朱剑虹：细胞治疗和细胞器置换技术用于神经系统疾病和损伤的预防和治疗
The current cell therapy aims at restoring neural regeneration and replacement of lost neural cells within the appropriate time window in traumatic brain injury patients. Furthermore, neurorepair attempts to restore retinal neuron axonal function in the optic nerve injury in those patients with significant visional impairment.
Mitochondria – bacteria sized cellular organelles residing in most of our cells-- convert fuel from food into the body's most biologically useful form of energy or ATP. Only in the past few years, with advances in cellular and molecular biology, have we appreciated the complexity of genetic mechanisms and cl inical presentations in mitochondrial disorders. For example, large numbers of mitochondria DNA (mtDNA) deletions in brain and muscle, become fatal or in young adulthood with epilepsy, while a maternally inherited point mutation in patients with Leber's hereditary optic neuropathy, a cause of blindness in young adults. Mutated mtDNAs may also have roles in the progressive symptoms of late-onset neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases.
Currently, these diseases are refractory or incurable; however, nuclear genome transfer between patients' and healthy eggs to replace mutant mtDNAs holds promises. Considering that a polar body contains few mitochondria and shares the same genomic material as an oocyte, we perform polar body transfer to prevent the transmission of mtDNA variants.
We compare the effects of different types of germline genome transfer, including spindle-chromosome transfer, pronuclear transfer, and polar body transfer, in mice. Genetic analysis confirms that the F1 generation from polar body transfer possesses m i n i m a l d o n o r m t D N A c a r r y o v e r . M o r e o v e r , t h e m t D N A g e n o t y p e r e m a i n s stable in F2 progeny after polar body transfer. Our investigation demonstrates that promising pre-clinical studies of cell therapy have been translating partially into positive outcomes in clinical trials, and mitochondrial replacement has great potential to prevent inherited mitochondrial diseases.
从多能干细胞到神经元和星形胶质细胞—模拟人类神经系统疾病
从人类多能干细胞(hPSCs)衍生的成熟神经元和神经胶质细胞，已成为对神经系统的发展和疾病研究的一个生理学相关模型。这些细胞的推导已超过了“概念验证”的阶段，并正在改变研究人员构建疾病模型和药物研发的方法。本网络研讨会将探讨学习如何从正常和患病的iPS细胞，生成脑型神经元、多巴胺能神经元和星形胶质细胞。Xianmin Zeng博士将介绍如何在毒理学研究和帕金森氏病的机制行动研究中成功地使用生成的神经元和胶质细胞。