Human adipose-derived mesenchymal stromal cells in vitro expansion for regenerative applications: tracking small genetic variants reveals dynamic changes within a genetically stable framework.

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background The extended use of mesenchymal stromal cells (MSC) for cellular therapies raises safety concerns, and preliminary controls are needed before clinical application to guarantee patient safety. In vitro expansion is frequently required to obtain sufficient material, with an increased risk of appearance and selection of genetically altered or senescent cells, which could impair not only safety but also the biological potential and therapeutic efficacy of these cells. In vitro manipulated MSCs must adhere to the guidelines of Good Manufacturing Practices including the verification of genomic stability, transformation potential and senescence. Several tests are currently used, mainly karyotyping, which enables the detection of large alterations. Small alterations, albeit potentially important, are usually not evaluated, except for selected known mutations in a few crucial genes. Methods Here, the potential of Next Generation Sequencing (NGS) to detect small DNA alterations was exploited as a reliable tool to monitor the genetic stability of cells manipulated prior to therapeutic application. The acquisition of small somatic mutations during in vitro culture of human adipose-derived mesenchymal stromal cells from 23 osteoarthritis patients was investigated at different times from passage 1 to passage 10 using targeted NGS of a panel of human cancer-related genes. Moreover,

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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