Tissue specificity,a key factor in the decellularized tissue matrix(DTM),has shown bioactive functionalities in tuning cell fate-e.g.,the differentiation of mesenchymal stem cells.Notably,cell fate is also determined ...Tissue specificity,a key factor in the decellularized tissue matrix(DTM),has shown bioactive functionalities in tuning cell fate-e.g.,the differentiation of mesenchymal stem cells.Notably,cell fate is also determined by the living microenvironment,including material composition and spatial characteristics.Herein,two neighboring tissues within intervertebral discs,the nucleus pulposus(NP)and annulus fibrosus(AF),were carefully processed into DTM hydrogels(abbreviated DNP-G and DAF-G,respectively)to determine the tissue-specific effects on stem cell fate,such as specific components and different culturing methods,as well as in vivo regeneration.Distinct differences in their protein compositions were identified by proteomic analysis.Interestingly,the fate of human bone marrow mesenchymal stem cells(hBMSCs)also responds to both culturing methods and composition.Generally,hBMSCs cultured with DNP-G(3D)differentiated into NP-like cells,while hBMSCs cultured with DAF-G(2D)underwent AF-like differentiation,indicating a close correlation with the native microenvironments of NP and AF cells,respectively.Furthermore,we found that the integrin-mediated RhoA/LATS/YAP1 signaling pathway was activated in DAF-G(2D)-induced AF-specific differentiation.Additionally,the activation of YAP1 determined the tendency of NP-or AF-specific differentiation and played opposite regulatory effects.Finally,DNP-G and DAF-G specifically promoted tissue regeneration in NP degeneration and AF defect rat models,respectively.In conclusion,DNP-G and DAF-G can specifically determine the fate of stem cells through the integrin-mediated RhoA/LATS/YAP1 signaling pathway,and this tissue specificity is both compositional and spatial,supporting the utilization of tissue-specific DTM in advanced treatments of intervertebral disc degeneration.展开更多
Low back pain is a vital musculoskeletal disease that impairs life quality,leads to disability and imposes heavy economic burden on the society,while it is greatly attributed to intervertebral disc degeneration(IDD).H...Low back pain is a vital musculoskeletal disease that impairs life quality,leads to disability and imposes heavy economic burden on the society,while it is greatly attributed to intervertebral disc degeneration(IDD).However,the existing treatments,such as medicines,chiropractic adjustments and surgery,cannot achieve ideal disc regeneration.Therefore,advanced bioactive therapies are implemented,including stem cells delivery,bioreagents administration,and implantation of biomaterials etc.Among these researches,few reported unsatisfying regenerative outcomes.However,these advanced therapies have barely achieved successful clinical translation.The main reason for the inconsistency between satisfying preclinical results and poor clinical translation may largely rely on the animal models that cannot actually simulate the human disc degeneration.The inappropriate animal model also leads to difficulties in comparing the efficacies among biomaterials in different reaches.Therefore,animal models that better simulate the clinical charateristics of human IDD should be acknowledged.In addition,in vivo regenerative outcomes should be carefully evaluated to obtain robust results.Nevertheless,many researches neglect certain critical characteristics,such as adhesive properties for biomaterials blocking annulus fibrosus defects and hyperalgesia that is closely related to the clinical manifestations,e.g,low back pain.Herein,in this review,we summarized the animal models established for IDD,and highlighted the proper models and parameters that may result in acknowledged IDD models.Then,we discussed the existing biomaterials for disc regeneration and the characteristics that should be considered for regenerating different parts of discs.Finally,well-established assays and parameters for in vivo disc regeneration are explored.展开更多
The authors regret missing out the below change in the acknowledgment section of the article.The original sentence reads as"This work was supported by the Major Research Plan of National Natural Science Foundatio...The authors regret missing out the below change in the acknowledgment section of the article.The original sentence reads as"This work was supported by the Major Research Plan of National Natural Science Foundation of China[No.91649204],the National Key Research and Development Program of China[2016YFC1100100],…"and the same has been corrected to"This work was supported by the National Key Research and Development Program of China[2016YFC1100100],the Major Research Plan of National Natural Science Foundation of China[No.91649204],…"and the same has been corrected to"This work was supported by the National Key Research and Development Program of China[2016YFC1100100],the Major Research Plan of National Natural Science Foundation of China[No.91649204],…".展开更多
