Introduction: ICH is a fatal event in brain trauma and hemorrhagic stoke. In a patient who survives the initial ictus, the resulting hematoma in brain parenchyma triggers a series of events that lead to severe neurological deficits. Previous studies suggested that MSCs transplanted into the rat brain with ICH improved neurological function. However, there are still challenges remained in cell-based therapy using MSCs. Firstly, currently available MSCs have a limited lifespan in an in vitro culture condition, which restricts their clinical use. Secondarily, the neurological recovery may be found even one month after MSC transplantation.
Methods: We introduced pcMSCs to a rat model of ICH and examined their therapeutic potential. Adult male rats were subjected to ICH by intrastriatal injection of collagenase IV and then in situ transplanted with pcMSCs at 3 hrs after ICH. Collagenase IV injection induced hematoma accompanied by obvious edema, as revealed by MRI, in the brain parenchyma, which mimics clinical ICH pathology.
Results: Compared with the fibroblasts and the PBS control, hAMSCs treatment significantly promoted neurological recovery, and reduced the numbers of ED1(+) activated microglia, as well as myeloperoxidase (MPO(+)), and caspase-3(+) cells in the brain injury model. In addition, hAMSCs treatment significantly increased the expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the injured brain, and promoted neurogenesis and angiogenesis, compared with the fibroblasts and the PBS control. The transplanted hAMSCs survived for at least 27 days and were negative for ß-tubulin III and glial fibrillary acidic protein (GFAP).
Conclusions: PcMSC transplantation significantly promoted neurological recovery, as assessed by rotarod and other behavior tests, which was found 3 days after treatment. Conclusively, pcMSCs are candidate stem cells for the treatment of ICH. The possible mechanisms of action are under characterization.
Patient Care: To achieve standardized methods of MSCs isolation, characterization and administration to improve ICH treatments with MSCs.
Learning Objectives: We examined the therapeutic potential of hAMSCs in a rat model of ICH, and characterized the possible mechanisms of action. The mechanism of action could be mediated by inhibition of inflammation and apoptosis, increasing neurotrophic factor expression, and promotion of neurogenesis and angiogenesis.
References: 1. Shimamura N, Kakuta K, Wang L, Naraoka M, Uchida H, Wakao S, Dezawa M, Ohkuma H. Neuro-regeneration therapy using human Muse cells is highly effective in a mouse intracerebral hemorrhage model. Exp Brain Res. 2017 Feb;235(2):565-572.
2. Wang SP, Wang ZH, Peng DY, Li SM, Wang H, Wang XH. Therapeutic effect of mesenchymal stem cells in rats with intracerebral hemorrhage: reduced apoptosis and enhanced neuroprotection. Mol Med Rep. 2012 Oct;6(4):848-54.