Cellular transplantation for repair of spinal cord injury is a prom- ising therapeutic strategy that includes the use of a variety of neural and non-neural cells isolated or derived from embryonic and adult tissue as ...Cellular transplantation for repair of spinal cord injury is a prom- ising therapeutic strategy that includes the use of a variety of neural and non-neural cells isolated or derived from embryonic and adult tissue as well as embryonic stem cells and induced plu- ripotent stem cells. In particular, transplants of neural progenitor cells （NPCs） have been shown to limit secondary injury and scar formation and create a permissive environment in the injured spinal cord through the provision of neurotrophic molecules and growth supporting matrices that promote growth of injured host axons. Importantly, transplants of NPC are unique in their poten- tial to replace lost neural cells - including neurons, astrocytes,展开更多
The inhibitory sources in the thalamic nuclei are local interneurons and neurons of the thalamic reticular nucleus. Studies of models of absence epilepsy have shown that the seizures are associated with an excess of i...The inhibitory sources in the thalamic nuclei are local interneurons and neurons of the thalamic reticular nucleus. Studies of models of absence epilepsy have shown that the seizures are associated with an excess of inhibitory neurotransmission in the thalamus. In the present study, we used light- microscopic gamma-aminobutyric acid （GABA） immunocytochemistry to quantify the interneurons in the lateral geniculate （LGN）, ventral posteromedial （VPM）, and ventral posterolateral （VPL） thalamic nuclei, and compared the values from normal Wistar rats and genetic absence epilepsy rats from Strasbourg （GAERS）. We found that in both Wistar rats and GAERS, the proportion of interneurons was significantly higher in the LGN than in the VPM and VPL. In the LGN of Wistar rats, 16.4% of the neurons were interneurons and in the GAERS, the value was 15.1%. In the VPM, the proportion of interneurons was 4.2% in Wistar and 14.9% in GAERS; in the VPL the values were 3.7% for Wistar and 11.1% for the GAERS. There was no significant difference between Wistar rats and the GAERS regarding the counts of interneurons in the LGN, whereas the VPM and VPL showed significantly higher counts in GAERS. Comparison of the mean areas of both relay cells and interneuronal profiles showed no significant differences between Wistar rats and GAERS. These findings show that in the VPL and the VPM there are relatively more GABAergic interneurons in GAERS than in Wistar rats. This may represent a compensatory response of the thalamocortical circuitry to the absence seizures or may be related to the production of absence seizures.展开更多
The greatest challenge to successful treatment of spinal cord injury is the limited regenerative capacity of the central nervous system and its inability to replace lost neurons and severed axons following injury. Neu...The greatest challenge to successful treatment of spinal cord injury is the limited regenerative capacity of the central nervous system and its inability to replace lost neurons and severed axons following injury. Neural stem cell grafts derived from fetal central nervous system tissue or embryonic stem cells have shown therapeutic promise by differentiation into neurons and glia that have the potential to form functional neuronal relays across injured spinal cord segments. However, implementation of fetal-derived or embryonic stem cell-derived neural stem cell ther- apies for patients with spinal cord injury raises ethical concerns. Induced pluripotent stem cells can be generated from adult somatic cells and differentiated into neural stem cells suitable for therapeutic use, thereby providing an ethical source of implantable cells that can be made in an autologous fashion to avoid problems of immune rejection. This review discusses the therapeutic potential of human induced pluripotent stem cell-derived neural stem cell transplantation for treatment of spinal cord injury, as well as addressing potential mechanisms, future perspectives and challenges.展开更多
Spinal cord injury represents a devastating central nervous system injury that could impair the mobility and sensory function of afflicted patients.The hallmarks of spinal cord injury include neuroinflammation,axonal ...Spinal cord injury represents a devastating central nervous system injury that could impair the mobility and sensory function of afflicted patients.The hallmarks of spinal cord injury include neuroinflammation,axonal degeneration,neuronal loss,and reactive gliosis.Furthermore,the formation of a glial scar at the injury site elicits an inhibitory environment for potential neuroregeneration.Besides axonal regeneration,a significant challenge in treating spinal cord injury is to replenish the neurons lost during the pathological process.However,despite decades of research efforts,current strategies including stem cell transplantation have not resulted in a successful clinical therapy.Furthermore,stem cell transplantation faces serious hurdles such as immunorejection of the transplanted cells and ethical issues.In vivo neuronal reprogramming is a recently developed technology and leading a major breakthrough in regenerative medicine.This innovative technology converts endogenous glial cells into functional neurons for injury repair in the central nervous system.The feasibility of in vivo neuronal reprogramming has been demonstrated successfully in models of different neurological disorders including spinal cord injury by numerous laboratories.Several reprogramming factors,mainly the pro-neural transcription factors,have been utilized to reprogram endogenous glial cells into functional neurons with distinct phenotypes.So far,the literature on in vivo neuronal reprogramming in the model of spinal cord injury is still small.In this review,we summarize a limited number of such reports and discuss several questions that we think are important for applying in vivo neuronal reprogramming in the research field of spinal cord injury as well as other central nervous system disorders.展开更多
