Intraperitoneally infused human mesenchymal stem cells form aggregates with mouse immune cells and attach to peritoneal organs.
Intraperitoneally infused human mesenchymal stem cells form aggregates with mouse immune cells and attach to peritoneal organs.
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DOI：
10.1186/s13287-016-0284-5
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发表时间：
2016-02-10
影响因子：
7.5
通讯作者：
Prockop DJ
中科院分区：
文献类型：
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作者：
Bazhanov N;Ylostalo JH;Bartosh TJ;Tiblow A;Mohammadipoor A;Foskett A;Prockop DJ
间充质干细胞/祖细胞（MSC）在许多疾病模型中显示出有益的作用，部分是通过调节过度的炎症和免疫反应。通常，间充质干细胞的有益作用在其从宿主组织中消失后仍会持续很长时间，这表明间充质干细胞与宿主中的中间细胞相互作用，从而传递或放大其作用。骨髓间充质干细胞通常是静脉注射，但也有报道称，腹腔注射骨髓间充质干细胞也有有益的效果。然而，骨髓间充质干细胞的IP注射的命运尚未得到研究。研究了人骨髓间充质干细胞注射IP后对免疫能力小鼠的影响。利用体内成像技术跟踪腹腔内绿色荧光蛋白标记的间充质干细胞。此外，通过实时人GAPDH mRNA聚合酶链反应测定其在腹膜组织中的滞留。为了描述人间充质干细胞对腹膜免疫系统的影响，我们收集了腹膜灌洗液、大网膜、淋巴结和肠系膜组织。采用流式细胞术评估免疫细胞群，采用实时聚合酶链反应和酶联免疫吸附法检测细胞因子/趋化因子的产生。在给药后3天用脂多糖攻毒来评估免疫系统的预处理。在20分钟内，腹腔灌洗液中不再检测到单个间充质干细胞。相反，它们被恢复为不同大小的聚集体，包含小鼠巨噬细胞和少量B220+淋巴细胞。1天后，大多数含有活骨髓间充质干细胞的聚集体附着在包括网膜和肠系膜在内的整个腹腔部位。在脾脏和空肠淋巴结中检测到的活注射细胞不到0.05%。在所有位置，MSC与小鼠巨噬细胞和B220+淋巴细胞共定位。附着在大网膜和肠系膜上，伴随着免疫细胞的募集和一系列小鼠细胞因子产生的变化。腹腔注射人成纤维细胞后，小鼠细胞因子也出现了类似的增加。IP注射人间充质干细胞后，小鼠巨噬细胞和B220+淋巴细胞迅速形成聚集体，并附着在腹腔壁上。聚集体的形成可能限制了细胞进入体循环。本文的在线版本（doi:10.1186/s13287-016-0284-5）包含补充材料，可供授权用户使用。
Mesenchymal stem/progenitor cells (MSC) have shown beneficial effects in many models of disease in part by modulating excessive inflammatory and immune responses. Frequently the beneficial effects of MSC persist long after their disappearance from host tissues, suggesting that MSC interact with intermediate cells in the host that relay or amplify their effects. The cells have usually been injected intravenously, but beneficial effects have also been reported with intraperitoneal (IP) injection of MSC. However the fate of IP injection of MSC has not been examined. The fate of the human MSC injected IP into immune-competent mice was studied. In vivo imaging was used to track green fluorescent protein-labeled MSC in the peritoneal cavity. In addition, their retention in peritoneal tissues was measured by real-time polymerase chain reaction for human GAPDH mRNA. To describe the effects of human MSC on the immune system of the peritoneum, the peritoneal lavage, omentum, lymph nodes and mesenteric tissues were collected. Flow cytometry was used to evaluate the immune cell populations, while cytokine/chemokine production was measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Challenge with lipopolysaccharide at 3 days after the administration of MSC was used to evaluate the preconditioning of the immune system. Within 20 min, single MSC were no longer detected in peritoneal lavage fluid. Instead they were recovered as aggregates of varying size that contained mouse macrophages and a few B220+ lymphocytes. After 1 day, most of the aggregates containing live MSC were attached to sites throughout the peritoneal cavity including the omentum and mesentery. Less than 0.05 % of the live injected cells were detected in the spleen and jejunal lymph nodes. In all locations, MSC colocalized with mouse macrophages and B220+ lymphocytes. Attachment to the omentum and mesentery was accompanied by the recruitment of immune cells and changes in the production of a series of mouse cytokines. A similar increase in mouse cytokines in the peritoneum was seen after IP injections of human fibroblasts. IP injected human MSC rapidly formed aggregates with mouse macrophages and B220+ lymphocytes and attached to the walls of the peritoneal cavity. The formation of the aggregates probably limits access of the cells to the systemic circulation. The online version of this article (doi:10.1186/s13287-016-0284-5) contains supplementary material, which is available to authorized users.