Regulation of stem cell therapies in Europe

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4 European renowned stem cell scientists published a commentary in the EMBO Journal taking a stand to a debate of a new law in the Italian Parliament. This new law would make it legal to practice an unproven stem cell treatment, in this specific case infusion of mesenchymal stem cells (MSCs), in public hospitals. So far rules set out by regulatory bodies like EMA (European Medicines Agency) or FDA (Food and Drug Administration) have been effective in protecting patients from serious risk associated with the indiscriminate use of “stem cells”. The scientists see today the risk that this may rapidly change.

The rapid development in the field of stem cell science has given rise to great hope and expectations but is confronted now with the pressure to effect the rapid translation from the bench to bedside. Cracking regulations open is the agenda of some companies wishing to market ‘stem cells’. Lobbying and pleading for accelerated ‘innovation’ and or ‘patients access to therapies’ are extensively used arguments to this end. These arguments mislead patients by suggesting that regulations, and the prudence of scientists and physicians, are against their best interest.

In Italy a campaign was started demanding and vowing the right of patients to have access to stem cell therapy. The campaign, supported by part of the press together with public statements of celebrities, claimed for a ‘compassionate therapy’ and was accompanied by an offence against scientists and their arguments.

In the commentary in the EMBO Journal the scientists make their position clear.

Premature translation of temporary data and concepts in the stem cell field, in conjunction with loosened regulation cannot provide solutions for diseases. Pressure for premature translation of unconvincing science can also encourage, albeit indirectly, practices that are destructive for patients.

There can be no compassionate therapy without respecting 1) safety and 2) efficacy.
Basically there is no therapy without adverse effects, cell therapies are no exception and cannot be considered safe in patients without been studied in monitored clinical trials.

Mesenchymal stem cells systemically administered are introduced in the bloodstream which is not the natural environment. It is not clear how exogenous MSCs will behave in the brain, the kidney or the lung and what adverse reactions can be triggered by MSCs.
Another safety aspect concerns the processing of the cells. Stem cells have to be defined as medicines because MSCs are generated and expanded in sufficient quantities for infusion into the patient by ex vivo culture and therefore have to be subject to regulatory agencies like the EMA or the FDA. Medicines need to be manufactured in highly controlled environments, with precise protocols because of specific risks. The argument that stem cells should be regarded as a transplant which is exempt from these regulations is not correct because of two reasons: a) transplants are not cultured ex vivo and b) intravenously administered MSCs rapidly disappear from the body like a drug and do not engraft.

Taking cell therapies out of these drug regulations is invoked by companies wishing to market cell therapies before their efficacy can be proven through trials. But formal clinical trials remain the only way to learn about new therapies, to do good to patients and to do no harm.

The scientists also disagree with the argument that safety “is not a concern in the face of severly ill patients, for whom there are no therapeutic alternatives.” because as they point out “Exposing the weakest people to unknown risk is ethically unacceptable and is not at all compassionate treatment.”

Also the argument that offering MSC treatments directly to patients are grounded in scientific rationale and with proven clinical efficacy is misleading.
The use of stem cells in medicine has to be justified by medical rationales concerning “not only the true biological nature of the type of cells considered for use but also the biology of the diseases being treated.” Stem cells are not a homogenous class of cells and are not one-size-fits-all cures. There are only a few examples of proven stem cell therapies, including bone marrow transplantation (haematopoetic stem cells), corneal resurfacing (limbal stem cells) and skin regeneration (epidermal stem cells). There is no rational justification for the use of MSCs in a range of diseases including neurodegenerative disease like Spinal Muscular Atrophy or Parkinson’s disease and other kinds of irreversible brain or spinal damage. The diseases differ strikingly from one another with respect to cause, mechanism and natural history.

The argument that the patients would benefit from the progenitor function of the MSCs implies the differentiation in neural cells and efficient replacement of either neurons or glial cells. But there are no sufficient robust scientific data for this expectation and a lot of unanswered questions.

The alternative argument for the use of MScs in different diseases is their ‘trophic, immune modulating, anti-inflammatory effects’. This statement is vague as the specific immunodulatory effects are not known. Before moving the treatment into clinical use the underlying mechanism and/or “any putative paracrine factor involved should be identified and then developed into a drug. Mechanistic insight is not a dispensable intellectual luxury… it is required to develop effective therapies”. The knowledge at this time does not justify the translation to the clinic in this stage.

The conclusion of the commentary is:

Stem cells may shape contemporary medicine, but only if they are properly evaluated in the lab and translated to the clinic at such time as the data supports this, and then only in trials that have rigor and proper regulatory oversight.
Breaching regulation undermines the protection of patients, paves the way for adventurers, disrupts public health care systems, destroys efforts towards sensible translation of science into medicine and wastes vital health care funds.


Regulation of stem cell therapies under attack in Europe: for whom the bell tolls.

Bianco P, Barker R, Brüstle O, Cattaneo E, Clevers H, Daley GQ, De Luca M, Goldstein L, Lindvall O, Mummery C, Robey PG, Sattler de Sousa E Brito C, Smith A.

EMBO J. 2013 May 29;32(11):1489-95. doi: 10.1038/emboj.2013.114. Epub 2013 May 3.