Table 2.
Studies on the effects of early administration of normal MSCs or genetically engineered MSCs after SE
| Author | Type and characteristics of animal model used | Timing of intervention with cells after Insult | Type of cells infused and route of administration | Outcome measures examined | Major findings |
|---|---|---|---|---|---|
| Voulgari-Kokota et al. [71] | Mouse model of SE, induced through intraperitoneal injection of kainic acid | 24 hours after SE | Mouse MSCs expressing EGFP | Histopathology at 7-days postgrafting | No signs of engrafting of MSCs into the brain |
| Intravenous treatment | Reduced neuronal loss and diminished activation of astrocytes and microglia | ||||
| Abdanipour et al. [72] | Rat model of SE, induced through intraperitoneal administration of pilocarpine | 24 or 36 hours after the first seizure | Autologous MSCs Intravenous treatment | Measurement of behavioral seizures for 3 weeks postgrafting | 66% reduction in behavioral seizures |
| Shetty et al. [73] | Rat model of SE, induced through graded intraperitoneal injections of kainic acid | An hour after the induction of SE | Human bone marrow derived MSCs | Neurodegeneration and neuroinflammation in the hippocampus | Protection of principal neurons |
| Intraperitoneal administration | Reduced loss of GABA-ergic interneurons | ||||
| Normal levels of proinflammatory cytokines | |||||
| Reduced concentration of myeloperoxidase | |||||
| Enhanced expression of genes encoding anti-inflammatory cytokines | |||||
| Reduced numbers of ED-1+ activated microglia | |||||
| Li et al. [74] | Mouse model of hippocampus CA3 lesion, induced through microinjection of kainic acid into the amygdaloid nucleus | 24 hours after SE | Human MSCs (engineered to release adenosine). Implanted stereotactically into the infrahippocampal fissure | 16 hours of continuous EEG recordings (3 weeks after grafting) | Significant reduction in seizure intensity with reversal of effect after A1R antagonist treatment |
| Histology | Grafted cells survived and were restricted to the implanted infrahippocampal fissure | ||||
| Long et al., 2013 [75] | Rat model of SE, induced through intraperitoneal injections of lithium chloride and pilocarpine | 2 hours after the induction of SE | MSCs expanded from rat bone marrow engineered to suppress Hes1 gene | Behavioral observation and EEG monitoring | Decreased mortality, reduced epileptiform waves and EEG bursts in grafted animals |
| Survival | Smaller fraction of graft-derived cells gave rise to NeuN + and GAD-67+ cells in parahippocampal cortical areas at 7–14 days postgrafting | ||||
| Implanted stereotactically into the right lateral ventricle | Histology | No neuronal differentiation of graft-derived cells was seen in the hippocampus |
Abbreviations: A1R, adenosine 1 receptor; EEG, electroencephalogram; EGFP, enhanced green fluorescent protein; MSCs, mesenchymal stem cells; SE, status epilepticus.