Enhanced therapeutic effect of intracavitary mesenchymal stromal cell administration with alginate scaffold in acute intracerebral hemorrhage model rat after hematoma aspiration.

In order to develop a novel treatment for intracerebral hemorrhage (ICH), the cavity formed after hematoma evacuation is reasonable therapeutic target, given that secondary brain injuries are triggered and evolve from this cavity. We conceived novel stem cell-based therapeutic strategy involving direct administration of mesenchymal stromal cell (MSC) into this cavity using ultra-purified alginate (ALG) gel scaffold. Herein, we tested its therapeutic potential in both in vitro and in vivo. In vitro, cell viability and brain-derived neurotrophic factor (BDNF) secretion capacity were compared between MSC cultured with ALG and MSC with saline, under both normal and pro-inflammatory conditions. In vivo, rat ICH model with hematoma aspiration was treated with intracavitary administration of saline, ALG-alone, MSC-alone, or MSC with ALG. Neurological function, brain atrophy, inflammatory reactions, apoptotic cell death, and brain BDNF levels were evaluated. In vitro, MSC with ALG exhibited significantly better cell viability and enhanced and sustained BDNF secretion than MSC-alone, even under pro-inflammatory conditions. In vivo, both MSC-alone and MSC with ALG treatment provided therapeutic benefit; however, MSC + ALG group showed significantly greater improvement in neurological recovery, and attenuation of brain atrophy, inflammation and apoptosis around the cavity. Furthermore, enhanced and prolonged BDNF upregulation was also observed in MSC + ALG group. These enhanced neuroprotective effects appear to be due to the prolonged viability and paracrine activity of MSC under hostile post-hemorrhagic conditions. While this novel therapy shows promise as a treatment for ICH, further studies are required to clarify its mechanisms and optimize clinical translation.