Projects / Programmes
Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| Code |
Science |
Field |
| B580 |
Biomedical sciences |
Skeleton, muscle system, rheumatology locomotion |
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
Mesenchymal stem cells, degenerative joint disorders, osteoarthritis, aging, regenerative medicine, tissue regeneration.
Researchers (19)
Organisations (3)
Abstract
The prevalence of degenerative disorders of the musculoskeletal tissues, in particular our joints, increases with age. Degenerative disorders such as osteoarthritis, affect normal function of the joints hence impair independent mobility in affected individuals. Pain is the main symptom of osteoarthritis and can have a devastating impact on people’s lives. According to the most recent report, that is 2018 UK Arthritis research report, an estimated 8.75 million people aged 45 years and over (33%) in the UK have sought treatment for osteoarthritis, and one-third of these patients have to retire early, give up work or reduce hours because of their condition. Pathophysiology of the osteoarthritis has been researched intensively, however no concrete targets to prevent or revert the cause of this disorder, have yet been identified. Osteoarthritis results from a combination of the breakdown of the joint and the body’s attempted endogenous regenerative process that seem to be impaired in osteoarthritis. In young and healthy individuals the regenerative process following tissue injury is successfully carried out by mesenchymal stem/ stromal cells (MSCs). These progenitor cells build up our tissues during embryonic development. In adult organisms they are retained as rare populations within several tissues (i.e. bone marrow, adipose tissue, muscles, synovium, cartilage, tendons etc.) showing the ability to regenerate damaged tissues such as broken bone or torn muscle. These stem cells could be best described as the “keepers” of the tissue endogenous regenerative capacity. The majority of the evidence on their regenerative capacity comes from high impact basic studies. In these studies sophisticated transgenic animal models are used that can trace MSCs, either from their embryonic development throughout adult life, or in health and disease. We have recently identified a novel MSC population in adult synovium that can regenerate cartilage following joint injury, and even reform new joints. These break-through basic studies provide evidence that each adult individual harbours an endogenous repair kit within their tissues that comes in the form of MSCs. The question is - are we able to identify these cells in humans and stimulate them to redo the excellent work they have done during our embryonic tissue formation? To approach the ultimate goal of stimulating endogenous regenerative capacity to treat degenerative disorders, the proposed project aims to elucidate the features MSCs, the “keepers” of our endogenous regenerative capacity within human joints. Stem cell exhaustion and hence decrease of the tissue endogenous regenerative capacity have been recognized as one of the several hallmarks of aging. To tackle the exhaustion of MSCs, the inevitable prerequisite is to first gain a better knowledge on human MSCs in health and disease. If we knew, how these cells are affected in certain degenerative disorders such as osteoarthritis, we could help them to regain their regenerative capacities and stimulate them to heal the damage tissues.
We will investigate and compare MSCs derived from different joint tissues such as bone, muscle and synovium in various stages of osteoarthritis and healthy controls. Our hypothesis is that MSCs in osteoarthritis are exhausted or impaired, thus not being able to prevent the progression of degenerative disorders. By identifying and understanding the features of MSCs in degenerative disorders more fully, it puts us in a better position down the line to be able to target them with drugs or other treatments. Ideally we want to be able to get to a stage where we can give exhausted cells that are losing their function, a boost. The results of this project will pave the way to develop novel approaches in regenerative medicine to tackle joint degeneration and osteoarthritis at early stages and prevent high morbidity and medical costs associated with late-life disease.
