Amphiphilic cytokine traps remodel marrow adipose tissue for hematopoietic microenvironment amelioration  

作　　者：Shunshu Deng Shuang Zhang Tong Shen Xuanlin Wang Zehua Gao Wenchao Zhang Kai Dai Jing Wang Changsheng Liu 

机构地区：[1]State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai,200237,PR China [2]Institute for Regenerative Medicine,Shanghai East Hospital,Tongji University School of Medicine,Shanghai,200092,PR China [3]Key Laboratory for Ultrafine Materials of the Ministry of Education,East China University of Science and Technology,Shanghai,200237,PR China [4]Engineering Research Center for Biomedical Materials of the Ministry of Education,East China University of Science and Technology,Shanghai,200237,PR China [5]Frontiers Science Center for Materiobiology and Dynamic Chemistry,East China University of Science and Technology,Shanghai,200237,PR China

出　　处：《Bioactive Materials》2024年第12期226-240,共15页生物活性材料（英文）

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);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.

摘　　要：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.

关 键 词：ADIPOCYTES HEMATOPOIESIS In vivo osteo-organoids Stem cell factor Sulfated chitosan Tissue regeneration 

分 类 号：R318[医药卫生—生物医学工程]