Mesenchymal stromal cell-derived exosome-rich fractionated secretome confers a hepatoprotective effect in liver injury.
Mesenchymal stromal cell-derived exosome-rich fractionated secretome confers a hepatoprotective effect in liver injury.
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DOI：
10.1186/s13287-017-0752-6
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发表时间：
2018-02-06
影响因子：
7.5
通讯作者：
Kumar A
中科院分区：
文献类型：
--
作者：
Damania A;Jaiman D;Teotia AK;Kumar A
间充质基质细胞（MSCs）在再生医学中是一种很有吸引力的治疗药物。最近，从MSCs的分化到它们在损伤部位的旁分泌作用已经有了一个范式转变。一些报道阐明了MSCs分泌的营养因子在损伤组织修复中的作用。我们假设分离MSC分泌组将丰富含有可溶性生物活性分子的外泌体，提高其治疗肝衰竭的潜力。分离大鼠骨髓间充质干细胞，条件培养基过滤、浓缩、超离心生成分离分泌组。该分泌组的特点是存在外泌体，并在体外肝损伤模型中评估肝损伤的恢复情况。结果在体内得到进一步验证。使用对乙酰氨基酚和过氧化氢进行的体外肝损伤模型研究表明，与未分离的分泌组相比，分离的分泌组存在更好的细胞恢复和降低的细胞毒性。此外，在分离分泌组存在的情况下，细胞显示出氧化应激降低，表明其潜在的抗氧化作用。这些结果在体内肝衰竭模型中得到进一步验证，与未分离分泌组（0.718±0.042）相比，分离分泌组存在时肝脏再生得到改善（0.819±0.035）。提出的工作是一个概念的证明，分离分泌组丰富的某些生物活性分子参与损伤肝组织的修复和恢复。本文在线版本（10.1186/s13287-017-0752-6）包含补充材料，授权用户可获得。
Mesenchymal stromal cells (MSCs) are an attractive therapeutic agent in regenerative medicine. Recently, there has been a paradigm shift from differentiation of MSCs to their paracrine effects at the injury site. Several reports elucidate the role of trophic factors secreted by MSCs toward the repair of injured tissues. We hypothesize that fractionating the MSC secretome will enrich exosomes containing soluble bioactive molecules, improving its therapeutic potential for liver failure. Rat bone marrow MSCs were isolated and the conditioned media filtered, concentrated and ultracentrifuged to generate fractionated secretome. This secretome was characterized for the presence of exosomes and recovery from liver injury assessed in in-vitro liver injury models. The results were further validated in vivo. Studies on in-vitro liver injury models using acetaminophen and hydrogen peroxide show better cell recovery and reduced cytotoxicity in the presence of fractionated as opposed to unfractionated secretome. Further, the cells showed reduced oxidative stress in the presence of fractionated secretome, suggesting a potential antioxidative effect. These results were further validated in vivo in liver failure models, wherein improved liver regeneration in the presence of fractionated secretome (0.819 ± 0.035) was observed as compared to unfractionated secretome (0.718 ± 0.042). The work presented is a proof of concept that fractionating the secretome enriches certain bioactive molecules involved in the repair and recovery of injured liver tissue. Exosome enriched mesenchymal stromal cell-derived fractionated secretome potentiates recovery upon injection in injured liver The online version of this article (10.1186/s13287-017-0752-6) contains supplementary material, which is available to authorized users.
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间充质干细胞参与治疗肝脏疾病的多种功能。
影响因子：
5.3
作者：
Liu WH;Song FQ;Ren LN;Guo WQ;Wang T;Feng YX;Tang LJ;Li K
通讯作者：
Li K
影响因子：
8
作者：
Choudhury ST;Das N;Ghosh S;Ghosh D;Chakraborty S;Ali N
通讯作者：
Ali N
影响因子：
24.5
作者：
Di Bonzo, L. Valfre;Ferrero, I.;Parola, M.
通讯作者：
Parola, M.
影响因子：
1.2
作者：
Arslan, Fatih;Lai, Ruenn Chai;de Kleijn, Dominique P.
通讯作者：
de Kleijn, Dominique P.
DOI：
10.1007/978-3-319-15539-5_7
发表时间：
2015-01-01
期刊：
STUDIES ON HEPATIC DISORDERS
影响因子：
--
作者：
Garcia-Ruiz, Carmen;Morales, Albert;Fernandez-Checa, Jose C.
通讯作者：
Fernandez-Checa, Jose C.