Research

Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system

Code:

J3-1749

Range:

01. July 2019 - 30. June 2023

Range:

0,42 FTE

Leader:

Janja Zupan

Field:

3.03 Medical sciences/ Neurobiology

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 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.