title: An Innovative, Comprehensive Mapping and Multiscale Analysis of Registered Trials for Stem Cell-Based Regenerative Medicine.
abstract: We aim to provide an innovative, comprehensive way of mapping the profusion of stem cell-based clinical trials registered at ClinicalTrials.gov to explore the diversity of the fields of application and the temporal complexity of the domain. We used a chord diagram and phylogenetic-like tree visualizations to assist in data mining and knowledge discovery. The search strategy used the following terms: "stromal OR stem OR mesenchymal OR progenitor." The Medical Subject Headings (MeSH) thesaurus was used to more finely classify diseases treated by stem cells, from large fields of application to specific diseases. Of the 5,788 trials screened, 939 were included, 51.1% of which were related to mesenchymal stem cells (MSCs). No real specificity emerged as to the therapeutic uses of the different types of stem cells. More than half the MSC studies concerned allogeneic MSCs and received more support from industry than autologous MSC studies (p < .001). Over time, the uses of cultured cells have increased greatly, particularly since 2009. Cells derived from adipose tissue are also increasingly used in trials compared with bone marrow cells. The use of adipose-derived stromal cells was predominantly autologous (p < .001), restricted to European countries (p < .01), and supported by industry (p = .02) compared with other MSCs. Details about MeSH keywords are available at http://multireview.perso.sfr.fr/. In conclusion, mapping may reveal a lack of global strategy despite the regulations and the related costs associated with good manufacturing practices. A systematic approach to preclinical data, intended to objectively and robustly reveal the most appropriate fields with the most efficient cells, is needed. Repeated exchanges between the bench and the bedside are necessary.
  
  
  CONCLUSIONS
  Except for a few trials concerning specific tissue stem cells used in their corresponding tissues, this global analysis revealed no real specificity of stem cell uses (including mesenchymal stromal cells). This raised the question of the physiopathological rationale for these uses and the lack of a global strategy despite the regulations and the related costs associated with good manufacturing practices. This original method, leading to the development of new concepts from already available data, would help policymakers to optimize resources and investments in terms of public health priorities. Such an approach should draw parallels between in vitro, in vivo, and human data. Exchanges in both directions between preclinical and clinical research could optimize the parameters of clinical trials step by step.
authors.affiliation: Department of Anatomical Sciences and Radiology, Dental Faculty, Toulouse University Hospital, Toulouse, France STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm, UPS, Toulouse, France paul.monsarrat@gmail.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Monsarrat
authors.affiliation: Department of Epidemiology and Public Health, Dental Faculty, Toulouse University Hospital, Toulouse, France Division of Oral Health and Society, Faculty of Dentistry, McGill University, Montreal, Quebec, Canada.
authors.forename: Jean-Noel
authors.initials: JN
authors.lastname: Vergnes
authors.affiliation: STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm, UPS, Toulouse, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Planat-Bénard
authors.affiliation: Faculty of Medicine, Paris Descartes University, Paris, France Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York, USA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravaud
authors.affiliation: Department of Biological Sciences, Dental Faculty, Toulouse University Hospital, Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Kémoun
authors.affiliation: STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm, UPS, Toulouse, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Sensebé
authors.affiliation: STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm, UPS, Toulouse, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Casteilla
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics; D064987:Cell- and Tissue-Based Therapy; D002986:Clinical Trials as Topic; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D044968:Regenerative Medicine
keywords: Clinical trials as topic; Data mining; Mesenchymal stromal cells; Regenerative medicine; Stem cells