Article Impact Level: HIGH Data Quality: STRONG Summary of Molecular Therapy, 33(1), 375–400. https://doi.org/10.1016/j.ymthe.2024.12.006 Dr. Barbara Klein et al.
Points
- The transplantation of hMSC-SB623 cells in a rat model of ischemic stroke significantly reduced stroke-induced cortical hyperexcitability and restored regular cortical network activity.
- The therapy promoted neuroregenerative effects by upregulating factors essential for synaptic and cellular plasticity, aiding brain repair.
- Blood analyses showed that hMSC-SB623 transplantation reversed stroke-related adverse effects on peripheral blood markers, demonstrating systemic immunomodulatory benefits.
- Despite the limited survival of transplanted cells in the brain, the treatment produced durable improvements in brain function and recovery.
- The findings highlight hMSC-SB623’s promise for treating chronic neurological conditions involving network hyperexcitability, such as stroke, epilepsy, and traumatic brain injury, warranting further research on its mechanisms and broader applications.
Summary
This study investigated the effects of allogeneic-modified bone marrow-derived human mesenchymal stromal/stem cells (hMSC-SB623) on stroke-induced cortical network excitability and peripheral blood markers in a rat model of ischemic stroke. One month after a focal ischemic stroke, rats were treated with either hMSC-SB623 cells or a vehicle solution. Cortical excitability was assessed starting one week post-treatment, with results showing that hMSC-SB623 cell transplants significantly reduced stroke-induced cortical hyperexcitability, restoring it to normal levels. The transplantation also induced neuroregenerative effects, including the upregulation of synaptic and cellular plasticity factors, which are essential for brain repair.
The study further examined the therapy’s immunomodulatory effects through blood-based analyses. Whole-blood RNA sequencing and serum protein analyses revealed that hMSC-SB623 cell transplantation reversed the adverse effects of stroke on peripheral blood markers related to stroke pathophysiology. These findings underscore the potential of hMSC-SB623 cells for restoring cortical network balance and for exerting far-reaching immunomodulatory effects that could aid in long-term stroke recovery. Despite only a tiny fraction of the transplanted human cells remaining in the brain, the beneficial effects on brain function were long-lasting.
The results of this study suggest that hMSC-SB623 cell transplantation holds promise for correcting stroke-induced circuit disruptions, even at the chronic stage. These findings are particularly relevant for therapeutic strategies targeting neurological conditions with network hyperexcitability, such as stroke, epilepsy, and traumatic brain injury. Further research is needed to fully understand the mechanisms underlying the therapy’s effects and broader applications, including its potential to stimulate brain repair and recovery in chronic neurological deficits.
Link to the article: https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(24)00807-4
References Klein, B., Ciesielska, A., Losada, P. M., Sato, A., Shah-Morales, S., Ford, J. B., Higashikubo, B., Tager, D., Urry, A., Bombosch, J., Chang, W.-C., Andrews-Zwilling, Y., Nejadnik, B., Warraich, Z., & Paz, J. T. (2025). Modified human mesenchymal stromal/stem cells restore cortical excitability after focal ischemic stroke in rats. Molecular Therapy, 33(1), 375–400. https://doi.org/10.1016/j.ymthe.2024.12.006
