Stem cell research is often in the news; whether it's claims of new therapies or controversies about the types of cells used. What is the true potential of stem cells behind the headlines? How valuable are they as tools for research and therapy? And what are the advantages and limitations of different types of stem cells for different uses?
The average age of your cells may be as low as 10 years - even if you're middle-aged; stem cells are at work replacing old cells with new in many parts of your body.
Mouse embryonic stem cells with yellow marking Oct4 - a protein that is essential to keep them undifferentiated
Mouse skin; skin is made up of several layers and contains more than one type of skin stem cell; the arrows show where stem cells are found
Dendrites, the complex extensions formed by nerve cells to receive and transfer electrical signals; the nerve cells were generated from iPSCs
Not all stem cells come from an early embryo. In fact, we have stem cells in our bodies all our lives. One way to think about stem cells is to divide them into three categories:
You can read in detail about the properties of these different types of stem cells and current research work in our other fact sheets. Here, we compare the progress made towards therapies for patients using different stem cell types, and the challenges or limitations that still need to be addressed.
Embryonic stem cells (ESCs) cells have unlimited potential to produce specialised cells of the body, which suggests enormous possibilities for disease research and for providing new therapies. Human ESCs were first grown in the lab in 1998. Recently, human ESCs that meet the strict quality requirements for use in patients have been produced. These ‘clinical grade’ human ESCs have been approved for use in a very small number of early clinical trials. One example is a clinical trial carried out by The London Project to Cure Blindness, using ESCs to produce a particular type of eye cell for treatment of patients with age-related macular degeneration. The biotechnology company ACT is also using human ESCs to make cells for patients with an eye disease: Stargardt’s macular dystrophy.
Current challenges facing ESC research include ethical considerations and the need to ensure that ESCs fully differentiate into the required specialised cells before transplantation into patients. If the initial clinical trials are successful in terms of safety and patient benefit, ESC research may soon begin to deliver its first clinical applications.
Many tissues in the human body are maintained and repaired throughout life by stem cells. These tissue stem cells are very different from embryonic stem cells.
Blood and skin stem cells: therapy pioneers
Stem cell therapy has been in routine use since the 1970s! Bone marrow transplants are able to replace a patient’s diseased blood system for life, thanks to the properties of blood stem cells. Many thousands of patients benefit from this kind of treatment every year, although some do suffer from complications: the donor’s immune cells sometimes attack the patient’s tissues (graft-versus-host disease or GVHD) and there is a risk of infection during the treatment because the patient’s own bone marrow cells must be killed with chemotherapy before the transplant can take place.
Skin stem cells have been used since the 1980s to grow sheets of new skin in the lab for severe burn patients. However, the new skin has no hair follicles, sweat glands or sebaceous (oil) glands, so the technique is far from perfect and further research is needed to improve it. Currently, the technique is mainly used to save the lives of patients who have third degree burns over very large areas of their bodies and is only carried out in a few clinical centres.
Cord blood stem cells
Cord blood stem cells can be harvested from the umbilical cord of a baby after birth. The cells can be frozen (‘cryopreserved’) in cell banks and are currently used to treat children with cancerous blood disorders such as leukaemia, as well as genetic blood diseases like Fanconi anaemia. Treatment of adults has so far been more challenging but adults have been successfully treated with double cord transplants. The most commonly held view is that success in adults is restricted by the number of cells that can be obtained from one umbilical cord, but immune response may also play a role.One advantage of cord blood transplants is that they appear to be less likely than conventional bone marrow transplants to be rejected by the immune system, or to result in a reaction such as Graft versus Host Disease. Nevertheless, cord blood must still be matched to the patient to be successful.
There are limitations to the types of disease that can be treated: cord blood stem cells can only be used to make new blood cells for blood disease therapies. Although some studies have suggested cord blood may contain stem cells that can produce other types of specialised cells not related to the blood, none of this research has yet been widely reproduced and confirmed. No therapies for non-blood-related diseases have yet been developed using blood stem cells from either cord blood or the adult bone marrow.
