What’s the problem?
Osteoarthritis (OA) is a painful, degenerative disease of the joints, frequently impacting hips, knees, neck, lower back and hands. Ageing, injury and wear and tear can deplete the cartilage tissue that is essential for normal joint function. This can result in inflammation, loss of mobility and severe pain. Often, painful bone spurs (osteophytes) may develop. OA sufferers can experience significant disability, loss of income and reduced quality of life.
An analysis of Global Burden of Disease (GBD) by the World Health Organisation estimated that in 2013, 242 million people were living with OA of the hip and/or knee. The number of adults with clinically diagnosed OA is expected to increase by 29% from 2012 to 2022 with obesity and ageing populations contributing to this trend[1]. OA is predicted to become the 4th leading cause of disability worldwide in 2020[2][3].
Treatment options for OA generally address the symptoms rather than the disease and include pain management, intra-articular injections and joint replacement surgery. A significant proportion of people with OA do not benefit fully from joint replacement surgery. Surgical intervention also carries associated risks and expenses. Non-surgical options can involve long-term use of non-steroidal anti-inflammatory drugs and the use of opioids in pain management. While some people manage to live well with OA, for many there is a real need to develop new therapeutic alternatives.
Regenerative cell therapies show potential for the treatment of chronic and degenerative diseases, such as OA. However, we need to understand more about how cell-based treatments work and to generate more scientific data in support of new approaches. In addition, therapeutic cells and cell products can be complicated to source and production is costly and labour intensive, with variable results. We need to establish sustainable sources of therapeutic cells and reliable, cost-effective means of production at scale and in line with regulatory requirements for therapeutic use.
What’s the solution?
In AutoCRAT we will explore new cell and cell-based/guided therapies for OA. We will:
- Generate novel, sustainable, therapeutic cells.
- Explore the secreted factors produced by therapeutic cells and their effect.
- Test the cell therapies discovered in vivo.
AutoCRAT will identify next-generation therapies for OA and cartilage repair and will enable economic, sustainable and regulatory-compliant means of production of cell and cell products for therapeutic use.
We aim to deliver new therapies (i) for cartilage repair and (ii) for the prevention of OA and treatment of the disease. Our work will explore the use of cartilage cells (chondrocytes) to repair cartilage tissue. We will use mesenchymal stromal cellsPlastic-adherent cells that can be isolated from bone marrow, adipose, and other tissue sources. These cells have the capacity to differentiate into bone cells, cartilage cells, muscle cells and fat cells. Studies have shown MSC may have therapeutic effects through their secretome. (MSCsPlastic-adherent cells that can be isolated from bone marrow, adipose, and other tissue sources. These cells have the capacity to differentiate into bone cells, cartilage cells, muscle cells and fat cells. Studies have shown MSC may have therapeutic effects through their secretome.), which have shown potential therapeutic effects in other studies[4], to prevent development of or to treat established OA. We will also explore the therapeutic effects of the particles secreted by MSCsPlastic-adherent cells that can be isolated from bone marrow, adipose, and other tissue sources. These cells have the capacity to differentiate into bone cells, cartilage cells, muscle cells and fat cells. Studies have shown MSC may have therapeutic effects through their secretome. known as extracellular vesiclesExtracellular Vesicles or EVs are sub-cellular packages released by MSC. EV have shown potential to deliver therapeutic effects., or EVsExtracellular Vesicles or EVs are sub-cellular packages released by MSC. EV have shown potential to deliver therapeutic effects..
As part of our work we will generate economically sustainable and reproducible therapeutic cell sources. We will also develop a novel manufacturing platform for the new therapies that we select. This will be a closed, scalable and regulatory-compliant automated system for aseptic production of cells and cell products for therapeutic use.
AutoCRAT will build on the ground-breaking work carried out by project partners on the automated production of therapeutic cells in earlier projects such as StemCellFactory and AUTOSTEM and in the StemCellDiscovery initiative (fully automated laboratory available as a testbed for cooperating universities and companies).
The technologies developed in the Project will also be capable of producing cells and cell products for many other diseases and conditions in addition to OA.
The AutoCRAT approach to the challenges of treating OA
Who will benefit?
We will develop new regenerative therapies and production methods to address the unmet needs of people with OA. We also expect that our results will have application to other diseases and conditions.
Our work will also help increase the strength and depth of the research community and industry in the sector.
AutoCRAT therefor aims to benefit people with OA and their families, clinicians, health service providers, employers, industry, the wider scientific community and society as a whole.
Where can I find out more?
Find out more technical details about the Project on our AutoCRAT Science Page.
View and download our Project Materials here.
Press releases and contacts are on our Media Page.
Stay up to date on Project news here and contact us here.
Find more information about OA and OA patient organisations on the websites below:
[1] Pers, YM et al. Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial. Stem Cells Transl Med. 2016 Jul;5(7):847-56
[2] Woolf, AD et al. The bone and joint decade. Strategies to reduce the burden of disease: the Bone and Joint Monitor Project. J Rheumatol Suppl 2003, 67: 6–9
[3] Kingsbury SR et al. Osteoarthritis in Europe: impact on health status, work productivity and use of pharmacotherapies in five European
[4] https://www.frontiersin.org/articles/10.3389/fbioe.2019.00009/full