About developmental biology, regenerative, reproductive and reparative medicine
The speciality called developmental biology includes the study of how genes regulate cell growth, the differentiation of cells from the stem cell stage and onwards, and the processes that result in the formation of tissues and organs. This knowledge in turn forms the basis of advancements in reproductive medicine as well as reparative medicine, and may result in completely new principles of treatment.
Researchers investigate how genes, cells, tissues, organs and synthetic biomaterials, singly or in co-operation, may be used to repair, replace and strengthen failing biological functions or damage to the human body. New tissues can even be used to develop new pharmaceuticals.
Regenerative medicine and stem cell research are two rapidly growing fields in which revolutionary scientific progress has been made in recent years. There is great optimism within the medical profession regarding the use of this knowledge to cure disease. Regenerative medicine aims to replace lost or damaged tissue with new cells derived from stem cells that have been cultivated in the laboratory, or with the patients own stem cells, which have been activated directly to develop into the required cell type.
This kind of technology has been used for a long time in transplantation of bone marrow for the treatment of leukaemia and anaemic disorders, and for the regeneration of skin after burn trauma. There is, however, good reason to believe that regenerative medicine will, in the future, come to play an increasingly important role in a number of other medical specialities where today there is no satisfactory therapeutic approach. Examples of these are: neuro-degenerative disorders such as Parkinson's disease, diabetes, spinal cord damage and myocardial infarction.
Stem cell research
Stem cells are immature cells that have the potential to develop into different types of new mature cells. Specialised research into stem cells performed at KaroIinska Institutet aims to discover new treatments for spinal cord injuries, Parkinson's disease, Alzheimer's disease, heart failure and damage to bone and cartilage, to give some examples. KI conducts world-class research into embryonic stem cell lines, stem cell lines from adults and iPS-cells. A simple way to explain the concept of iPS cells is that they are manufactured stem cells. The method of how to rewind the cell development back to the stem cell stage was awarded the Nobel Prize in Medicine or Physiology in 2012.
Basic research into stem cells aims to discover and understand exactly what happens when a stem cell develops into a more specialised cell, such as a nerve cell or glial cell. One line of research attempts to identify all the signals that regulate the early development of the normal cell and then develop strategies to stimulate cellular regeneration.
Researchers at KI have achieved early successes in the study of stem cells in the brain and nervous tissue of humans. One example is the manipulation of stem cells to become dopamine producing cells in culture (cultured cells are cells grown outside the body). These are now being investigated in animal models, and this is an important first step towards, sometime in the future, being able to replace the dopamine cells that are lost during the development of Parkinsons disease.
Research is also conducted at KI into haematopoietic stem cells (give rise to blood cells) and mesenchymal stem cells (from the early development of the embryo). These can develop into a number of different cells in bone tissue, cartilage, muscle, tendon and adipose tissue. Potential future applications for such cells are the treatment of leukaemia, bone fractures that fail to heal and damage or deformities of the facial bones.
Other experiments attempt to use stem cells to repair damaged cells in the heart after an infarction, auditory stem cells to repair impaired hearing, and the repair of the traumatised spinal cord using oligodendrocytes, a class of nerve cells.
Stem cells in brief
Stem cells are the source of all cells in the body. Here are the three types researchers use.
Embryonic stem cells
Source: The immature embryo.
Advantage: Great potential, can form almost all types of cells in the body (pluripotency).
Disadvantage: Hard to access, must be extracted from an embryo the first week after the ovum is fertilised. It is also ethically controversial.
Mature stem cells
Source: Body tissue from both children and adults.
Advantage: Relatively easy to access.
Disadvantage: Can only be developed into certain cells in certain tissue (multipotency).
Example: Mesenchymal stem cells that can develop bones, cartilage and fat.
Source: Common skin cells that are reprogrammed to become stem cells in a laboratory.
Advantage: Unlimited access. Researchers can tailor-make stem cells for research. Pluripotent.
Disadvantage: Still a risk factor of using them in treatments, may have undesirable qualities.
Text: Fredrik Hedlund, first published in Swedish in the magazine Medicinsk Vetenskap, no 4, 2015.
Transplantation of cells, organs and bone marrow
Transplantation research and the improvement of transplantation techniques are continually being carried out at KI. Today it is possible to transplant an organ even if the tissue types are not identical.
A possible treatment for patients with liver failure and children with congenital diseases could be to transplant a liver in combination with stem cells, or to transplant liver cells. Research into the transplantation of insulin-producing islet cells from the pancreas is another area of intensive research.
Stem cell transplantation, previously called bone marrow transplantation, is another research speciality at KI. This involves the exchange of the patients diseased bone marrow with healthy bone marrow from a donor, for example, in the treatment of leukaemia. Part of this research is concerned with improving the life expectancy after transplantation by the prevention of infections and by preventing the new bone marrow from attacking its host.
From egg and sperm to an adult Human
Research into reproduction comprises basic clinical and epidemiological investigations into normal and pathological processes from egg and sperm cells to the adult individual. This includes research into pregnancy, birth, the newborn infant, the interplay between parents and children and the short- and long-term health of women and men.
