Circular RNA rejuvenates stem cells without erasing cell identity

Mesenchymal stem cells (cells that can develop into bone, cartilage, or fat tissue) are widely used in cell therapy. But repeated expansion in the lab ages them and reduces their potency. The researchers turned to partial reprogramming as a solution: they activated three Yamanaka factors (proteins that can return cells to an earlier developmental state) using circular RNA (RNA molecules with a ring-like structure that is stable and does not integrate into the genome).

Why the ring structure matters

Conventional reprogramming via Yamanaka factors carries risks: if applied for too long or at too high a level, it can push cells into a state where they divide without control. Circular RNA delivers the factors transiently and in a coordinated way, without modifying the DNA. The researchers demonstrated that their method, circ-OSK, did not convert the stem cells into induced pluripotent stem cells (cells that can grow indefinitely and may cause cancer).

After treatment with circ-OSK, aged stem cells showed fewer signs of cellular senescence: less DNA damage, reduced levels of the inflammatory signals that senescent cells secrete, and restored capacity to proliferate and migrate. Their identity as stem cells remained intact.

What the gene activity analysis showed

Analysis of gene activity patterns indicated that the rejuvenation was associated with suppression of the PI3K-Akt signalling pathway, a cell growth route implicated in aging and cancer. Genome analysis confirmed that the genetic material remained intact. The results were published in Stem Cell Research & Therapy. This is laboratory research; human applications require extensive further study.

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