Abstract
BackgroundMesenchymal stem or stromal cells are the most widely used cell therapy to date. They are heterogeneous, with variations in growth potential, differentiation capacity and protein expression profile depending on tissue source and production process. Nomenclature and defining characteristics have been debated for almost 20 years, yet the generic term ‘MSC’ is used to cover a wide range of cellular phenotypes. Against a documented lack of definition of cellular populations used in clinical trials, our study evaluated the extent of characterisation of the cellular population or study drug.MethodsA literature search of clinical trials involving mesenchymal stem/stromal cells was refined to 84 papers upon application of pre-defined inclusion/exclusion criteria. Data were extracted covering background trial information including location, phase, indication, tissue source and details of clinical cell population characterisation (expression of surface markers, viability, differentiation assays and potency/functionality assays). Descriptive statistics were applied, and tests of association between groups were explored using Fisher’s exact test for count data with simulated p value.ResultsTwenty-eight studies (33.3%) include no characterisation data. Forty-five (53.6%) reported average values per marker for all cell lots used in the trial, and 11 (13.1%) studies included individual values per cell lot. Viability was reported in 57% of studies. Differentiation was discussed: osteogenesis (29% of papers), adipogenesis (27%), and chondrogenesis (20%) and other functional assays arose in 7 papers (8%). The extent of characterisation was not related to the clinical phase of development. Assessment of functionality was very limited and did not always relate to the likely mechanism of action.ConclusionsThe extent of characterisation was poor and variable. Our findings concur with those in other fields including bone marrow aspirate and platelet-rich plasma therapy. We discuss the potential implications of these findings for the use of mesenchymal stem or stromal cells in regenerative medicine, and the importance of characterisation for transparency and comparability of literature.Graphical abstract
Highlights
Cell-based therapies, often using stem cell populations from adult tissues, offer substantial potential clinical benefits but represent considerable scientific and regulatory challenges in translation [1,2,3]
Non-haematopoietic stem cells have been identified in the bone marrow, with colony-forming, self-renewal and multi-lineage differentiation capacity demonstrated in vivo [4,5,6,7]
Overall, this study highlights the apparent paucity of characterisation data in Mesenchymal stem/stromal cell (MSC) clinical trial reports
Summary
Cell-based therapies, often using stem cell populations from adult tissues, offer substantial potential clinical benefits but represent considerable scientific and regulatory challenges in translation [1,2,3]. Non-haematopoietic stem cells have been identified in the bone marrow, with colony-forming, self-renewal and multi-lineage differentiation capacity demonstrated in vivo [4,5,6,7] These stem cells have acquired a more general identity in the literature, in which in vivo properties have been extrapolated to stromal cells from a wide range of tissues. MSC heterogeneity is well established and present at every level of analysis Compared to their bone marrow counterparts, stromal cells from the umbilical cord, cord blood, adipose, dental pulp, placenta and many other sources, exhibit differing marker profiles, differentiation potential and immunomodulatory properties [8,9,10]. Against a documented lack of definition of cellular populations used in clinical trials, our study evaluated the extent of characterisation of the cellular population or study drug
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