ACSP Position Statement: Mesenchymal Stem Cell Therapies in Sport and Exercise
Purpose and Scope
This Position Statement aims to provide appropriate guidelines for the use of mesenchymal stem cell (MSC) therapies in musculoskeletal conditions.
The purpose of the statement is to ensure that:
- The use of mesenchymal stem cell therapies is evidence-based;
- The patient/athlete’s health and welfare is a priority;
- The World Anti-Doping Authority guidelines are not breached;
This is a Position Statement and not an enforceable Code of Conduct. Therefore, it is intended as a guide as to what the ACSP considers is the current best clinical practice with regard to the use of MSCs for musculoskeletal conditions. The primary duty of care for all medical practitioners is to act in the best interest of the patient.
This Position Statement is intended for use by medical practitioners, sporting organisations, athletes and the general community.
There are many different types of stem cell but by definition all stem cells possess two distinct properties: firstly the ability to self-replicate (proliferate), and secondly the ability to differentiate in to more than one mature tissue type. This ACSP Position Statement only applies to MSCs and it does not refer to embryonic, hematopoietic or induced pluripotent (IPS) stem cells; or cellular therapies such as autologous tenocytes, autologous chondrocytes and platelet therapies.
Stem cells can be manufactured and returned to the donor (termed ‘autologous’ stem cells), or can be administered to a non-tissue matched recipient (termed ‘allogeneic’ stem cells).
MSCs are a very rare cell found in all human tissues. In order to generate high numbers of MSCs, typically, three processes are required. The MSCs are harvested (e.g. from bone marrow or adipose tissue), isolated, and then proliferated. This expansion process takes several weeks and is costly and is highly regulated. The resulting manufactured cells are also called mesenchymal stromal cells or mesenchymal progenitor cells. However, there are new manufacturing techniques that only involve the harvesting process and produce a non-expanded mixed cell population. This technique has the benefit of reduced cost and short preparation times (often less than 2 hours), but MSCs numbers are low, and the preparations contain a mixture of many cell types, therefore raising questions about whether these techniques are effective.
MSCs secrete a number of growth factors and cytokines that have been shown to be trophic (encourage tissue growth), chemotactic (attract other cells) and immunosuppressive (down regulate the immune and inflammatory systems). Experimental studies in animals show that MSCs have the potential to regenerate (rebuild) tissues of the musculoskeletal system. This tissue regeneration differs from current treatments that have the aim of tissue repair, which often involves scar tissue formation. Therefore, MSCs can potentially regenerate tissues that have been permanently damaged by repetitive overuse and/or age related degeneration. MSCs can be pre-differentiated (programmed) so that they form a specific tissue, and this property could theoretically be used to enhance the tissues of the body.
At present, no MSC therapies for musculoskeletal conditions have completed the initial three investigational phases of the four-phase clinical trials process. This means that either the safety or the efficacy of MSCs (or both) cannot be proven. Therefore, these therapies are still under investigation.
Phase I: Researchers test the safety and assess adverse effects of an intervention in a small group of people.
Phase II: The intervention is administered to a larger group to assess efficacy and to further evaluate safety.
Phase III: The treatment is given to large groups to confirm it’s effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the treatment to be used safely.
Phase IV: Post market surveillance is undertaken (after the introduction of the therapy to clinical practice) to assess any adverse effects associated with long-term use.
Typically, these therapies are marketed to athletes and active individuals, as a treatment for musculoskeletal conditions including osteoarthritis and tendinopathy.
Efficacy: No proven efficacy, therefore patients may be undertaking risks associated with treatment (injections etc.) for little or no benefit.
Safety: No proven safety, unanticipated harms could arise from the treatment.
Exploitation: Athletes and members of the public are often eager to find a solution to their musculoskeletal problems, for this reason they be keen to undertake therapies that are unproven. This can create an environment where exploitation can occur.
Stem Cell Tourism: There are no international standards or regulations that apply to the clinical use of stem cells, and countries will differ in what they will offer or accept.. Some countries permit medical practitioners to administer non-expanded autologous MSCs, whilst others permit the clinical use of expanded and allogeneic MSCs outside of clinical trials. This means that there is increasing ‘stem cell tourism’ by those seeking stem cell treatments. These practices are prone to exploitation of patients, and maybe associated with significant risks due to harm from unregulated and unproven therapies.
- MSC therapies are still under investigation, and should only be administered as part of a registered clinical trial.
- Despite early promise with MSC therapies, there is currently insufficient evidence from high quality clinical trials to recommend the clinical use of MSC therapies to regenerate joint or tendon.
- There is no evidence to support the systemic use of MSCs for localised musculoskeletal disease. However, systemic administration does increase the potential risks from MSC therapy.
- There is no quality evidence from independent that the addition of platelet rich plasma to stem cell treatments activates the MSCs.
- The ACSP does not endorse ‘Stem Cell Tourism’, whereby athletes/patients seek practitioners who promote MSC therapies outside a regulated medical environment.
- There is currently no evidence to support the clinical use of non-expanded MSC therapies, due to the low number of MSCs manufactured and likely sub-therapeutic dose.
- The ACSP does not support the use of MSCs for the purpose of performance enhancement. This is in direct breach of the WADA guidelines. However, the therapeutic use of (non- genetically modified) cell therapies is permitted under the WADA guidelines.
- In the future, if MSC therapies are proven to be safe and efficacious, the local use of MSCs in degenerate musculoskeletal disease is within the scope of practice of specialist ACSP Sports Physicians.
- The ACSP encourages the use of evidence-based treatments in both osteoarthritis and tendinopathy. These treatments include prescribed exercises, weight loss, some (non stem cell) injection therapies, simple analgesics, lifestyle changes and certain surgical treatments.
- In the development of any innovative therapy, the ACSP expects that appropriate research is undertaken prior to widespread application. Patient and athlete welfare should remain paramount. The ACSP does not endorse exploitation of the patient.