Mesenchymal stem cells
Mesenchymal stem cells (MSCs) are found in the bone marrow and are responsible for bone and cartilage repair. They also produce fat cells. Early research suggested that MSCs could differentiate into many other types of cells but it is now clear that this is not the case. MSCs, like all tissue stem cells, are not pluripotent but multipotent – they can make a limited number of types of cells, but NOT all types of cells of the body. Claims have also been made that MSCs can be obtained from a wide variety of tissues in addition to bone marrow. These claims have not been confirmed and scientists are still debating the exact nature of cells obtained from these other tissues.
No treatments using mesenchymal stem cells are yet proven. Some clinical trials are investigating the safety and effectiveness of MSC treatments for repairing bone or cartilage. Other trials are investigating whether MSCs might help repair blood vessel damage linked to heart attacks or diseases such as critical limb ischaemia, but it is not yet clear whether these treatments will be effective. MSCs do not themselves produce blood vessel cells but might support other cells to repair damage. Indeed MSCs appear to play a crucial role in supporting blood stem cells.
Several claims have been made that MSCs can avoid detection by the immune system and that MSCs taken from one person can be transplanted into another with little or no risk of rejection by the body. The results of other studies have not supported these claims. It has also been suggested that MSCs may be able to affect immune responses in the body to reduce inflammation and help treat transplant rejection or autoimmune diseases. Again, this has yet to be conclusively proven but is an area of ongoing investigation.
Stem cells in the eye
Clinical studies in patients have shown that tissue stem cells taken from an area of the eye called the limbus can be used to repair damage to the cornea – the transparent layer at the front of the eye. If the cornea is severely damaged, for example by a chemical burn, limbal stem cells can be taken from the patient, multiplied in the lab and transplanted back onto the patient’s damaged eye(s) to restore sight. However, this can only help patients who have some undamaged limbal stem cells remaining in one of their eyes. The treatment has been shown to be safe and effective in early stage trials. Further studies with larger numbers of patients must now be carried out before this therapy can be approved by regulatory authorities for widespread use in Europe.
A relatively recent breakthrough in stem cell research is the discovery that specialised adult cells can be ‘reprogrammed’ into cells that behave like embryonic stem cells, termed induced pluripotent stem cells (iPSCs). The generation of iPSCs has huge implications for disease research and drug development. For example, researchers have generated brain cells from iPSCs made from skin samples belonging to patients with neurological disorders such as Down’s syndrome or Parkinson’s disease. These lab-grown brain cells show signs of the patients’ diseases. This has implications for understanding how the diseases actually happen – researchers can watch the process in a dish – and for searching for and testing new drugs. Such studies give a taste of the wide range of disease research being carried out around the world using iPSCs.
The discovery of iPSCs also raised hopes that cells could be made from a patient’s own skin in order to treat their disease, avoiding the risk of immune rejection. However, use of iPSCs in cell therapy is theoretical at the moment. The technology is very new and the reprogramming process is not yet well understood. Scientists need to find ways to produce iPSCs safely. Current techniques involve genetic modification, which can sometimes result in the cells forming tumours. The cells must also be shown to completely and reproducibly differentiate into the required types of specialised cells to meet standards suitable for use in patients.
Stem cells are important tools for disease research and offer great potential for use in the clinic. Some adult stem cell sources are currently used for therapy, although they have limitations. The first clinical trials using cells made from embryonic stem cells are just beginning. Meanwhile, induced pluripotent stem cells are already of great use in research, but a lot of work is needed before they can be considered for use in the clinic. An additional avenue of current research is transdifferentiation – converting one type of specialised cell directly into another.
All these different research approaches are important if stem cell research is to achieve its potential for delivering therapies for many debilitating diseases. The table below gives a brief overview of the different types of stem cells and their uses. You can also download this table as a pdf.
EuroStemCell information on clinical trials and stem cell treatment
EuroStemCell fact sheets on stem cell types and research areas
EuroStemCell information on cord blood and the diseases it is used to treat
International Society for Stem Cell Research website for patients about stem cell treatments
Cell replacement therapies: iPS technology or transdifferentiation? Article by Thomas Graf