Pharmacological inhibition of circadian nuclear receptor REV-ERBs recovers mood disorders in Parkinson's disease of mouse model

摘要

Therapeutic effects of gene modified mesenchymal stem cells in chronic stroke Stroke is the major cause of death and disability worldwide. Despite numerous clinical and preclinical studies in the stroke arena, therapeutic approaches to treat chronic stroke are not prop- erly established. We previously reported that in acute phase of stroke, mesenchymal stem cells (MSCs) ameliorated stroke dam- age via mechanisms like immunomodulation and neuroprotection. In this study, we found that MSCs were unable to exert similar beneficial effect when transplanted in the chronic phase. Thus, we genetically modified MSCs using adenovirus encoding several genes and transplanted in the chronic stroke brain. Treatment with genetically modified MSCs significantly improved the behav- ioral and histological deficits when assessed with sensory-motor function tests and MRI respectively. Immuno-histochemical anal- yses indicated that transplantation of those genetically modified stem cells rejuvenated the microenvironment of the damaged brain tissue and activated the quiescent endogenous neural stem cells in a transgenic mouse model where neural stem/progenitor cells can be detected as EGFP. We also obtained similar results using in vitro studies indicating those cells exerted proangiogenic and pro-neurogenic effects. Our genetically modified MSCs, satisfied the STEP3 guidelines suggested for preclinical studies by FDA and NIH (2014), might provide a potential therapeutic strategy for the treatment of chronic stroke.