Extending the Lifespan of Human Mesenchymal Stromal Cells: Approaches to Immortalization and Clinical Prospects.

Abstract

Mesenchymal stromal cells (MSCs) have a limited proliferative lifespan associated with replicative senescence, although the extent and onset of replicative senescence may vary among MSC sources. The immortalization of MSCs is being investigated as a strategy to extend proliferative capacity and facilitate scale-up. Moreover, immortalization may reduce the need for repeated isolation and expansion of primary MSCs, potentially facilitating the generation of sufficient cell numbers for research and manufacturing. Standardizing efficient methodologies remains important for consistent GMP manufacturing, product stability, and clinical translation. This review focuses on diverse strategies employed over the past 10 years to generate immortal MSCs, including induced pluripotent stem cell (iPSC)-derived sources and MSC-derived approaches. To determine whether the generated immortalized MSCs are functionally equivalent to primary MSCs, current trends and studies in the R&D phase are briefly discussed. Furthermore, this review highlights the underreported baseline stability assays and the need for comprehensive stability validation in the R&D phase. Additionally, the therapeutic potential of immortal MSCs is discussed, with an emphasis on their prospective applications in cell-based therapies and outlining future directions for their development.