Beyond genetic stability of mesenchymal stromal cells

Abstract

Mesenchymal stromal cells (MSCs) have been used in the clinic for more than a decade. However, this rapidly emerging area of research (352 clinical trials registered at ClinicalTrials.gov) is associated with much debate and controversy. A major issue is the safety and risk of transformation of MSCs during ex vivo expansion. Previous articles (1,2), now retracted (3,4), or analyses (5) reported the transformation or risk of transformation of MSCs from different sources during expansion. Although such transformation is likely a rare event (6,7), some genetic abnormalities, mainly aneuploidy, can appear during culture but are not related to the transformation per se (8). Consequently, from a regulatory point of view, we need to develop processes avoiding such transformation that use relevant controls to avoid the risk of transformation. A recent review, following a meeting of the European Medicines Agency in London to ensure the safety of MSC production, at least in pre-clinical settings, determined that cytogenetic abnormalities should be assessed (9). In this issue of Cytotherapy, three teams report on the genetic stability of ex vivo-expanded human MSCs. MSCs used in these studies came from three different sources: two from adult tissue [bonemarrow (BMMSCs) (10) and adipose tissue (ASCs) (11)] and one from a fetal source [chorionic villi (CV MSCs) (12)]. The culture processes differed. BMMSCswere expanded in a bioreactor (Quantum Cell Expansion System; Terumo BCT, Lakewood, CO, USA), and ASCs and CV MSCs were expanded in flasks. The media were similar, including fetal bovine serum, with the addition of conditioned medium for CV MSCs. Finally, a wide range of techniques were used to assess genetic stability, including conventional karyotyping,