Significance for science
The results of the proposed project will contribute to further development of regenerative medicine. Regenerative medicine is currently the most ambitious branch of modern medicine, as it seeks to restore degenerated tissues due to age or other causes. The main tools of regenerative medicine are mesenchymal stem/ stromal cells (MSCs) that are found within various connective tissues in adult organisms where they still possess regenerative abilities. Moreover, they are even able to form new joints. This was demonstrated in a recent study where PI of the proposed project was one of the main investigators. Although we are still far from being able to form new human joints in laboratory conditions, we can stimulate the endogenous regenerative potential, that is, within the individual patient. In order to achieve this goal, we must first establish how MSCs are exhausted in degenerative disorders. Millions of people globally are suffering from degenerative joint disorders, in particular osteoarthritis. This debilitating disorder also presents tremendous socioeconomic burden. The main obstacle to solving this global challenge is the lack of an effective causative treatment, since the cause of osteoarthritis is still unknown. Most of the studies in the field of MSCs are strictly separated into basic or clinical studies. The findings on the regenerative ability of MSCs discovered in basic studies are hence not translated into clinical practice where these cells could be exploited to regenerate human joints. In the proposed project, both basic and clinical researchers will join their forces with the aim of identifying MSCs that are the carriers of the tissue endogenous regeneration capacity. The only question is can we identify these MSCs and take advantage of them in order to improve the treatment of degenerative joint disorders, thus helping to solve the problems of an aging modern society?
The discoveries gained during this project will be published in scientific journals in the field of orthopaedics, regenerative medicine and cell therapy, and presented at international conferences. During this project cell and tissue bio bank will be created including several well-characterized tissues and MSCs. This bio bank will serve as a good starting point for new projects or collaborations in international projects, where these cells could be modified in order to stimulate their endogenous regenerative potential. The PI of the proposed project is still in contact with colleagues from the Institute of Medical Sciences in Aberdeen, where they would like to determine the joint morphogenetic ability of these MSCs to identify the mechanisms of these cells and reactivate them for the needs of regenerative medicine. The PI of the proposed project is also collaborating with Ludwig Boltzmann Institute at Austrian Cluster for Tissue Regeneration, where they are particularly interested in these MSCs to test their innovative ways of promoting their regenerative properties.
Significance for the country
The results of the proposed project will contribute to further development of regenerative medicine. Regenerative medicine is currently the most ambitious branch of modern medicine, as it seeks to restore degenerated tissues due to age or other causes. The main tools of regenerative medicine are mesenchymal stem/ stromal cells (MSCs) that are found within various connective tissues in adult organisms where they still possess regenerative abilities. Moreover, they are even able to form new joints. This was demonstrated in a recent study where PI of the proposed project was one of the main investigators. Although we are still far from being able to form new human joints in laboratory conditions, we can stimulate the endogenous regenerative potential, that is, within the individual patient. In order to achieve this goal, we must first establish how MSCs are exhausted in degenerative disorders. Millions of people globally are suffering from degenerative joint disorders, in particular osteoarthritis. This debilitating disorder also presents tremendous socioeconomic burden. The main obstacle to solving this global challenge is the lack of an effective causative treatment, since the cause of osteoarthritis is still unknown. Most of the studies in the field of MSCs are strictly separated into basic or clinical studies. The findings on the regenerative ability of MSCs discovered in basic studies are hence not translated into clinical practice where these cells could be exploited to regenerate human joints. In the proposed project, both basic and clinical researchers will join their forces with the aim of identifying MSCs that are the carriers of the tissue endogenous regeneration capacity. The only question is can we identify these MSCs and take advantage of them in order to improve the treatment of degenerative joint disorders, thus helping to solve the problems of an aging modern society?
The discoveries gained during this project will be published in scientific journals in the field of orthopaedics, regenerative medicine and cell therapy, and presented at international conferences. During this project cell and tissue bio bank will be created including several well-characterized tissues and MSCs. This bio bank will serve as a good starting point for new projects or collaborations in international projects, where these cells could be modified in order to stimulate their endogenous regenerative potential. The PI of the proposed project is still in contact with colleagues from the Institute of Medical Sciences in Aberdeen, where they would like to determine the joint morphogenetic ability of these MSCs to identify the mechanisms of these cells and reactivate them for the needs of regenerative medicine. The PI of the proposed project is also collaborating with Ludwig Boltzmann Institute at Austrian Cluster for Tissue Regeneration, where they are particularly interested in these MSCs to test their innovative ways of promoting their regenerative properties.
Most important scientific results
Interim report
Most important socioeconomically and culturally relevant results
