title: Soliciting strategies for developing cell-based reference materials to advance mesenchymal stromal cell research and clinical translation.
abstract: The mesenchymal stromal cell (MSC) field continues to rapidly progress with a number of clinical trials initiated and completed, with some reported successes in multiple clinical indications, and a growing number of companies established. The field, nevertheless, faces several challenges. Persistent issues include the definition of a MSC and comparability between MSC preparations. This is because of inherent cell heterogeneity, the absence of markers that are unique to MSCs, and the difficulty in precisely defining them by developmental origin. Differences in the properties of MSCs also depend on the site of tissue harvest, phenotypic and genotypic characteristics of the donor and the isolation, and storage and expansion methods used. These differences may be sufficient to ensure that attributes of the final MSC product could differ in potentially significant ways. Since there are currently no gold standards, we propose using a reference material to establish methods of comparability among MSC preparations. We suggest four possible "ruler scenarios" and a method for global distribution. We further suggest that critical to establishing a reference material is the need to define protocols for comparing cells. The main purpose of this article is to solicit input in establishing a consensus-based comparison. A comparative approach will be critical to all stages of translation to better clarify mechanisms of MSC actions, define an optimal cell manufacturing process, ensure best practice clinical investigations, extend the use of an MSC product for new indications, protect an MSC product from imitators, and develop uniform reimbursement policies. Importantly, a reference material may enable a consensus on a practical definition of MSCs.
authors.affiliation: 1 Cell Therapy Program, University Health Network , Toronto, ON, Canada .
authors.forename: Sowmya
authors.initials: S
authors.lastname: Viswanathan
authors.forename: Armand
authors.initials: A
authors.lastname: Keating
authors.forename: Robert
authors.initials: R
authors.lastname: Deans
authors.forename: Peiman
authors.initials: P
authors.lastname: Hematti
authors.forename: Darwin
authors.initials: D
authors.lastname: Prockop
authors.forename: David F
authors.initials: DF
authors.lastname: Stroncek
authors.forename: Glyn
authors.initials: G
authors.lastname: Stacey
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Weiss
authors.forename: Christopher
authors.initials: C
authors.lastname: Mason
authors.forename: Mahendra S
authors.initials: MS
authors.lastname: Rao
mesh_terms: D018070:Biological Specimen Banks / Q000592:standards; D035843:Biomedical Research / Q000379:methods* / Q000639:trends; D018929:Cell Culture Techniques / Q000379:methods / Q000592:standards*; D032921:Consensus; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods* / Q000592:standards*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D012015:Reference Standards; D057170:Translational Research, Biomedical / Q000379:methods* / Q000639:trends