Frontiers in Aging Publishes a Review of How Cellular Senescence Reduces the Reliability of Cell Therapy

Frontiers in Aging Publishes a Review of How Cellular Senescence Redces the Reliability of Cell Therapy

On August 17, 2026, Frontiers in Aging published a review of mesenchymal stromal cells (MSCs), which are being studied for tissue repair and inflammation control. The authors explain why basic quality control is sometimes insufficient: a product may appear viable yet perform less effectively in its intended therapy.

The review traces the cell product from the donor through culture, freezing, transport, and thawing before administration. The cells may experience stress at every stage. Cellular senescence is a persistent state in which cells divide less often, alter their metabolism, and change the signals they send to surrounding tissue. In this state, a batch is less able to perform the function required for a specific therapy.

“A product may retain acceptable viability and conventional surface markers after it has already lost an important part of its function,” the authors write.

The review describes a sequence through which stress leads to loss of function. A prolonged cellular response to DNA damage slows cell division. Mitochondrial dysfunction increases the level of reactive oxygen species, which are reactive molecules that damage DNA and proteins. Mitochondria are cellular structures that produce energy. Changes in gene regulation, the removal of damaged proteins, and the signals released by the cell help maintain this state. As a result, MSCs become less able to proliferate, reach damaged tissue, regulate the immune response, and support tissue repair.

The starting point of this sequence depends on the cell source. For bone marrow MSCs, donor age and inflammation in the bone marrow are important. Umbilical cord cells are generally younger, but they are affected by culture, freezing, thawing, and transport. For adipose tissue MSCs, donor obesity, diabetes, and metabolic inflammation are important. Batch testing therefore needs to determine whether the cells retain the functions for which the product was prepared.

The authors propose matching each test to the product’s intended use. For a product designed to suppress inflammation, testing could determine whether the cells inhibit activated T cells, which are immune cells that initiate an immune response. For tissue repair, testing could assess vascular cell migration or the release of factors that support blood vessel growth. Combined with rapid measurements after thawing, such testing indicates whether the batch has retained the activity for which it was prepared.