Regenerative medicine is an interdisciplinary field of research and clinical applications focused on the repair, replacement or regeneration of cells, tissues or organs to resort impaired function resulting from any cause, including congenital defects, disease, trauma and ageing. It uses a combination of several converging technological approaches, both existing and newly emerging, that moves it beyond traditional transplantation and replacement therapies. The approaches often stimulate and support the body’s own self-healing capacity. [Daar AS, Greenwood HL, 2007].
Albeit not new, the idea of restoring the impaired functioning of bodily structures through products of biological origin recently re-gained momentum as science proved able to experimentally control the proliferative and differentiative fate of human cells both in vitro and in vivo. These new manipulative abilities have led biomedical researchers to probe how stem cells could be harnessed to restore the functionality of human bodies.
The human body is already being used as materia medica in contemporary medicine. Familiar examples of regenerative medicine are blood transfusions and organ transplantations; bone marrow grafts for patients affected by hematological cancer represent the first stem cell therapy with success.
However, one main difference between these early examples of regenerative medicine and what stem cells might do in terms of bodily regeneration in the imminent future needs to be highlighted : the displacement of human cells from one body to another (heterologous treatment) or the re-implantation of cells extracted from the same patient (autologous treatment), is generally mediated by molecular-level manipulations that transform a given body “part” into the desired kind of entity that the receiving patient needs.
This manipulation can be both qualitative and quantitative: techniques now allow to both alter the identity of a given set of stem cells or to expand them, thus increasing their number up to the amount necessary for therapeutic use. Furthermore, in recent years, techniques have been developed to reprogram fully differentiated cells to a pluripotent state [Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al, 2007], from which they can subsequently be driven to any somatic lineage and, in theory, be used for therapy – thus avoiding the ethically contentious destruction of human embryos that was previously needed to obtain pluripotent stem cells.
Schematically, there exist three major modes of activity that can be exploited in cell-based regenerative medicine.
- Cells injected into a patient, whether they come from the same patient or from a donor, could provide a therapeutic function by either: secreting trophic factors and exerting an immunomodulatory activity (e.g. reducing localized inflammation);
- Replacing a piece of damaged cellular structure with or without the support of biomaterials and synthetic scaffolds (e.g. in chondrocyte-based cartilage replacement treatment);
- By reconstituting in vivo a cellular structure starting from the injection of stem cells that have the capacity to differentiate in an orchestrated and hierarchical fashion (e.g. neural stem cells for treating the effects of ischemic stroke).
In all the above cases the cells of origin can be stem cells, progenitors or differentiated cells, depending on the technical protocol chosen by the research team.
Arguably, the future of the field crucially depends on the development of safe and effective cell therapies and products, and thus relies as much on technical progress as it relies on the emergence of a common governance framework that is able to assure an ethically defensible and scientifically reliable translation of stem cells.
The gold standard for the validation of biomedical innovation in Western medicine is the standardized generation of knowledge through clinical trials conducted according to the epistemic principles of evidence-based medicine [Timmermans S, Berg M, 2003 ; Tournay V., 2005 ; Keating P, Cambrosio A., 2007, Keating P, Cambrosio A., 2012].
As a matter of fact, however, stem cell translation is a global enterprise featuring a number of actors racing to deliver as soon as possible their cellular products and therapies to the market. Different actors have different ideas about how stem cell biology should be translated into regenerative medicine.
Alongside technical uncertainties, regulatory gaps and a heterogeneous global legislative framework at EU level also affect the development of regenerative medicine, thus leaving the debate open about how public authorities should regulate this process, how patients should be involved and, finally, how this science should be exploited commercially. It is in this scenario that, in recent years, stem cell clinics have emerged offering stem cell treatments to thousands of patients, contrary to the advice of large sectors of the scientific community. Stem cell medicine centers are active in the US, in Europe and Central America, but most of these clinics are reported to be in Asia (especially in China) [Chen H, Gottweis H., 2011]. The typology of injected cellular products ranges from fetus-derived cells, to autologous adult stem cells of various origin, employed to treat a variety of conditions including arthritis, fatigue, Parkinson disease, stroke and sometimes cancer. Apart from the use of hematopoietic stem cells, the scientific community has been rather consistent in considering those treatments as scientifically unproven, medically unjustified, and ethically unwarranted, but an international market of adult stem cell therapies nevertheless arose.
Despite this climate of confusion, the whole pipeline from the drug discovery to the marketing authorization is a reality and will develop in the next future. EU has a major role to play to support these translational activities when at the same time it will have to ensure European patients’ security.