Real-time quality control and functional assessment of mesenchymal stem cells for cellular therapies

Abstract

Background & Aim One of the biggest hurdles in manufacturing of cellular therapies using mesenchymal stem cells (MSCs) is the lack of quantitative tools that simultaneously assess quality and potency of MSCs, which display big variations among donors and over limited passages. Methods, Results & Conclusion We developed a real-time cell-based assay that generates impedance signals reflecting integrated changes in cell number, attachment, and morphology. We obtained bone marrow derived MSCs from 3 different donors and cultured them under standard conditions using xeno-free media. Multiple real-time quantitative parameters are derived from the assay for quality control, such as proliferation kinetics, doubling time and maximal proliferation signal obtained. These parameters not only provided a measurement of quality of the cells but also provided useful in predicting the differentiation potential of the cells into various lineages including adipocytes, chondrocytes and osteoblasts. This label-free technology can be multiplexed with the measurement of functional biomarkers including receptor activation for a rapid and quantitative assessment of differentiation potential. Using this innovative system, we characterized inter- and intra- donor variability over multiple passages. Our findings suggest that the multi-parametric assay can provide the end-user with a comprehensive assessment for quality control whilst rapidly predicting the extent of functional activity of the cell during the manufacturing process.