Oligodendrocyte Precursor Cell Therapy Improves Stroke Recovery in Mice

Regenerative therapies capable of improving functional recovery following brain injury, such as that caused by stroke, are a priority in the research community. Cell therapies make up a sizable fraction of the research and development programs aimed at that goal. Here, researchers note the results of delivering oligodendrocyte precursor cells to the stroke-damaged mouse brain. Oligodendrocytes are involved in maintenance of the myelin sheathing necessary for nerve function, but introducing their precursor cells clearly produces a greater range of benefits, beyond increased remyelination, in the scenario of a brain injury.

Ischemic-induced white matter injury is strongly correlated with the poor neurological outcomes in stroke patients. The transplantation of oligodendrocyte precursor cells (OPCs) is an effective candidate for enhancing re-myelination in congenitally dysmyelinated brain and spinal cord. Nevertheless, mechanisms governing the recovery of white matter and axon after OPCs transplantation are incompletely understood in ischemic stroke.

In this study, OPCs were transplanted into the ischemic brain at 7 days after transient middle cerebral artery occlusion (tMCAO). We observed improved behavior recovery and reduced brain atrophy volume at 28 days after OPCs transplantation. Moreover, our results identified that myelin sheath integrity and endogenous OPCs proliferation and migration were promoted after OPCs transplantation. In addition, the improvement of neurite growth and synaptogenesis after OPCs transplantation in ischemic brain or OPC co-cultured neurons, potentially through the upregulation of Netrin-1, was indicated by increased protein levels of synaptophysin and postsynaptic density protein 95.

In conclusion, our studies suggested that engrafted OPCs promoted the recovery after ischemic stroke by enhancing endogenous oligodendrogenesis, neurite growth, and synaptogenesis; the last two being mediated by the Netrin-1/DCC axis.

Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612617/

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