RRC ID 45450
著者 Hattori H, Ishihara M.
タイトル Altered protein secretions during interactions between adipose tissue- or bone marrow-derived stromal cells and inflammatory cells.
ジャーナル Stem Cell Res Ther
Abstract INTRODUCTION:Paracrine effects can be exploited in cell-based therapies that secrete factors, such as chemokines and cytokines, and can recruit inflammatory cells to transplants. In this study, mouse adipose tissue-derived stromal cells (ASCs) and bone marrow-derived stromal cells (ST2 cells) were used to examine changes in paracrine interactions with inflammation cells.
METHODS:Green fluorescent protein positive (GFP+) bone marrow cells (BMCs) were injected into an irradiated mouse via the femoral vein, and ASCs and ST2 cells were transplanted intradermally. Subsequently, an in vivo imaging system was used to observe behaviors of GFP+ BMCs. To detect bone marrow-derived inflammatory cells which migrated to the ASC and ST2 cell transplantation area, the sections were immunostained using antibodies against Gr1, CD11c, and F4/80, and secretory proteins were detected in culture medium using enzyme-linked immunosorbent assay.
RESULTS:Many bone marrow-derived inflammatory cells migrated to ASC and ST2 cell transplantation sites. Among these, neutrophils were detected during the early period and macrophages were predominantly detected at a later point in time. Many chemokines, cytokines, growth factors, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) were secreted in abundance from ASCs, and the secretion increased by co-culturing with inflammatory cells, except for secretions of insulin-like growth factor-1, MMP-9 and MMP-13. Although secretions from ST2 cells were less than those from ASCs, co-culture with inflammatory cells increased these secretions to levels similar to those of ASCs. However, unlike ASCs, the ST2 cells did not secrete angiostatin, MMP-2, or MMP-3. Finally, ASCs secreted not only proinflammatory cytokines, angiogenic factors and MMPs but also anti-inflammatory cytokines, anti-angiogenesis factors, and TIMPs.
CONCLUSIONS:The effects of cell-based therapies using ASCs and ST2 cells are depended on paracrine effects that are mediated by chemokines, cytokines, growth factors, MMPs, and TIMPs, which comprise responses to interactions between transplanted cells and inflammatory cells. Moreover, paracrine effects of transplanted cells are influenced by inflammatory cells, and are moderated by a balance of secreted inhibitors.
巻・号 6(1)
ページ 70
公開日 2015-4-16
DOI 10.1186/s13287-015-0052-y
PII 10.1186/s13287-015-0052-y
PMID 25884474
PMC PMC4417284
MeSH Adipose Tissue / cytology* Animals Biomarkers / metabolism Bone Marrow Cells / cytology* Cell Movement Cell Proliferation Cells, Cultured Cytokines / metabolism Inflammation / immunology* Intercellular Signaling Peptides and Proteins / metabolism Macrophages / immunology Male Matrix Metalloproteinases / metabolism Mesenchymal Stem Cell Transplantation Mesenchymal Stem Cells / metabolism* Mice Mice, Inbred C57BL Neovascularization, Physiologic / physiology Neutrophils / immunology Paracrine Communication / physiology* Tissue Inhibitor of Metalloproteinases / metabolism Wound Healing / physiology
IF 5.116
引用数 13
WOS 分野 MEDICINE, RESEARCH & EXPERIMENTAL CELL BIOLOGY
リソース情報
ヒト・動物細胞 ST2(RCB0224)