Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functiona...Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons in vivo is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold in vitro. Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation. DV-SC formed a targeted connection with the host’s ascending and descending axons, partially restored interrupted neural circuits, and improved motor evoked potentials and the hindlimb function of animals with SCI. This suggests that the transplantation of pre-differentiated hscNPCs with spinal cord dorsal and ventral neuronal characteristics could be a promising strategy for SCI repair.展开更多
Transplantation of adult spinal cord tissue(aSCT)is a promising treatment for spinal cord injury(SCI)basing on various types of neural cells and matrix components inside aSCT.However,long-term systemic administration ...Transplantation of adult spinal cord tissue(aSCT)is a promising treatment for spinal cord injury(SCI)basing on various types of neural cells and matrix components inside aSCT.However,long-term systemic administration of immunosuppressors(e.g.tacrolimus,TAC)is required for the survival of allogeneic tissue,which often associated with severe side effects such as infection,liver damageand renal failure.In this study,a triglycerol monostearate(TGM)-based TAC delivery system(e.g.TAC@TGM)with high drug loading concentration was developed,which possessed injectable properties as well as sustainable and immune-responsive drug release behaviors.In complete transected SCI model,locally injected TAC@TGM could reduce the infiltration of inflammation cells,enhance the survival of transplanted aSCT(e.g.Tuj-1^(+)and NF^(+)neurons)and promote the recovery of locomotor function.Moreover,controlled release of TAC by TAC@TGM attenuated side effects of TAC on liver and kidneys compared with traditional systemic administration.More importantly,the developed TAC@TGM system provided a facile single dose of long-term immunosuppressive effect not just for aSCT transplantation,but also for other tissue/organ and cell transplantations.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81891002)the Strategic Priority Research Program of the Chinese Academy of Sciences(,XDA16040702 XDA16040704)+2 种基金Youth Innovation Promotion Association CAS(Grant No.Y202031)We also thanked the support from CAS Project for Young Scientists in Basic Research(Grant No.YSBR073)the Key Research and Development Program of Hunan Province(2021DK2003).
文摘Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons in vivo is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold in vitro. Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation. DV-SC formed a targeted connection with the host’s ascending and descending axons, partially restored interrupted neural circuits, and improved motor evoked potentials and the hindlimb function of animals with SCI. This suggests that the transplantation of pre-differentiated hscNPCs with spinal cord dorsal and ventral neuronal characteristics could be a promising strategy for SCI repair.
基金supported by the Key Research and Development Program of Hunan Province(Grant Number 2021DK2003)the National Natural Science Foundation of China(Grant Number 81891000)+1 种基金Fundamental Research Funds of the Central Universities(Grant Number 521119200010)Strategic Priority Research Program of the Chinese Academy of Sciences(Grant Numbers XDA16040601,XDA16040704).
文摘Transplantation of adult spinal cord tissue(aSCT)is a promising treatment for spinal cord injury(SCI)basing on various types of neural cells and matrix components inside aSCT.However,long-term systemic administration of immunosuppressors(e.g.tacrolimus,TAC)is required for the survival of allogeneic tissue,which often associated with severe side effects such as infection,liver damageand renal failure.In this study,a triglycerol monostearate(TGM)-based TAC delivery system(e.g.TAC@TGM)with high drug loading concentration was developed,which possessed injectable properties as well as sustainable and immune-responsive drug release behaviors.In complete transected SCI model,locally injected TAC@TGM could reduce the infiltration of inflammation cells,enhance the survival of transplanted aSCT(e.g.Tuj-1^(+)and NF^(+)neurons)and promote the recovery of locomotor function.Moreover,controlled release of TAC by TAC@TGM attenuated side effects of TAC on liver and kidneys compared with traditional systemic administration.More importantly,the developed TAC@TGM system provided a facile single dose of long-term immunosuppressive effect not just for aSCT transplantation,but also for other tissue/organ and cell transplantations.