Pain and lifestyle changes are common consequences of intervertebral disc degeneration(IVDD)and affect a large part of the aging population.The stemness of cells is exploited in the field of regenerative medicine as k...Pain and lifestyle changes are common consequences of intervertebral disc degeneration(IVDD)and affect a large part of the aging population.The stemness of cells is exploited in the field of regenerative medicine as key to treat degenerative diseases.Transplanted cells however often face delivery and survival challenges,especially in tissues with a naturally harsh microniche environment such as the intervertebral disc.Recent interest in the secretome of stem cells,especially cargo protected from microniche-related decay as frequently present in degenerating tissues,provides new means of rejuvenating ailing cells and tissues.Exosomes,a type of extracellular vesicles with purposeful cargo gained particular interest in conveying stem cell related attributes of rejuvenation,which will be discussed here in the context of IVDD.展开更多
Regeneration of Intervertebral disc(IVD)is a scientific challenge because of the complex structure and composition of tissue,as well as the difficulty in achieving bionic function.Here,an anatomically correct IVD scaf...Regeneration of Intervertebral disc(IVD)is a scientific challenge because of the complex structure and composition of tissue,as well as the difficulty in achieving bionic function.Here,an anatomically correct IVD scaffold composed of biomaterials,cells,and growth factors were fabricated via three-dimensional(3D)bioprinting technology.Connective tissue growth factor(CTGF)and transforming growth factor-β3(TGF-β3)were loaded onto polydopamine nanoparticles,which were mixed with bone marrow mesenchymal stem cells(BMSCs)for regenerating and simulating the structure and function of the nucleus pulposus and annular fibrosus.In vitro experiments confirmed that CTGF and TGF-β3 could be released from the IVD scaffold in a spatially controlled manner,and induced the corresponding BMSCs to differentiate into nucleus pulposus like cells and annulus fibrosus like cells.Next,the fabricated IVD scaffold was implanted into the dorsum subcutaneous of nude mice.The reconstructed IVD exhibited a zone-specific matrix that displayed the corresponding histological and immunological phenotypes:primarily type II collagen and glycosaminoglycan in the core zone,and type I collagen in the surrounding zone.The testing results demonstrated that it exhibited good biomechanical function of the reconstructed IVD.The results presented herein reveal the clinical application potential of the dual growth factors-releasing IVD scaffold fabricated via 3D bioprinting.However,the evaluation in large mammal animal models needs to be further studied.展开更多
The intervertebral disc(IVD)comprises a gelatinous inner core(nucleus pulposus;NP)and concentric rings(annulus fibrosus;AF).The NP,an important structure for shock absorption in the vertebrate spinal motion segment,ca...The intervertebral disc(IVD)comprises a gelatinous inner core(nucleus pulposus;NP)and concentric rings(annulus fibrosus;AF).The NP,an important structure for shock absorption in the vertebrate spinal motion segment,can be traced back to the notochord in ontogenetic lineage.In vertebrates,the notochord undergoes mucinoid changes,and had been considered vestigial until recently.However,observed correlations between IVD degeneration and back pain in humans have renewed interest in the IVD in biomedical fields.Beyond its mechanical contribution to development,the notochord is also an essential signaling center,which coordinates formation of the neural tube and somites.The pertinent signaling molecules,particularly TGF-b and bone morphogenetic proteins(BMPs),continue to play roles in the adult tissues and have been utilized for tissue regeneration.Genetic factors are major determinants of who will develop IVD degeneration and related back pain,and seem to correlate better with disc degeneration and back pain than do external forces on the spine.In summary,the spinal column is a landmark development in evolution.Genes directing the development of the IVD may also contribute to its maintenance,degeneration,and regeneration.Likewise,structural genes as well as genes responsible for maintenance of the structure are related to IVD degeneration.Finally,genes responsible for inflammation may play a dual role in exacerbating degeneration or facilitating repair responses depending on the context.展开更多
基金supported by the Bayard and Virginia Clarkson Endowment Fund and NIH HD099588 both granted to Thomas Lufkin.
