Ian McDermott on the issue of stem cell therapy and how some companies are wrongly claiming it as the new ‘cure-all’ for a wide range of ailments, including knee arthritis
Not a week goes by now without at least one or more of my patients asking in clinic: “Can’t you just inject some stem cells?”
Stem cell research has been around for many years, and the research is still very much ongoing. Techniques for deriving embryonic stem cells from early mouse embryos were first developed nearly 40 years ago, in 1981, and in 1998 researchers managed to derive stem cells from human embryos and grow them in a lab. Unfortunately, however, the term ‘stem cell’ has been hijacked by marketeers and salesmen, and the internet is now rife with certain clinics touting ‘stem cell therapy’ as the new cure-all for a whole disparate wide range of ailments, including knee arthritis.
The first major issue is ‘what is a stem cell?’. In basic terms, a pluripotent stem cell is a cell that has the ability to produce any of the specialised cells that make up specific tissues, such as brain tissue, muscle, bone, liver, etc. A mesenchymal stem cell (MSC) is a cell that has the ability to produce the cell types that are found specifically in musculoskeletal tissues such as bone, cartilage and ligaments. These cells are actually found relatively sparsely in the adult human, and accurately identifying them requires complex lab-based techniques. Likewise, getting MSCs to multiply and to differentiate correctly into the right specialised cell lines is extremely difficult. Getting MSCs to then grow or regenerate the correct specialised tissue structures and to repair or regenerate actual damaged anatomical structures is an enormous leap on from this.
Scientists are continuing their highly complex, highly specialised lab-based research into ‘stem cells’, with some encouraging initial results having been published for certain specific animal models. However, these studies are highly controlled, extremely specific and rigorous projects that use carefully lab-cultured ‘stem cell’ lineages in highly specific models and very carefully controlled conditions.
Sadly, the media is now rife with misleading and disingenuous adverts from people claiming to be able to ‘cure arthritis’ with simply ‘stem cell’ injections. Some of these companies are trying to swerve scientific criticism by referring to the cells they use as ‘stem cell precursors’, or other similarly meaningless terms. Their claims are backed up by references to ‘science’ and ‘research’, but their claims are false and empty, as there is no actual scientific evidence to substantiate their statements.
When cells are taken either from fat tissue or from bone marrow, only a very tiny percentage of these cells are actually genuine MSCs. The reality is that the cells are a disparate mix of all kinds of different cell types, and the ‘stem cell’ injections that are currently being touted to patients for clinical use, privately, are really nothing of the sort. Even if these injections did contain large numbers of MSCs, there is no scientific evidence at all that just injecting cells into a badly damaged arthritic joint will actually in any way reverse the arthritic damage at all. If one simply injects just saline into a painful knee then up to 40 per cent of people will report some degree of improvement, simply from the power of the placebo effect.
From a patient’s perspective, if you’re told that you’ve got an arthritic knee and that you’re going to need a knee replacement, this is a big deal. As people develop knee arthritis their function becomes limited and they start to lose the ability to continue with the kinds of exercise and sport that they might love. Also, knee replacement surgery itself is a major surgical procedure, involving pain, time off work, a long time to recover and rehabilitate afterwards, and not-insignificant potential risks, with no guarantees of a successful outcome. Therefore, it is entirely understandable that people should fall for the false promises of a quick fix and an easy ‘miracle cure’. Who wouldn’t be attracted by a potential treatment for knee arthritis that is cheaper than a knee replacement, that is far less painful, far less invasive, gives far quicker ‘results’ and carries much lower risks?
However, apart from people spending £6,000+ on treatments, are there any potential risks to the patient’s health? Well the answer here is a clear ‘yes’. For those techniques where periumbilical fat is harvested, there are all the usual potential risks of liposuction, which include infection, haematoma formation and even bowel perforation. Then, there are small but potentially serious risks from the actual joint injections themselves, with the most serious being the risk of potentially causing an infection in the joint (septic arthritis).
The biggest risk (guarantee), however, is that the patient will simply be suffering pain and hassle for no good reason when they could have been pursuing other proper evidence-based treatments.
Many of the adverts for these ‘stem cell’ treatments state that the treatment is ‘scientifically proven’ with ‘extensive research’. However, there is no proper evidence behind these treatments, and the one recent publication that is being cited is nothing more than a marketing questionnaire of 20 patients reporting satisfaction rates, but with no control group and no actual ‘science’.
So, you may well ask just how on Earth this kind of scandal can have been allowed to gain footage unabated within the UK private healthcare system? The fault lies not just with the individuals involved, but also very much with the regulatory authorities who have so far failed to fulfil their statutory duties to protect the public.