基金NIH PO1 NS055976,Craig H.Neilsen Foundation,and Shriner’s Hospital for Children
文摘Cellular transplantation for repair of spinal cord injury is a prom- ising therapeutic strategy that includes the use of a variety of neural and non-neural cells isolated or derived from embryonic and adult tissue as well as embryonic stem cells and induced plu- ripotent stem cells. In particular, transplants of neural progenitor cells （NPCs） have been shown to limit secondary injury and scar formation and create a permissive environment in the injured spinal cord through the provision of neurotrophic molecules and growth supporting matrices that promote growth of injured host axons. Importantly, transplants of NPC are unique in their poten- tial to replace lost neural cells - including neurons, astrocytes,
基金supported by Marmara University Scientific Research Council, Turkey (BGS-150107-0011)
文摘The inhibitory sources in the thalamic nuclei are local interneurons and neurons of the thalamic reticular nucleus. Studies of models of absence epilepsy have shown that the seizures are associated with an excess of inhibitory neurotransmission in the thalamus. In the present study, we used light- microscopic gamma-aminobutyric acid （GABA） immunocytochemistry to quantify the interneurons in the lateral geniculate （LGN）, ventral posteromedial （VPM）, and ventral posterolateral （VPL） thalamic nuclei, and compared the values from normal Wistar rats and genetic absence epilepsy rats from Strasbourg （GAERS）. We found that in both Wistar rats and GAERS, the proportion of interneurons was significantly higher in the LGN than in the VPM and VPL. In the LGN of Wistar rats, 16.4% of the neurons were interneurons and in the GAERS, the value was 15.1%. In the VPM, the proportion of interneurons was 4.2% in Wistar and 14.9% in GAERS; in the VPL the values were 3.7% for Wistar and 11.1% for the GAERS. There was no significant difference between Wistar rats and the GAERS regarding the counts of interneurons in the LGN, whereas the VPM and VPL showed significantly higher counts in GAERS. Comparison of the mean areas of both relay cells and interneuronal profiles showed no significant differences between Wistar rats and GAERS. These findings show that in the VPL and the VPM there are relatively more GABAergic interneurons in GAERS than in Wistar rats. This may represent a compensatory response of the thalamocortical circuitry to the absence seizures or may be related to the production of absence seizures.
基金supported by grants from the Veterans Administration and the California Institute for Regenerative Medicine
文摘The greatest challenge to successful treatment of spinal cord injury is the limited regenerative capacity of the central nervous system and its inability to replace lost neurons and severed axons following injury. Neural stem cell grafts derived from fetal central nervous system tissue or embryonic stem cells have shown therapeutic promise by differentiation into neurons and glia that have the potential to form functional neuronal relays across injured spinal cord segments. However, implementation of fetal-derived or embryonic stem cell-derived neural stem cell ther- apies for patients with spinal cord injury raises ethical concerns. Induced pluripotent stem cells can be generated from adult somatic cells and differentiated into neural stem cells suitable for therapeutic use, thereby providing an ethical source of implantable cells that can be made in an autologous fashion to avoid problems of immune rejection. This review discusses the therapeutic potential of human induced pluripotent stem cell-derived neural stem cell transplantation for treatment of spinal cord injury, as well as addressing potential mechanisms, future perspectives and challenges.
基金supported by startup funds from Medical College of Georgia at Augusta University(to HL)National Institutes of Health R01NS117918,R21NS104394,and R21NS119732(to HL)。
文摘Spinal cord injury represents a devastating central nervous system injury that could impair the mobility and sensory function of afflicted patients.The hallmarks of spinal cord injury include neuroinflammation,axonal degeneration,neuronal loss,and reactive gliosis.Furthermore,the formation of a glial scar at the injury site elicits an inhibitory environment for potential neuroregeneration.Besides axonal regeneration,a significant challenge in treating spinal cord injury is to replenish the neurons lost during the pathological process.However,despite decades of research efforts,current strategies including stem cell transplantation have not resulted in a successful clinical therapy.Furthermore,stem cell transplantation faces serious hurdles such as immunorejection of the transplanted cells and ethical issues.In vivo neuronal reprogramming is a recently developed technology and leading a major breakthrough in regenerative medicine.This innovative technology converts endogenous glial cells into functional neurons for injury repair in the central nervous system.The feasibility of in vivo neuronal reprogramming has been demonstrated successfully in models of different neurological disorders including spinal cord injury by numerous laboratories.Several reprogramming factors,mainly the pro-neural transcription factors,have been utilized to reprogram endogenous glial cells into functional neurons with distinct phenotypes.So far,the literature on in vivo neuronal reprogramming in the model of spinal cord injury is still small.In this review,we summarize a limited number of such reports and discuss several questions that we think are important for applying in vivo neuronal reprogramming in the research field of spinal cord injury as well as other central nervous system disorders.
