A tissue-engineered rostral migratory stream for directed neuronal replacement  

作　　者：John C.O'Donnell Kritika S.Katiyar Kate V.Panzer D.Kacy Cullen 

机构地区：[1]Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania [2]Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael Crescenz Veterans Affairs Medical Center [3]School of Biomedical Engineering, Drexel University [4]Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania

出　　处：《Neural Regeneration Research》2018年第8期1327-1331,共5页中国神经再生研究（英文版）

基　　金：supported by the National Institutes of Health[U01-NS094340(Cullen),F31-NS090746(Katiyar)&F32-NS103253(O’Donnell)];University of Pennsylvania[Center for Undergraduate Research&Fellowships(Panzer)];Michael J.Fox Foundation[Therapeutic Pipeline Program#9998(Cullen)];Department of Veterans Affairs[RR&D Merit Review I01-RX001097(Cullen)&BLR&D Merit Review I01-BX003748(Cullen)];the U.S.Army Medical Research and Materiel Command[W81XWH-16-1-0796(Cullen)]

摘　　要：New neurons are integrated into the circuitry of the olfactory bulb throughout the lifespan in the mamma- lian brain--including in humans. These new neurons are born in the subventricular zone and subsequently mature as they are guided over long distances via the rostral migratory stream through mechanisms we are only just beginning to understand. Regeneration after brain injury is very limited, and although some neuroblasts from the rostral migratory stream will leave the path and migrate toward cortical lesion sites, this neuronal replacement is generally not sustained and therefore does not provide enough new neurons to alleviate functional deficits. Using newly discovered microtissue engineering techniques, we have built the first self-contained, implantable constructs that mimic the architecture and function of the rostral migratory stream. This engineered microtissue emulates the dense cord-like bundles of astrocytic somata and processes that are the hallmark anatomical feature of the glial tube. As such, our living microtissue-en- gineered rostral migratory stream can serve as an in vitro test bed for unlocking the secrets of neuroblast migration and maturation, and may potentially serve as a living transplantable construct derived from a patient＇s own cells that can redirect their own neuroblasts into lesion sites for sustained neuronal replace- ment following brain injury or neurodegenerative disease. In this paper, we summarize the development of fabrication methods for this microtissue-engineered rostral migratory stream and provide proof-of-princi- ple evidence that it promotes and directs migration of immature neurons.New neurons are integrated into the circuitry of the olfactory bulb throughout the lifespan in the mamma- lian brain--including in humans. These new neurons are born in the subventricular zone and subsequently mature as they are guided over long distances via the rostral migratory stream through mechanisms we are only just beginning to understand. Regeneration after brain injury is very limited, and although some neuroblasts from the rostral migratory stream will leave the path and migrate toward cortical lesion sites, this neuronal replacement is generally not sustained and therefore does not provide enough new neurons to alleviate functional deficits. Using newly discovered microtissue engineering techniques, we have built the first self-contained, implantable constructs that mimic the architecture and function of the rostral migratory stream. This engineered microtissue emulates the dense cord-like bundles of astrocytic somata and processes that are the hallmark anatomical feature of the glial tube. As such, our living microtissue-en- gineered rostral migratory stream can serve as an in vitro test bed for unlocking the secrets of neuroblast migration and maturation, and may potentially serve as a living transplantable construct derived from a patient＇s own cells that can redirect their own neuroblasts into lesion sites for sustained neuronal replace- ment following brain injury or neurodegenerative disease. In this paper, we summarize the development of fabrication methods for this microtissue-engineered rostral migratory stream and provide proof-of-princi- ple evidence that it promotes and directs migration of immature neurons.

关 键 词：rostral migratory stream glial tube ASTROCYTE NEUROBLAST brain injury neural repair neural regeneration tissue engineering 

分 类 号：R651.15[医药卫生—外科学]