文摘Pain and lifestyle changes are common consequences of intervertebral disc degeneration(IVDD)and affect a large part of the aging population.The stemness of cells is exploited in the field of regenerative medicine as key to treat degenerative diseases.Transplanted cells however often face delivery and survival challenges,especially in tissues with a naturally harsh microniche environment such as the intervertebral disc.Recent interest in the secretome of stem cells,especially cargo protected from microniche-related decay as frequently present in degenerating tissues,provides new means of rejuvenating ailing cells and tissues.Exosomes,a type of extracellular vesicles with purposeful cargo gained particular interest in conveying stem cell related attributes of rejuvenation,which will be discussed here in the context of IVDD.
基金supported by National Key R&D Program of China(No.2018YFB1105600,No.2018YFA0703000)National Natural Science Foundation of China(No.81802131)Project funded by China Postdoctoral Science Foundation(No.2019T120347)and the fund of No.XK2019013.
文摘Regeneration of Intervertebral disc(IVD)is a scientific challenge because of the complex structure and composition of tissue,as well as the difficulty in achieving bionic function.Here,an anatomically correct IVD scaffold composed of biomaterials,cells,and growth factors were fabricated via three-dimensional(3D)bioprinting technology.Connective tissue growth factor(CTGF)and transforming growth factor-β3(TGF-β3)were loaded onto polydopamine nanoparticles,which were mixed with bone marrow mesenchymal stem cells(BMSCs)for regenerating and simulating the structure and function of the nucleus pulposus and annular fibrosus.In vitro experiments confirmed that CTGF and TGF-β3 could be released from the IVD scaffold in a spatially controlled manner,and induced the corresponding BMSCs to differentiate into nucleus pulposus like cells and annulus fibrosus like cells.Next,the fabricated IVD scaffold was implanted into the dorsum subcutaneous of nude mice.The reconstructed IVD exhibited a zone-specific matrix that displayed the corresponding histological and immunological phenotypes:primarily type II collagen and glycosaminoglycan in the core zone,and type I collagen in the surrounding zone.The testing results demonstrated that it exhibited good biomechanical function of the reconstructed IVD.The results presented herein reveal the clinical application potential of the dual growth factors-releasing IVD scaffold fabricated via 3D bioprinting.However,the evaluation in large mammal animal models needs to be further studied.
基金Jason W.Ashley,PhD is supported by the University of Pennsylvania Postdoctoral Opportunities in Research and Teaching(PENN-PORT)fellowship funded by the National Institute of General Medical Sciences Institutional Research and Career Development Award(IRACDA5 K12 GM081259-09)+2 种基金Yejia Zhang,MD,PhD has been supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development(NICHD,1K08 HD049598)This work is supported,in part,by research grants from the Department of Veterans Affairs(VA RR&D I01 RX001321 and VA1I21RX001896)the Research Grants Committee of Hong Kong(T-12-708/12N).
文摘The intervertebral disc(IVD)comprises a gelatinous inner core(nucleus pulposus;NP)and concentric rings(annulus fibrosus;AF).The NP,an important structure for shock absorption in the vertebrate spinal motion segment,can be traced back to the notochord in ontogenetic lineage.In vertebrates,the notochord undergoes mucinoid changes,and had been considered vestigial until recently.However,observed correlations between IVD degeneration and back pain in humans have renewed interest in the IVD in biomedical fields.Beyond its mechanical contribution to development,the notochord is also an essential signaling center,which coordinates formation of the neural tube and somites.The pertinent signaling molecules,particularly TGF-b and bone morphogenetic proteins(BMPs),continue to play roles in the adult tissues and have been utilized for tissue regeneration.Genetic factors are major determinants of who will develop IVD degeneration and related back pain,and seem to correlate better with disc degeneration and back pain than do external forces on the spine.In summary,the spinal column is a landmark development in evolution.Genes directing the development of the IVD may also contribute to its maintenance,degeneration,and regeneration.Likewise,structural genes as well as genes responsible for maintenance of the structure are related to IVD degeneration.Finally,genes responsible for inflammation may play a dual role in exacerbating degeneration or facilitating repair responses depending on the context.
