Rapid tissue regeneration induced by intracellular ATP delivery-A preliminary mechanistic study.
Rapid tissue regeneration induced by intracellular ATP delivery-A preliminary mechanistic study.
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细胞内 ATP 递送诱导的快速组织再生 - 初步机制研究。
DOI：
10.1371/journal.pone.0174899
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Chien S
中科院分区：
文献类型：
--
作者：
Sarojini H;Billeter AT;Eichenberger S;Druen D;Barnett R;Gardner SA;Galbraith NJ;Polk HC Jr;Chien S
我们已经报道了一种新的现象，在急性伤口愈合后使用细胞内ATP输送-非常快速的组织再生，开始手术后不到24小时，并伴随着大量的巨噬细胞运输，原位增殖，和直接的胶原蛋白的生产。这种不寻常的过程绕过了传统的临时细胞外基质的形成，并显着缩短了伤口愈合过程。虽然巨噬细胞/单核细胞已知在伤口愈合的起始和进展中起关键作用，但它们在伤口愈合中的原位增殖和直接胶原产生以前从未报道过。我们已经探索了伤口愈合过程中这两个非常具体的途径，同时通过分析伤口样本和进行体外研究排除了体内环境中的混杂因素。使用免疫组织化学研究能够检测ATP囊泡处理的伤口中原位巨噬细胞增殖。原代人巨噬细胞和Raw 264.7细胞用于体外研究，涉及用ATP囊泡、单独的游离Mg-ATP、单独的脂质囊泡、Regranex或培养基处理。通过ELISA测定培养物上清液的1型胶原α 1、MCP-1、IL-6和IL-10水平。用免疫细胞化学方法检测细胞内1型胶原α1的定位。ATP-囊泡治疗的伤口表现出高的免疫反应性对BrdU和PCNA抗原，表明原位增殖。与用Regranex处理的细胞相比，用ATP囊泡处理的大多数培养的巨噬细胞保持其经典表型，并在更长的时间内表达高水平的1型胶原α1。这些研究提供了伤口愈合过程中原位巨噬细胞增殖和直接胶原蛋白产生的第一个明确证据。这些发现为组织再生非常迅速提供了部分解释，这种治疗可能为急性和慢性伤口护理带来希望。
We have reported a new phenomenon in acute wound healing following the use of intracellular ATP delivery—extremely rapid tissue regeneration, which starts less than 24 h after surgery, and is accompanied by massive macrophage trafficking, in situ proliferation, and direct collagen production. This unusual process bypasses the formation of the traditional provisional extracellular matrix and significantly shortens the wound healing process. Although macrophages/monocytes are known to play a critical role in the initiation and progression of wound healing, their in situ proliferation and direct collagen production in wound healing have never been reported previously. We have explored these two very specific pathways during wound healing, while excluding confounding factors in the in vivo environment by analyzing wound samples and performing in vitro studies. The use of immunohistochemical studies enabled the detection of in situ macrophage proliferation in ATP-vesicle treated wounds. Primary human macrophages and Raw 264.7 cells were used for an in vitro study involving treatment with ATP vesicles, free Mg-ATP alone, lipid vesicles alone, Regranex, or culture medium. Collagen type 1α 1, MCP-1, IL-6, and IL-10 levels were determined by ELISA of the culture supernatant. The intracellular collagen type 1α1 localization was determined with immunocytochemistry. ATP-vesicle treated wounds showed high immunoreactivity towards BrdU and PCNA antigens, indicating in situ proliferation. Most of the cultured macrophages treated with ATP-vesicles maintained their classic phenotype and expressed high levels of collagen type 1α1 for a longer duration than was observed with cells treated with Regranex. These studies provide the first clear evidence of in situ macrophage proliferation and direct collagen production during wound healing. These findings provide part of the explanation for the extremely rapid tissue regeneration, and this treatment may hold promise for acute and chronic wound care.