The right kind of transplant could restore some functions of the body and make everyday life easier.
Brain tissue is one of the most complicated in the human body, which is why it has been very difficult to find efficient treatments for spinal cord injuries (SCIs). However, stem cells are now offering new hope in the treatment of such injuries.
Researchers at BioMediTech at the University of Tampere are investigating SCIs in ways that could definitively improve the quality of life of SCI patients. Postdoctoral Researcher Laura Ylä Outinen is working on a three-year Academy of Finland-funded project to develop a three dimensional stem cell model, which will be used to investigate the function of the spinal cord. The main goal is to develop a model utilising the technological development of cell transplants in the treatment of SCI patients.
“The transplant would improve the functions of the spinal cord in ways that could restore some functional ability, for example the movement of limbs,” Ylä-Outinen says.
The transplant would cure some of the existing damage and prevent the development of new damage.
The research is being conducted in close cooperation with clinicians, such as neurologists. Clinical practitioners are able to tell where the real problems lie and can thus help develop the research in the right directions. For example, wrist and hand mobility could be more significant for the everyday life of an SCI patient than being able to stand up out of the wheelchair.
“We often think that the main goal in the treatment of SCI is to get the patients up from the wheelchair. That is naturally a big thing, but spinal cord injuries also involve many other symptoms, such as urinary incontinence, that diminish the quality of life and whose treatment is very important for the patient,” Ylä-Outinen explains.
The aim of using transplants is thus not necessarily to heal the patient completely but to restore functional ability in order to make the patient’s everyday life run more smoothly and improve his or her quality of life.
Treatments for spinal cord injuries are being researched and developed globally. Group leader Susanna Narkilahti from BioMediTech’s Neuro Group estimates that around ten clinical trials of cell transplant therapies are currently ongoing in the world. The trials are still in their initial stages, during which the safety of using transplants is being investigated. As yet, no treatment or product is ready.
“Thus far, it seems that cell transplants have not been harmful to patients. However, at this stage we are only talking about a few years of follow-up times, and in these stem cell-based treatments the follow-up times must be longer.”
The SCI model that Ylä-Outinen is developing is different from the other transplants being tested. In addition to neurons, the model also includes a hydrogel matrix that is used to create a three dimensional environment, making the model better at mimicking a real spinal cord.
The hydrogel matrix is also thought to support the survival of the transplanted cells in the human body. Ylä-Outinen’s aim is to make the model so accurate that it could be used as the basis for developing a viable transplant for transplantation therapies.
“Hydrogel matrices are the next or even the third generation of transplant technologies. They show the direction in which the transplant technologies are currently developing,” Narkilahti explains.
The development of stem cell technologies has made disease modelling popular. The patient’s own cells can be used to make a laboratory model of his or her disease. This is hopefully a step towards personalised medicine, since it offers an opportunity to investigate the behaviour of each patient’s illness and to analyse which therapy would be the most efficient.
Disease models are also being used by pharmaceutical companies to analyse the toxicological effects of drug compounds.
BioMediTech’s Neuro Group is conducting research on neurons and glial cells, which are being developed from human pluripotent stem cells in the laboratory. The Neuro Group has mainly researched in vitro models for the research and treatment of SCI, multiple sclerosis and epilepsy. The research projects are carried out in close cooperation with research groups at Tampere University of Technology.
It is often hard to predict the prognosis of neurological diseases. For example, epilepsy has hundreds of variants, and even though multiple sclerosis can be divided into four categories, no illness completely behaves in a way that can be predicted on the basis of its category. Similarly, the origin and progress of SCI cases are always totally unique.
“Obviously, patients cannot be offered efficient treatments because we do not sufficiently understand the mechanisms of these diseases,” Narkilahti says.
“That is why we are so interested in developing personalised diagnoses and treatments.”
Time is a challenge related to the introduction of personalised disease models. How quickly can the cells used to study the disease be produced?
“At present, the time scales are too long to enable an early diagnosis. However, stem cell techniques and technologies are developing fast, which is also making the disease modelling faster,” Narkilahti explains.
“Speed is needed, for example, when the disease model is used to choose the right medication for the patient. Currently, we cannot get such results the following week. This is a global challenge in disease modelling.”
Stem cell technologies have taken great steps forward in recent years; however, research takes time. The time it takes to apply an invention to clinical practice is unavoidably long. In spite of this, such development work is highly motivating.
“All of us researchers think that this work is really necessary. It is interesting and at times very challenging,” Narkilahti says.
“We are dealing with the most complicated tissue in the human body. Thus, studying brain tissue is not so straightforward. A lot of patience is required.”
Text: Tiina Lankinen
Photographs: Jonne Renvall
Research is opening up new opportunities for MS therapies
Multiple sclerosis (MS) is the most common disease of the central nervous system affecting the mobility and functional ability of young adults. However, its mechanisms are not fully understood: it is presumed that the disease is caused by a combination of genetic and environmental factors. The disease occurs more frequently in some regions in Finland than in others, and more women suffer from it than men.
MS causes the patient’s immune system to attack the body’s myelin, which covers and protects the neurons. Myelin is an insulator that facilitates the transmission of electric impulses between the brain and other parts of the body. This is why MS patients experience various symptoms related to sensation, vision or mobility.
Researchers at the University of Tampere’s BioMediTech are using stem cells as tools to develop a myelination model that would enable the close inspection of myelination.
The aim is to use the model to study the formation of the myelin sheath around neurons and to determine what happens when the myelin is damaged. This will enable researchers to gain a better understanding of the mechanisms of the disease and develop new therapies not only for MS but also for other demyelinating diseases.
A patent is pending for this unique model, and Postdoctoral Researcher Mervi Ristola just received three years funding from the Academy of Finland for the project.
“In the model, we could cause damage to the myelin sheath with various drugs and restore its function again. This would enable the examination of the disease mechanisms and the medicines that could cure the damage,” Ristola says.
The MS therapies currently used suppress the immunological reaction. The new cellular model could open up opportunities for the development of new kinds of therapies that aim to create new myelin in the brain. The medication currently available does not have this effect.
The cellular model combines human neurons with oligodendrocytes that produce myelin in the brain. They are placed in a structure made of silicon, and the interaction between the neurons and oligodendrocytes is then investigated by imaging techniques and electrophysiological measurements.
When the model is complete, it will be shared widely.
“The aim is to make the model available to other research groups and the pharmaceutical industry,” Ristola says.
Stem cell research at the University of Tampere:
BioMediTech is a joint institute of the University of Tampere and Tampere University of Technology. A part of BioMediTech is a School of the University of Tampere educating Master’s degree and doctoral students in biomedicine and biotechnology.
The institute is conducting advanced research on stem cells. Four research groups are working in the field of stem cells and tissue engineering. For example, the stem cell research on eye diseases is quite advanced. Associate Professor Heli Skottman and her research group have been able to differentiate stem cells that can be used to heal retinal deficits, and a stem cell-based therapy is being developed.
Text: Tiina Lankinen
Photographs: Jonne Renvall