Hematopoietic stem cell transplantation(HSCT)is extensively employed in the treatment of hematological malignancies but is markedly constrained by the paucity of hematopoietic stem/progenitor cells(HSPCs).Recent studi...Hematopoietic stem cell transplantation(HSCT)is extensively employed in the treatment of hematological malignancies but is markedly constrained by the paucity of hematopoietic stem/progenitor cells(HSPCs).Recent studies have found that marrow adipose tissue(MAT)acts on hematopoiesis through complicated mechanisms.Therefore,the osteo-organoids fabricated in vivo using biomaterials loaded with recombinant human bone morphogenetic protein 2(rhBMP-2)have been used as models of MAT for our research.To obtain sufficient amounts of therapeutic HSPCs and healthy MAT,we have developed amphiphilic chitosan(AC)-gelatin as carriers of rhBMP-2 to the regulate type conversion of adipose tissue and trap hematopoietic growth factors.Unlike medicine interventions or cell therapies,the traps based on AC not only attenuate the occupancy of adipocytes within the hematopoietic microenvironment while preserving stem cell factor concentrations,but also improve marrow metabolism by promoting MAT browning.In conclusion,this approach increases the proportion of HSPCs in osteo-organoids,and optimizes the composition and metabolic status of MAT.These findings furnish an experimental basis for regulating hematopoiesis in vivo through materials that promote the development of autologous HSPCs.Additionally,this approach presents a theoretical model of rapid adipogenesis for the study of adipose-related pathologies and potential pharmacological targets.展开更多
基金supported by the Basic Science Center Program of National Natural Science Foundation of China(No.T2288102)the Key Program of the National Natural Science Foundation of China(No.32230059)+5 种基金the National Natural Science Foundation of China(No.32301123)the Foundation of Frontiers Science Center for Materiobiology and Dynamic Chemistry(No.JKVD1211002)the Wego Project of Chinese Academy of Sciences[No.(2020)005]the China Postdoctoral Science Foundation(No.2022M721147)the Project of National Facility for Translational Medicine(Shanghai)(No.TMSK-2021-134)the Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai.
文摘Hematopoietic stem cell transplantation(HSCT)is extensively employed in the treatment of hematological malignancies but is markedly constrained by the paucity of hematopoietic stem/progenitor cells(HSPCs).Recent studies have found that marrow adipose tissue(MAT)acts on hematopoiesis through complicated mechanisms.Therefore,the osteo-organoids fabricated in vivo using biomaterials loaded with recombinant human bone morphogenetic protein 2(rhBMP-2)have been used as models of MAT for our research.To obtain sufficient amounts of therapeutic HSPCs and healthy MAT,we have developed amphiphilic chitosan(AC)-gelatin as carriers of rhBMP-2 to the regulate type conversion of adipose tissue and trap hematopoietic growth factors.Unlike medicine interventions or cell therapies,the traps based on AC not only attenuate the occupancy of adipocytes within the hematopoietic microenvironment while preserving stem cell factor concentrations,but also improve marrow metabolism by promoting MAT browning.In conclusion,this approach increases the proportion of HSPCs in osteo-organoids,and optimizes the composition and metabolic status of MAT.These findings furnish an experimental basis for regulating hematopoiesis in vivo through materials that promote the development of autologous HSPCs.Additionally,this approach presents a theoretical model of rapid adipogenesis for the study of adipose-related pathologies and potential pharmacological targets.
