Identification of the active components in Bone Marrow Soup: a mitigator against irradiation-injury to salivary glands.
Identification of the active components in Bone Marrow Soup: a mitigator against irradiation-injury to salivary glands.
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DOI：
10.1038/srep16017
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发表时间：
2015-11-03
影响因子：
4.6
通讯作者：
Tran SD
中科院分区：
文献类型：
--
作者：
Fang D;Hu S;Liu Y;Quan VH;Seuntjens J;Tran SD
在单独的研究中，据报道，从整个骨髓细胞中提取的可溶性细胞内内容物，称为“骨髓（BM）汤”，可以分别改善心肌梗塞或放射（IR）后的心脏或唾液功能。然而，BM汤的活性成分尚不清楚。为了证明蛋白质是活性成分，我们设计了一种使用蛋白酶 K 并加热使蛋白质失活并安全注射到小鼠体内的方法。 BM Soup 和“失活的 BM Soup”被注射到唾液腺因 15Gy IR 损伤的小鼠体内。对照小鼠接受盐水注射或不接受IR。 IR 后第 8 周的结果显示，“失活的 BM 汤”并不比注射生理盐水更好，而注射天然 BM 汤可以恢复唾液流动，保护唾液细胞和血管免受 IR 损伤。蛋白芯片检测到BM汤中多种血管生成相关因子（CD26、FGF、HGF、MMP-8、MMP-9、OPN、PF4、SDF-1）和细胞因子（IL-1ra、IL-16）。总之，天然蛋白质（而不是核酸、脂质或碳水化合物）是 IR 后唾液功能恢复的骨汤治疗成分。这种分子治疗方法具有临床潜力，因为理论上它比细胞疗法的致瘤性和免疫原性更低。
In separate studies, an extract of soluble intracellular contents from whole bone marrow cells, named “Bone Marrow (BM) Soup”, was reported to either improve cardiac or salivary functions post-myocardial infarction or irradiation (IR), respectively. However, the active components in BM Soup are unknown. To demonstrate that proteins were the active ingredients, we devised a method using proteinase K followed by heating to deactivate proteins and for safe injections into mice. BM Soup and “deactivated BM Soup” were injected into mice that had their salivary glands injured with 15Gy IR. Control mice received either injections of saline or were not IR. Results at week 8 post-IR showed the ‘deactivated BM Soup’ was no better than injections of saline, while injections of native BM Soup restored saliva flow, protected salivary cells and blood vessels from IR-damage. Protein arrays detected several angiogenesis-related factors (CD26, FGF, HGF, MMP-8, MMP-9, OPN, PF4, SDF-1) and cytokines (IL-1ra, IL-16) in BM Soup. In conclusion, the native proteins (but not the nucleic acids, lipids or carbohydrates) were the therapeutic ingredients in BM Soup for functional salivary restoration following IR. This molecular therapy approach has clinical potential because it is theoretically less tumorigenic and immunogenic than cell therapies.