Altered protein secretions during interactions between adipose tissue- or bone marrow-derived stromal cells and inflammatory cells.
Altered protein secretions during interactions between adipose tissue- or bone marrow-derived stromal cells and inflammatory cells.
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DOI：
10.1186/s13287-015-0052-y
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发表时间：
2015-04-16
影响因子：
7.5
通讯作者：
Ishihara M
中科院分区：
文献类型：
--
作者：
Hattori H;Ishihara M
旁分泌效应可以在基于细胞的疗法中利用，所述疗法分泌因子，如趋化因子和细胞因子，并且可以将炎性细胞募集到移植物中。在这项研究中，小鼠脂肪组织来源的基质细胞（ASC）和骨髓来源的基质细胞（ST 2细胞）被用来检查旁分泌与炎症细胞相互作用的变化。将绿色荧光蛋白阳性（GFP+）骨髓细胞（BMC）通过股静脉注射到受照射的小鼠中，并将ASC和ST 2细胞皮内移植。随后，使用体内成像系统观察GFP+ BMCs的行为。为了检测迁移到ASC和ST 2细胞移植区域的骨髓源性炎性细胞，使用抗Gr 1、CD 11 c和F4/80的抗体对切片进行免疫染色，并使用酶联免疫吸附测定法检测培养基中的分泌蛋白。许多骨髓源性炎症细胞迁移到ASC和ST 2细胞移植部位。其中，在早期检测到中性粒细胞，在较晚的时间点主要检测到巨噬细胞。许多趋化因子，细胞因子，生长因子，基质金属蛋白酶（MMPs），和金属蛋白酶组织抑制剂（TIMPs）分泌丰富的ASCs，和分泌增加与炎性细胞共培养，除了分泌胰岛素样生长因子-1，MMP-9和MMP-13。虽然ST 2细胞的分泌物少于ASCs，但与炎性细胞共培养使这些分泌物增加到与ASCs相似的水平。然而，与ASC不同，ST 2细胞不分泌血管抑素、MMP-2或MMP-3。最后，ASCs不仅分泌促炎细胞因子、血管生成因子和MMPs，而且还分泌抗炎细胞因子、抗血管生成因子和TIMPs。使用ASC和ST 2细胞的基于细胞的疗法的效果取决于由趋化因子、细胞因子、生长因子、MMP和TIMP介导的旁分泌效应，其包括对移植细胞和炎性细胞之间的相互作用的应答。此外，移植细胞的旁分泌效应受炎性细胞的影响，并通过分泌抑制剂的平衡来调节。本文的在线版本（doi：10.1186/s13287-015-0052-y）包含补充材料，可供授权用户使用。
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. 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. 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. 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. The online version of this article (doi:10.1186/s13287-015-0052-y) contains supplementary material, which is available to authorized users.
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