title: Specially modified stromal and immune microenvironment in injected bone marrow following intrabone transplantation facilitates allogeneic hematopoietic stem cell engraftment.
abstract: For allogeneic hematopoietic stem cell transplantation (HSCT), the first key step is the engraftment of hematopoietic stem cells (HSCs) across the major histocompatibility complex (MHC) barrier. Intrabone bone marrow transplantation (IBBMT) could replace more recipient stromal cells with donor cells and facilitate allogeneic organ transplantation compared with the conventional intravenous approach. However, it remains unknown whether and how IBBMT reconstructs the immune microenvironment for allogeneic HSCs. We explored where the BM microenvironment changes by determining BM stromal cell chimerism and measuring the change in CXCL-12 expression and regulatory T cells in recipient BM. We found that most stromal cells were replaced by allogeneic cells in the injected BM, with higher expression of immune regulatory cytokines (interleukin-10) compared with the contralateral BM and the intravenous group BM. This difference was independent of injury caused by intrabone injection. Consistent with the microenvironment modification, the allogeneic the engraftment rate and reconstitution capacity of HSCs were enhanced in the injected BM compared with the contralateral BM and intravenous group BM. Surgical removal of the injected bone at 7 days rather than 21 days reduced the levels of allogeneic granulocytes and HSCs in the peripheral blood. In conclusion, IBBMT specially modifies stromal cells in the injected BM which provide immune protective cues that improve the engraftment of allogeneic HSCs in an early period.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhuang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China. Electronic address: xjzxipss@163.com.
authors.forename: Shuzhong
authors.initials: S
authors.lastname: Guo
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D060833:Cellular Microenvironment / Q000276:immunology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D018655:Lymphocyte Count; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: D054377:Chemokine CXCL12