Autologous bone marrow-derived mesenchymal stem cells(BMSCs)have been shown to promote osteogenesis;however,the effects of allogeneic BMSCs(allo-BMSCs)on bone regeneration remain unclear.Therefore,we explored the bone...Autologous bone marrow-derived mesenchymal stem cells(BMSCs)have been shown to promote osteogenesis;however,the effects of allogeneic BMSCs(allo-BMSCs)on bone regeneration remain unclear.Therefore,we explored the bone regeneration promotion effect of allo-BMSCs in 3D-printed autologous bone particle(ABP)scaffolds.First,we concurrently printed scaffolds with polycaprolactone,ABPs,and allo-BMSCs for appropriate support,providing bioactive factors and seed cells to promote osteogenesis.In vitro studies showed that ABP scaffolds promoted allo-BMSC osteogenic differentiation.In vivo studies revealed that the implantation of scaffolds loaded with ABPs and allo-BMSCs into canine skull defects for nine months promoted osteogenesis.Further experiments suggested that only a small portion of implanted allo-BMSCs survived and differentiated into vascular endothelial cells,chondrocytes,and osteocytes.The implanted allo-BMSCs released stromal cell-derived factor 1 through paracrine signaling to recruit native BMSCs into the defect,promoting bone regeneration.This study contributes to our understanding of allo-BMSCs,providing information relevant to their future application.展开更多
GUoblastoma multiforme （GBM） is a highly invasive brain tumor with limited therapeutic means and poor prognosis. Recent stud- ies indicate that glioma-initiating ceUs/gUoma stem ceils （GICs/GSCs） may be responsibl...GUoblastoma multiforme （GBM） is a highly invasive brain tumor with limited therapeutic means and poor prognosis. Recent stud- ies indicate that glioma-initiating ceUs/gUoma stem ceils （GICs/GSCs） may be responsible for tumor initiation, infiltration, and recurrence. GICs could aberrantly employ molecular machinery balancing self-renewal and differentiation of embryonic neural precursors. Here, we find that paired related homeobox 1 （PRRX1）, a homeodomain transcription factor that was previously reported to control skeletal development, is expressed in cortical neural progenitors and is required for their self-renewal and proper differentiation. Further, PRRX1 is overrepresented in gUoma samples and labels GlCs. Gtioma celts and GlCs depleted with PRRX1 could not propagate in vitro or form tumors in the xenograft mouse model. The GIC self-renewal function regulated by PRRX1 is mediated by dopamine D2 receptor （DRD2）. PRRX1 directly binds to the DRD2 promoter and transactivates its expression in GICs. Blockage of the DRD2 signaling hampers GIC self-renewal, whereas its overexpression restores the propagating and tumorigenic potential of PRRXl-depleted GlCs. Finally, PRRX1 potentiates GICs via DRD2-mediated extracetlutar signal-related kinase （ERK） and AKT activation. Thus, our study suggests that therapeutic targeting the PRRX1-DRD2-ERK/AKT axis in GICs is a promising strategy for treating GBMs.展开更多
Astrocytes have potential to break synchrony between neurons. Authors＇ recent researches reveal that astrocytes vary the synchronization threshold and provide an appropriate feedback control in stabilizing neural act...Astrocytes have potential to break synchrony between neurons. Authors＇ recent researches reveal that astrocytes vary the synchronization threshold and provide an appropriate feedback control in stabilizing neural activities. In this study, we propose an astrocyte-inspired controller for desynchronization of two coupled limit-cycle oscillators as a minimal network model. The design procedure consists of two parts. First, based on the astrocyte model, the structure of the dynamic controller is suggested. Then, to have an emcient controller, parameters of controller are tuned through an optimization algo- rithm. The proposed bio-inspired controller takes advantages of three important proper- ties： （1） the controller desynchronizes the oscillators without any undesirable effects （e.g. stopping, annihilating or starting divergent oscillations）; （2） it consumes little effort to preserve the desirable desynchronized state; and （3） the controller is robust with respect to parameters＇ variations. Simulation results reveal the ability of the proposed controller.展开更多
基金supported by the Science and Technology Development Fund of the Fourth Military Medical University(No.2016XB051)the Military Medical Promotion Plan of the Fourth Military Medical University(No.2016TSA-005)+2 种基金the Science and Technology Program of Guangzhou(No.201604040002)the Youth Development Project of Air Force Medical University(No.21QNPY072)the Xijing Hospital Booster Program(No.XJZT24CZ10).
