br and where there is a

…and where there is a longer road ahead Progress is being made at a rapid pace for certain neurodegenerative conditions such as Parkinson\'s disease and multiple sclerosis (MS), although based on different approaches. In the first case, the localized nature of neuronal damage suggested more than a decade ago that cell replacement therapy was a pursuable option. Roger Barker (University of Cambridge) presented an outstanding overview of research over the last twenty years, starting with the pioneering transplantation of foetal midbrain, to more recent approaches using neural stem inhibitor of catalase and ending with some of the challenges that the field currently faces and how they may be resolved (Barker et al., 2015). In contrast, MS, like most degenerative diseases of the central nervous system, affects extensive regions, making a complete cell replacement approach a major challenge. However, MS also well exemplifies how crucial it is to understand the molecular pathogenesis of a specific disease in order to devise meaningful and possibly efficacious therapies as discussed by Robin Franklin (University of Cambridge) and Gianvito Martino (San Raffaele, Milan). As mentioned above, localized versus widespread distribution of tissue damage remains a crucial issue in determining feasibility, outcome and how rapidly benefit may be reached. In this respect, another example reported at the conference was cell therapy for a localized form of muscular dystrophy (oculo-pharyngeal), which results in a modest but partially efficacious engraftment (Gill Butler-Browne, Myologie, Paris) (Périé et al., 2014), whereas systemic delivery of donor cells to patients affected by Duchenne muscular dystrophy, while safe and well-tolerated, produced a level of engraftment that was too low to produce significant efficacy (Giulio Cossu, University of Manchester), presumably due to the severity of the disease and the advanced age of the patients, selected for safety reasons (Cossu et al., 2015). Moving from skeletal to cardiac muscle, the landscape does not change: in this case, many clinical trials have been carried out in the past (Assmus et al., 2015) and were briefly described at the Conference. Simple cell transplantation is unlikely to be efficacious for either acute or chronic heart diseases. Indeed, different strategies were presented by Kenneth Chien (Karolinska, Stockholm) and Stefanie Dimmeler (University of Frankfurt) ranging from delivery of modified mRNA or miRNA to promote endogenous regeneration (Sahara et al., 2015) to in vitro models of various cardiac diseases created with induced pluripotent stem cell-derived cardiomyocytes (Joseph Wu, Stanford University) (Ebert et al., 2015). Likewise, in the case of muscular dystrophy, strategies to correct neighbouring resident nuclei (taking advantage of the multinucleated nature of the tissue) and combination with other gene/drug therapies appear as a possible way forward to overcome the major hurdle of poor engraftment. The scientific session on bone raised many issues and touched upon controversial topics. The bone marrow contains, in addition to the haematopoietic stem cells (HSCs), another population of adherent, clonogenic cells that have the ability to generate bone, cartilage and marrow fat; i.e., the cell types of the organ where they are resident. Such cells, usually referred to collectively as “mesenchymal stem cells” should rather be termed “skeletal stem cells” since they are specifically derived from bone (Bianco and Robey, 2015). In fact, cells with similar characteristics but different potency have been identified in many tissues of mesodermal origin. Despite their different specificities, such cells, are being utilized indiscriminately in hundreds of clinical trials worldwide, irrespective of their origin, and for a plethora of different diseases based on alleged immune modulatory and anti-inflammatory paracrine effects, often if not always in the absence of any real pre-clinical evidence, bio-distribution studies and rigorous endpoints to evaluate their efficacy (Bianco, 2014). The speakers of this session (Pamela Gehron Robey, NIH and Paolo Bianco, University of Rome) reiterated the clear difference between trials using these cells for repairing congenital or acquired diseases of cartilage and bone and the remaining, far less defined, questionable trials. The latter unfortunately tend to “evolve” progressively into uncontrolled and unapproved treatments offered by private stem cell clinics of questionable reputation to patients with incurable diseases, unable to make informed and non-emotional decisions. Even with rigorous trials, an accurate characterization of bona fide “mesenchymal stem cells” revealed that the preparations are significantly heterogeneous depending on the centre producing them. Nevertheless, positive results in repairing long bone defects (in conjunction with appropriate biomaterials) were reported by Frank Luyten, (Leuven University). A careful analysis of the pathogenesis of fibrous dysplasia also led to an important conclusion: if the underlying molecular mechanism is fully understood and drugable, cell replacement is not an obligatory route (Paolo Bianco, University of Rome).