title: A relativity concept in mesenchymal stromal cell manufacturing.
abstract: Mesenchymal stromal cells (MSCs) are being experimentally tested in several biological systems and clinical settings with the aim of verifying possible therapeutic effects for a variety of indications. MSCs are also known to be heterogeneous populations, with phenotypic and functional features that depend heavily on the individual donor, the harvest site, and the culture conditions. In the context of this multidimensional complexity, a recurrent question is whether it is feasible to produce MSC batches as "standard" therapeutics, possibly within scalable manufacturing systems. Here, we provide a short overview of the literature on different culture methods for MSCs, including those employing innovative technologies, and of some typically assessed functional features (e.g., growth, senescence, genomic stability, clonogenicity, etc.). We then offer our perspective of a roadmap on how to identify and refine manufacturing systems for MSCs intended for specific clinical indications. We submit that the vision of producing MSCs according to a unique standard, although commercially attractive, cannot yet be scientifically substantiated. Instead, efforts should be concentrated on standardizing methods for characterization of MSCs generated by different groups, possibly covering a vast gamut of functionalities. Such assessments, combined with hypotheses on the therapeutic mode of action and associated clinical data, should ultimately allow definition of in-process controls and measurable release criteria for MSC manufacturing. These will have to be validated as predictive of potency in suitable pre-clinical models and of therapeutic efficacy in patients.
authors.affiliation: Department of Biomedicine, University Hospital Basel, Basel, Switzerland. Electronic address: ivan.martin@usb.ch.
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.affiliation: Merln Institute for Technology-inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: De Boer
authors.affiliation: UMR5273 STROMALab Centre National de la Recherche Scientifique (CNRS)/Établissement Français du Sang (EFS)/Universite Paul Sabatier (UPS), Institut National de la Sante et de la Recherche Médicale (INSERM), U1031, Toulouse, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Sensebe
mesh_terms: D018929:Cell Culture Techniques; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D016922:Cellular Senescence / Q000502:physiology; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged
keywords: MSCs; cellular therapy; clinical trial; manufacturing