基金This work was supported by the Major Research Plan of National Natural Science Foundation of China[No.91649204]the National Key Research and Development Program of China[2016YFC1100100]the Scientific Research Training Program for Young Talents from Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,National Natural Science Foundation of China(82002333)。
文摘Tissue specificity,a key factor in the decellularized tissue matrix(DTM),has shown bioactive functionalities in tuning cell fate-e.g.,the differentiation of mesenchymal stem cells.Notably,cell fate is also determined by the living microenvironment,including material composition and spatial characteristics.Herein,two neighboring tissues within intervertebral discs,the nucleus pulposus(NP)and annulus fibrosus(AF),were carefully processed into DTM hydrogels(abbreviated DNP-G and DAF-G,respectively)to determine the tissue-specific effects on stem cell fate,such as specific components and different culturing methods,as well as in vivo regeneration.Distinct differences in their protein compositions were identified by proteomic analysis.Interestingly,the fate of human bone marrow mesenchymal stem cells(hBMSCs)also responds to both culturing methods and composition.Generally,hBMSCs cultured with DNP-G(3D)differentiated into NP-like cells,while hBMSCs cultured with DAF-G(2D)underwent AF-like differentiation,indicating a close correlation with the native microenvironments of NP and AF cells,respectively.Furthermore,we found that the integrin-mediated RhoA/LATS/YAP1 signaling pathway was activated in DAF-G(2D)-induced AF-specific differentiation.Additionally,the activation of YAP1 determined the tendency of NP-or AF-specific differentiation and played opposite regulatory effects.Finally,DNP-G and DAF-G specifically promoted tissue regeneration in NP degeneration and AF defect rat models,respectively.In conclusion,DNP-G and DAF-G can specifically determine the fate of stem cells through the integrin-mediated RhoA/LATS/YAP1 signaling pathway,and this tissue specificity is both compositional and spatial,supporting the utilization of tissue-specific DTM in advanced treatments of intervertebral disc degeneration.
基金supported by the Major Research Plan of National Natural Science Foundation of China(No.91649204)the National Key Research and Development Program of China(No.2016YFC1100100)+2 种基金the National Natural Science Foundation of China(No.81974352)the Scientific Research Training Program for Young Talents from Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,National Natural Science Foundation of China(No.82002333)Zhejiang Provincial Natural Science Foundation of China(No.LQ21H060004).
文摘Low back pain is a vital musculoskeletal disease that impairs life quality,leads to disability and imposes heavy economic burden on the society,while it is greatly attributed to intervertebral disc degeneration(IDD).However,the existing treatments,such as medicines,chiropractic adjustments and surgery,cannot achieve ideal disc regeneration.Therefore,advanced bioactive therapies are implemented,including stem cells delivery,bioreagents administration,and implantation of biomaterials etc.Among these researches,few reported unsatisfying regenerative outcomes.However,these advanced therapies have barely achieved successful clinical translation.The main reason for the inconsistency between satisfying preclinical results and poor clinical translation may largely rely on the animal models that cannot actually simulate the human disc degeneration.The inappropriate animal model also leads to difficulties in comparing the efficacies among biomaterials in different reaches.Therefore,animal models that better simulate the clinical charateristics of human IDD should be acknowledged.In addition,in vivo regenerative outcomes should be carefully evaluated to obtain robust results.Nevertheless,many researches neglect certain critical characteristics,such as adhesive properties for biomaterials blocking annulus fibrosus defects and hyperalgesia that is closely related to the clinical manifestations,e.g,low back pain.Herein,in this review,we summarized the animal models established for IDD,and highlighted the proper models and parameters that may result in acknowledged IDD models.Then,we discussed the existing biomaterials for disc regeneration and the characteristics that should be considered for regenerating different parts of discs.Finally,well-established assays and parameters for in vivo disc regeneration are explored.
文摘The authors regret missing out the below change in the acknowledgment section of the article.The original sentence reads as"This work was supported by the Major Research Plan of National Natural Science Foundation of China[No.91649204],the National Key Research and Development Program of China[2016YFC1100100],…"and the same has been corrected to"This work was supported by the National Key Research and Development Program of China[2016YFC1100100],the Major Research Plan of National Natural Science Foundation of China[No.91649204],…"and the same has been corrected to"This work was supported by the National Key Research and Development Program of China[2016YFC1100100],the Major Research Plan of National Natural Science Foundation of China[No.91649204],…".
