A comparison of adipose and bone marrow-derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation.

A comparison of adipose and bone marrow-derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation.
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DOI:
10.1186/1476-9255-11-1
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发表时间:
2014-01-07
期刊:
Journal of inflammation (London, England)
影响因子:
--
通讯作者:
Parekkadan B
Parekkadan B
中科院分区:
其他
文献类型:
--
作者:
Elman JS;Li M;Wang F;Gimble JM;Parekkadan B

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骨髓间充质干细胞(BMSCs)是一种在炎症性疾病治疗中具有广泛应用前景的细胞。BMSC释放的分泌因子在几种临床前模型中负责炎症的消退。新的研究发现,脂肪组织也是多能非造血干细胞的储存库,称为脂肪源性基质/干细胞(ASC),具有BMSC的许多共同特征。我们假设ASC和BMSC分泌因子在全身炎症的情况下会产生相当的益处。条件培养基的蛋白质组学分析显示,BMSCs表达显著更高水平的sVEGFR1和sTNFR1,这两种可溶性细胞因子受体在脓毒症中具有已知的治疗活性。在小鼠内毒素诱导的炎症的预防性研究中,我们观察到BMSC分泌的因子与ASC相比提供了更大的内毒素血症小鼠的存活益处和组织保护。sVEGFR1和sTNFR1的中和并没有显著影响用BMSC分泌因子处理的小鼠所经历的存活益处。我们的研究结果表明,骨髓间充质干细胞可能是更有效的细胞治疗用于内毒素休克和ASCs可以定位为免疫调节性疾病的继续探索。可溶性细胞因子受体可以区分不同组织来源的基质细胞,尽管它们可能不是BMSC治疗益处的唯一贡献者。此外,本研究中未讨论的其他分泌因子也可能使这些基质细胞群彼此区分。
Bone marrow-derived mesenchymal stromal cells (BMSCs) are a cell population of intense exploration for therapeutic use in inflammatory diseases. Secreted factors released by BMSCs are responsible for the resolution of inflammation in several pre-clinical models. New studies have uncovered that adipose tissue also serves as a reservoir of multipotent, non-hematopoietic stem cells, termed adipose-derived stromal/stem cells (ASCs), with many common characteristics to BMSCs. We hypothesized that ASC and BMSC secreted factors would lead to a comparable benefit in the context of generalized inflammation. Proteomic profiling of conditioned media revealed that BMSCs express significantly higher levels of sVEGFR1 and sTNFR1, two soluble cytokine receptors with known therapeutic activity in sepsis. In a prophylactic study of endotoxin-induced inflammation in mice, we observed that BMSC secreted factors provided a greater survival benefit and tissue protection of endotoxemic mice compared to ASCs. Neutralization of sVEGFR1 and sTNFR1 did not significantly affect the survival benefit experienced by mice treated with BMSC secreted factors. Our findings suggest that BMSCs may be more effective as a cell therapeutic for use in endotoxic shock and that ASCs may be positioned for continued exploration in immunomodulatory diseases. Soluble cytokine receptors can distinguish stromal cells from different tissue origins, though they may not be the sole contributors to the therapeutic benefit of BMSCs. Furthermore, other secreted factors not discussed in this study may also differentiate these stromal cell populations from one another.
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