Stem cells run like clockwork for stroke therapeutics

Stem cell therapy has shown promising therapeutic effects in stroke treatment. Recently, circadian rhythm has been implicated in the stroke incidence. Elucidating whether circadian rhythm also manifests in stem cells may optimize the outcomes. Here, we explored the interaction between circadian rhythm and stem cells in vitro. Cell velocity and proliferation of the umbilical cord-derived mesenchymal stem cells (UC-MSCs) were tracked by live cell imaging. We measured the levels of clock genes, BMAL1 and PER2, along with the proliferative marker, c-FOS, and the cytoskeletal marker, F-actin along the rhythm. Awake, semi-awake, and asleep UC-MSCs were co-cultured with human neurons subjected to oxygen-glucose deprivation (OGD). Results revealed that UC-MSCs exhibited patterns of cell activities and gene expressions resembling circadian rhythm. Awake UC-MSCs exerted greater protection of hypoxic neurons compared to asleep or semi-awake cells. As F-actin expression resembled awake UC-MSCs oscillation patterns and the therapeutic outcomes, cytoskeletal remodeling may involve in the stem cell circadian rhythm. Integrating circadian rhythm with stem cell therapy may fine-tune the regimen in restoring neurological functions.