This area of research brings together many medical specialities such as gynaecology, paediatrics, psychology, psychiatry, neurology and clinical genetics.
General gynaecology is concerned with research into the female genital region, including hormones, disease and deformities.
Areas of research include for example menstrual dysfunction and its causes, polycystic ovary syndrome (PCOS), stress-related incontinence, menopause and vulvar vestibulitis. It also encompasses basal hormonal and genetic connections between metabolism and reproduction, as well as inadequate ovarian function and disorders of sex development.
The effect of hysterectomy (removal of the uterus) is also a research focus, as is research into hereditary aspects of the dysfunction of the lower urinary tract and pelvic floor and risk factors for cancer in the urinary tract and the kidneys.
Germ cells, fertility and infertility
Reproductive research at KI comprises basic biomedical research on germ cells and fertilisation as well as research on infertility and in-vitro fertilisation, also called IVF or test-tube fertilisation (awarded the Nobel Prize in Physiology or Medicine in 2010).
Research is in progress into the function of the endometrium, the effect of hormones on the reproductive organs, and the development and differentiation of male and female germ cells. Researchers also examine the interplay between egg and sperm during fertilisation and the interplay between the embryo and the endometrium. Other research areas are contraception, and spontaneous and induced abortion.
There is a tradition of research into the causes and treatment of infertility, and methods of in vitro fertilisation are being developed to decrease the need for women to undergo hormonal treatment while still providing eggs of adequate quality. Attempts are being made to improve the cryopreservation of germ cells and ovarian tissue in advance of cancer treatment.
Pregnancy and childbirth
Pregnancy and childbirth encompass the effects of various factors on the ability to become pregnant, pregnancy itself and labour, as well as how mother and child are affected, from both short and long-term perspectives.
This area of research is concerned with the physiology of labour and the interaction between foetal growth, the possible risk of pre-eclampsia and the later risk of cardiovascular complications for the mother. Research also studies the ripening of the cervix in preparation for labour, labour pains, premature birth, induced labour, extended labour and caesarean section. Breast feeding and its associated difficulties are also on the research agenda.
A further subject of investigation is the issue of smoking during pregnancy, which increases the risk of complications for both the mother and her child.
Paediatric research is concerned with the development, physiology, diagnosis and therapy of the embryo and the newborn infant. Research concerning diseases of older children can be found under the respective speciality, for example oncology or endocrinology.
Foetal medicine studies, amongst other things, developmental retardation, deformities and diseases of the embryo and their prevention and treatment, for example, the prevention of kidney damage caused by malnutrition during intrauterine development. Studies are also carried out into the effects of smoking on the foetus, for example, growth retardation, foetal mortality, premature labour and sudden infant death syndrome (SIDS).
The development of transplantation techniques for the treatment of embryos that would otherwise not survive is an experimental area of research. Examples of this are the transplantation of stem cells to embryos with serious skeletal disease, or unusual immunological deficiency diseases and, in the future, hopefully also for embryos with heart conditions.
At KI, neonatological research, relating to the newborn infant, studies the stress reactions of birth, the newborn brain, pain in the newborn infant and the medical complications that arise as a result of premature birth.
Other research includes developmental disorders and deformities of the central nervous system of children, dermatitis, inherited defects of the immune system and leukaemia. There is also research into why premature babies are unable to empty all the amniotic fluid out of their lungs, the function of the fluid pathways in the kidneys and lungs, and congenital deformities of the kidneys, adrenal glands, urinary tract and intestines.
KI carries out research in odontology, which is the study of diseases of and damage to teeth, but also the oral cavity and adjacent tissues such as the masticatory muscles and the jaw joints.
At KI the possible relationship between periodontitis and cardiovascular conditions has been the subject of research for many years. Researchers are also investigating complications and diseases of the oral cavity in children with various chronic conditions or cancer, and their treatments. Other studies are focussed on the diagnosis and treatment of temporomandibular joint diseases and the mapping of inflammatory patterns in these diseases.
Reparative medicine – surgery and orthopaedics
Research in reparative medicine is centred on a number of surgical specialities with the goal of repairing, removing and/or replacing damaged organs and tissues that result from accidents or illness. KI researchers investigate disease processes, for examplein the musculoskeletal system, all the way from the cellular level to patient-oriented clinical research. Extensive research is carried out into osteoporosis, arthritis and other conditions of the joints, as well as the prevention and treatment of fractures. Damage to cartilage, tendons, ligaments and joint capsules are other fields of research. Orthopaedic implants and methods to preserve functionality after total hip replacement surgery are also studied.
Other areas of research include inguinal hernia, various cancers, abdominal wall surgery and acute abdominal pain. Laparascopy (keyhole surgery) and telemedicine, which reduce trauma for the patient when compared with open surgery, are also studied. Other areas of research include post-operative nausea and vomiting, advanced post-operative analgesia and targeted circulatory support during operations on older patients.
In recent years, certain aspects of regenerative medicine are also included in the concept of reparative medicine.