文摘Autologous bone marrow-derived mesenchymal stem cells(BMSCs)have been shown to promote osteogenesis;however,the effects of allogeneic BMSCs(allo-BMSCs)on bone regeneration remain unclear.Therefore,we explored the bone regeneration promotion effect of allo-BMSCs in 3D-printed autologous bone particle(ABP)scaffolds.First,we concurrently printed scaffolds with polycaprolactone,ABPs,and allo-BMSCs for appropriate support,providing bioactive factors and seed cells to promote osteogenesis.In vitro studies showed that ABP scaffolds promoted allo-BMSC osteogenic differentiation.In vivo studies revealed that the implantation of scaffolds loaded with ABPs and allo-BMSCs into canine skull defects for nine months promoted osteogenesis.Further experiments suggested that only a small portion of implanted allo-BMSCs survived and differentiated into vascular endothelial cells,chondrocytes,and osteocytes.The implanted allo-BMSCs released stromal cell-derived factor 1 through paracrine signaling to recruit native BMSCs into the defect,promoting bone regeneration.This study contributes to our understanding of allo-BMSCs,providing information relevant to their future application.
基金This work was supported by grants from the National Natural Science Foundation of China （31671418 and 31471361）, the National Key Basic Research Program of China （2012CB967002）, and Fundamental Research Funds for the Central Universities （2042016kf1020 and 2042017kf0205） to Y.Z. and the NIH grant （HL119478） to 6.D.
文摘GUoblastoma multiforme （GBM） is a highly invasive brain tumor with limited therapeutic means and poor prognosis. Recent stud- ies indicate that glioma-initiating ceUs/gUoma stem ceils （GICs/GSCs） may be responsible for tumor initiation, infiltration, and recurrence. GICs could aberrantly employ molecular machinery balancing self-renewal and differentiation of embryonic neural precursors. Here, we find that paired related homeobox 1 （PRRX1）, a homeodomain transcription factor that was previously reported to control skeletal development, is expressed in cortical neural progenitors and is required for their self-renewal and proper differentiation. Further, PRRX1 is overrepresented in gUoma samples and labels GlCs. Gtioma celts and GlCs depleted with PRRX1 could not propagate in vitro or form tumors in the xenograft mouse model. The GIC self-renewal function regulated by PRRX1 is mediated by dopamine D2 receptor （DRD2）. PRRX1 directly binds to the DRD2 promoter and transactivates its expression in GICs. Blockage of the DRD2 signaling hampers GIC self-renewal, whereas its overexpression restores the propagating and tumorigenic potential of PRRXl-depleted GlCs. Finally, PRRX1 potentiates GICs via DRD2-mediated extracetlutar signal-related kinase （ERK） and AKT activation. Thus, our study suggests that therapeutic targeting the PRRX1-DRD2-ERK/AKT axis in GICs is a promising strategy for treating GBMs.
文摘Astrocytes have potential to break synchrony between neurons. Authors＇ recent researches reveal that astrocytes vary the synchronization threshold and provide an appropriate feedback control in stabilizing neural activities. In this study, we propose an astrocyte-inspired controller for desynchronization of two coupled limit-cycle oscillators as a minimal network model. The design procedure consists of two parts. First, based on the astrocyte model, the structure of the dynamic controller is suggested. Then, to have an emcient controller, parameters of controller are tuned through an optimization algo- rithm. The proposed bio-inspired controller takes advantages of three important proper- ties： （1） the controller desynchronizes the oscillators without any undesirable effects （e.g. stopping, annihilating or starting divergent oscillations）; （2） it consumes little effort to preserve the desirable desynchronized state; and （3） the controller is robust with respect to parameters＇ variations. Simulation results reveal the ability of the proposed controller.
