. This ability gives them an almost “miraculous” quality and the medical community has high hopes for their potential use in treating diseases and serious injuries.
A team from the Department of Histology and Embryology at the Masaryk University Faculty of Medicine is now working with the Center of Assisted Reproduction at the University Hospital Brno and the FNUSA-ICRC Cell and Tissue Engineering Facility Research Group to prepare human embryonic stem cell lines of a sufficient quality to be used in human application. Stem cell lines are essentially reservoirs of cells created by perpetual propagation of a small original group of embryonic stem cells, which can be stored in laboratories for many years.
Human embryonic stem cells have unlimited capacity to divide, their genetic information does not change over time, and they can develop into a whole range of specialised human cells (of which there are at least over 200). Under laboratory conditions, embryonic stem cells can be induced to develop into specialised human cells. These specialised cells are then used in research, which studies their potential use to repair damage to the human body from specific diseases or injuries. Any tissue or organ, from bones to pancreas to the brain, is a potential target.
“As researchers, we already have sufficient knowledge to launch clinical trials of embryonic human stem cell therapy. We also want to keep abreast with the latest developments abroad and make sure that any future treatments are available to Czech patients as soon as possible,” says Aleš Hampl, head of the Department of Histology and Embryology at Masaryk University, when referring to the objectives of this project, which is funded by the Czech Ministry of Health.
The task ahead of the researcher is to obtain suitable embryos donated by the parents for this purpose and to refine the methods needed to establish the embryonic stem cell lines and to perform the other necessary steps, such as propagation, evaluation, and storage. Moreover, all these steps have to be certified by supervisory authorities, such as the State Institute for Drug Control, to satisfy all legal and regulatory requirements in the Czech Republic and abroad.
Ethical and technical concerns
While the project is technically complex, it is the ethical aspects that are the most complicated part. “Obtaining suitable embryos is a challenging issue. We can only use embryos that were originally created for the purposes of fertility treatment and then were not used, and only with the couple’s consent.”
Human embryonic stem cells
Since the embryonic stem cells could potentially be used to treat thousands of patients, the donors must sign away all rights and control over the cells derived from their embryo and must meet strict requirements with regard to their health. Despite this, Hampl says that people in the Czech Republic have been very willing to donate their embryos for this purpose.
However, these are not the only obstacles to the therapeutic use of embryonic stem cells. As in the case of organ transplants, genetic and immune compatibility with the potential recipient is key.
“While the immunogenic properties of embryonic stem cells differ from the properties of a mature organ or blood cells – which means that the reaction of the body may be much more muted, or there might be no reaction at all – the cells can still affect the recipient. This is one of the reasons why it is better to have more than one stem cell line that can be used to prepare the medicinal product,” says Hampl.
Medicinal products in just a few years
The Brno team plan to create at least three lines from three different embryos as part of the project. “This is not intended to cover all the immunological variations, but rather to prove that we have mastered the preparation process,” adds Hampl.
These lines can then be used to create cells for clinical trials, which verify the safety and efficacy of the treatment for specific diagnoses. This means that there is still a long way to go, but as Hampl explains, if the clinical trials are successful, the first medicinal products derived from human embryonic stem cells could be available within a few years.
Several clinical trials using stem cells are already underway in the Czech Republic. However, these trials work with different types of cells. These are mesenchymal stem cells, which are found in various places in the body where they help replenish tissues although the process is still not fully understood. These cells can also be propagated in the lab but can only transform into certain types of specialised cells. These are mostly used in autologous transplantations, where the patient’s own cells are used for treatment. One of the potential uses, which is now being tested, is in bone regeneration.
Another possibility, which also avoids potential adverse reactions of the immune system, are cells called induced pluripotent stem cells. These stem cells have essentially the same properties as embryonic stem cells but are generated from cells that are already specialised via a process called reprogramming. However, the safety and efficacy of these cells for treatment is also still being tested.