Patients in many countries are exposed to dishonest offers of unproven cell interventions, referred to as “stem cell therapies” (SCT – stem cell transplantation – an abbreviation used exclusively in reference to unproven interventions, not evidence-based therapies based on stem cells). This problem is global, and the existing countermeasures have proven insufficient [1, 2]. Despite clear positions from international scientific organizations and regulatory agencies [3, 4, 5, 6] (e.g., ISSCR, European Medicines Agency, EASAC-FEAM, The InterAcademy Partnership), unregistered therapies are still available in some European countries.

This business has thrived by exploiting existing regulations, lack of patient and medical community awareness, and the growing hype surrounding stem cells, which are imprecisely portrayed as a panacea for incurable diseases. This can lead to the exploitation of legal loopholes and public ignorance for profit, even by leveraging legitimate approaches based on stem cells that are purportedly supportive of commercial offers [7].

Cell therapies used in Europe meet the definition of Advanced Therapy Medicinal Products (ATMP) based on cell therapy. The Committee for Advanced Therapies of the European Medicines Agency (CAT EMA) recommends verifying whether a gene-, cell-, or tissue-based product scientifically meets the definition of ATMP (Regulation No. 1394/2007). However, this recommendation does not imply that CAT EMA accepts ATMP therapies. In fact, in Europe, only Holoclar and Alofisel have active EMA registrations, in addition to a few registered gene therapy products based on autologous hematopoietic stem cells [8, 9].

Doubts about effectiveness and safety

In Poland, commercially offered cell products as ATMP-HE (Advanced Therapy Medicinal Products – Hospital Exemptions) are most commonly Wharton’s jelly cells, less frequently cells derived from adipose tissue or umbilical cord blood. The business clearly exploits gaps in current regulations, similar to other countries [11].

However, besides legal issues, there are also numerous biological and medical problems associated with unproven interventions. Firstly, Wharton’s jelly cells are in vitro expanded through serial passaging. They are allogeneic (from a different individual), but they can be administered without checking their immunological compatibility with patients. Such an approach is based on the widespread dogma that mesenchymal stem cells (MSCs) are particularly immunologically tolerant to patients, despite numerous studies showing that allogeneic MSCs trigger an immune reaction [12, 13]. In fact, the immune response can compound with the known rapid clearance of MSCs trapped in the lungs after intravenous administration, as living MSCs cannot be found a few hours after delivery [14].

Studies published by private institutions offering cell therapies do not meet scientific standards. Controlled clinical trials, control groups, proper patient monitoring methods, and data publications are often lacking [16, 17, 18, 19, 20]. Moreover, there is a lack of data regarding the efficacy and safety of these therapies. In some cases, serious side effects, such as vision loss, have been reported [15].

Landscape of commercial cell therapies in Poland

In Poland, SCT is advertised for various conditions, ranging from cosmetic applications to orthopedic issues, severe neurological diseases, developmental problems, and even hereditary blindness, muscular dystrophy, and infertility. Some of these applications, albeit in the minority – especially cosmetic and orthopedic ones – are offered by small private entities that usually use patient cells isolated from blood or adipose tissue (but also allogeneic cells derived from umbilical cord) as stem cells. The scale of these small firms is not fully known – one website advertises 35 private clinics in Poland offering stem cells, but the number mentioned is also 50 [10].

The cost of these cell therapies in Poland is very high. For example, three injections of Wharton’s jelly cells cost around 54,000 Polish zlotys (approximately 13,000 euros), and ten injections of mesenchymal cells can cost up to 237,000 Polish zlotys (approximately 55,000 euros) [10].

Unproven cell therapies in Poland pose serious risks and financial harm to patients and their families. There is also a conflict of interest as some academic doctors are involved in working for private clinics offering this type of therapy. Bioethical committees, which should assess experimental cell therapies, sometimes lack sufficient knowledge about stem cells and cell therapies. There is also a lack of registration of the side effects of these therapies in Poland (which poses a problem for compensation payouts) [10].

Impact of unproven cell therapies on patients

Supporters of SCT claim that their treatment is effective. However, patient testimonials, stories presented by doctors offering SCT (unsupported by research or clinical trial history), and publications of questionable quality provide doubtful evidence. Additionally, the reasons for the temporary improvement reported by patients cannot be verified since they may be receiving other treatments or undergoing rehabilitation alongside SCT at the same time. Concerns also arise regarding corticosteroids, which may be administered along with SCT, and patients may temporarily feel better after such treatment [10].

Unproven cell therapies are a global problem that also has its reflection in Poland. Commercial entities exploit the loopholes in ATMP-HE regulations, offering unproven cell interventions to patients. They advertise them as scientifically justified, compliant with legal regulations, and approved by bioethical committees. However, such practices are inconsistent with the recommendations of international scientific organizations and regulatory agencies, which clearly indicate insufficient evidence of effectiveness and safety for such therapies. Regulatory and educational actions are necessary to protect patients from unproven cell therapies.

Bibliography:

1. Master Z., Matthews K.R.W., Abou-El-Enein M. Unproven stem cell interventions: a global public health problem requiring global deliberation. Stem Cell Rep. 2021; 16: 1435-1445. https://doi.org/10.1016/j.stemcr.2021.05.004

2. Marks P.W., Hahn S. Identifying the risks of unproven regenerative medicine therapies. JAMA. 2020; 324: 241-242. https://doi.org/10.1001/jama.2020.9375

3. ISSCR. Guideliness for stem cell research and clinical translation. (https://www.isscr.org/guidelines) Date: 2021

4. European Medicines Agency. EMA warns against using unproven cell-based therapies.(https://www.ema.europa.eu/en/documents/public-statement/ema-warns-against-using-unproven-cell-based-therapies_en.pdf) Date: 2020

5. EASAC-FEAM. Challenges and potential in regenerative medicine: a joint report from EASAC and FEAM (https://easac.eu/publications/details/challenges-and-potential-in-regenerative-medicin/) Date: 2020

6. The Interacademy Partnership. The IAP statement on regenerative medicine. (https://www.interacademies.org/statement/iap-statement-regenerative-medicine) Date: 2021
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