The Medicines and Healthcare Products Regulatory Agency (MHRA) are meant to regulate the use of ATMPs (Advanced Therapy Medicinal Products), and this includes the use of ‘stem cell’ type therapies. A cell therapy is classified as an ATMP if the cells are either manipulated in any way or if they are used heterologously, meaning that one cell type is used to try and replace another cell type. This very much applies to cells from fat tissue that are injected into a joint to allegedly ‘regrow’ cartilage tissue.
In the US, the Food and Drug Administration has been shutting down ‘stem cell clinics’ and prosecuting the directors. In the UK, the MHRA has so far failed to intervene.
There are some genuine options available for patients with early/impending knee arthritis who might want to try and delay (but not necessarily avoid) the eventual requirement for knee replacement surgery, and these include:
Meniscal transplantation.
If a meniscus is torn and de-functioned, or removed, then this leads to a very significant increased risk of arthritis in that compartment of the knee. However, if a meniscus is missing and if a patient is suffering post-meniscectomy pain from pressure-overload and early wear and tear of the articular cartilage, then the missing meniscus can be replaced by meniscal allograft transplantation.
Meniscal transplantation reduces pain, maintains patients’ function and helps them keep their knee going for longer, delaying the time when knee replacement surgery might become necessary. The first case series of meniscal transplants was reported in 1989 by Milachowski, [1] and since then thousands of papers have been published on the subject, with clinical results up to 26-year follow-up now available. [2]
Articular cartilage grafting.
Autologous Chondrocyte Implantation (ACI) was first performed by Lars Peterson and his team in Sweden in 1987, and since then the techniques for growing and implanting new articular cartilage cells into a knee have evolved, with the latest and most widely favoured version currently being Matrix-induced Chondrocyte Implantation (MACI).
Again, there are thousands of published papers available on the subject of ACI/MACI, and to-date it has been performed in at least 30,000 patients worldwide. In a review of 82 published studies, an overall success rate of 94.2 per cent was reported.[3]
Due to the high costs associated with ACI/MACI and the difficult and complex logistics involved (and also in no small part due to its lack of availability in many countries), alternative single-stage procedures have been developed for articular cartilage replacement, using bioabsorbable synthetic scaffolds such as Chondrotissue or Chondro-Gide. Encouraging results have been published, with 5+ year outcomes reported, and this field continues to evolve.[4]
‘Biological Knee Replacement’.
The term ‘biological knee replacement’ (or ‘BioKnee’) is a term popularised by Dr Kevin Stone, from San Francisco, who is one of the pioneers of complex reconstructive knee surgery. The term simply refers to cases where meniscal allograft transplantation and articular cartilage grafting procedures are combined together in the same knee, simultaneously. This is major complex surgery that is only undertaken by a very small number of the best and most experienced soft tissue knee surgeons as ‘salvage surgery’ in the most difficult of cases, where the alternative option of simply going for a knee replacement is not viable due to the patient being too young.
There is an urgent need for proper robust regulation of the healthcare market when it comes to novel cell therapies. There is an urgent need for patients to be protected from hype, the false claims and the disingenuous glossy marketing. What is needed are proper clinical trials and the carefully controlled introduction of innovative technology in a responsible and safe manner.[5]
The future of surgery lies in regeneration, with cells, scaffolds and growth factors all working in harmony in the development of true tissue engineering. We must all act to protect genuine scientific and clinical progress so that effective and appropriate treatment options are not tarred with the same brush as the fake ‘cure-all tonics’.
In the meantime, knee surgeons across the country will continue to be asked the same repeated question time and again: “Can’t you just inject my knee with stem cells, doc?”
References
- Milachowski KA, Weismeier K and Wirth CJ. Homologous meniscus transplantation. International Orthopaedics 1989; 13(1): 1-11
- El-Attar M, Dhollander A, Verdonk R, Almqvist KF and Verdonk P. Twenty-six years of meniscal allograft transplantation: is it still experimental? A meta-analysis of 44 trials. Knee Surgery Sports Traumatology Arthroscopy 2011; 19(2): 147-157
- Harris JD, Siston RA, Brophy RH, Lattermann C, Carey JL, Flanigan DC. Failures, re-operations, and complications after autologous chondrocyte implantation – a systematic review. Osteoarthritis Cartilage 2011; 19:779-791.
- Rodeo S, Haddad FS. Regenerative Solutions. The Bone and Joint Journal 2019; 101: 1033-1034
About the author:
Mr Ian McDermott is a full-time private Consultant Orthopaedic Surgeon based in Central London, specialising purely in knees. He is the founder of London Sports Orthopaedics, he is an Honorary Professor Associate at Brunel University, he is the President of the UK Biological Knee Society and he is also the Vice-Chairman of The Federation of Independent Practitioners Organisations.
For further info or to contact him, visit:
www.kneesurgeon.london or www.sportsortho.co.uk
