Secretome of peripheral blood mononuclear cells enhances wound healing.

Secretome of peripheral blood mononuclear cells enhances wound healing.
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DOI:
10.1371/journal.pone.0060103
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Ankersmit HJ
Ankersmit HJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mildner M;Hacker S;Haider T;Gschwandtner M;Werba G;Barresi C;Zimmermann M;Golabi B;Tschachler E;Ankersmit HJ

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无法愈合的皮肤溃疡通常对大多数常见的治疗方法都有抵抗力。使用生长因子治疗已被证明能改善慢性创面的愈合。在这里,我们研究新鲜分离的外周血单个核细胞(PBMC)的冻干培养上清液是否能够促进伤口愈合。制备健康人PBMC,培养24小时。收集上清液,透析,冷冻干燥(SECPBMC)。在C57BL/6J小鼠背部放置6 mm穿刺式活检伤,每天涂抹含乳剂的SECPBMC或对照组,连续3d。H&E染色观察细胞形态变化,CD31免疫组织化学染色分析新生血管形成情况。通过迁移实验、细胞周期分析和成管实验,研究其对不同皮肤细胞的体外作用。Western印迹分析信号转导通路。将SECPBMC应用于6 mm穿孔活组织检查创面,可显著提高创面闭合率。6d后对创面进行H&E染色,结果显示,使用含SECPBMC的乳剂后,创面愈合更快。此外,CD31阳性细胞大量增加,表明新生血管生成增强。在原代培养的人成纤维细胞(FB)和角质形成细胞(KC)中,可诱导其迁移,但不能促进其增殖。在内皮细胞(EC)中,SECPBMC在基质实验中诱导增殖和管状形成。此外,SECPBMC对皮肤细胞的处理导致了参与细胞迁移、增殖和生存的多条信号通路的诱导。综上所述,我们可以证明,含有来自健康人的PBMC分泌体的乳剂可以加速小鼠模型的伤口愈合,并诱导人类原代皮肤细胞的伤口愈合相关机制。因此,这种乳剂的配方和使用可能是治疗无法愈合的皮肤溃疡的一种可能的新选择。
Non-healing skin ulcers are often resistant to most common therapies. Treatment with growth factors has been demonstrated to improve closure of chronic wounds. Here we investigate whether lyophilized culture supernatant of freshly isolated peripheral blood mononuclear cells (PBMC) is able to enhance wound healing. PBMC from healthy human individuals were prepared and cultured for 24 hours. Supernatants were collected, dialyzed and lyophilized (SECPBMC). Six mm punch biopsy wounds were set on the backs of C57BL/6J-mice and SECPBMC containing emulsion or controls were applied daily for three days. Morphology and neo-angiogenesis were analyzed by H&E-staining and CD31 immuno-staining, respectively. In vitro effects on diverse skin cells were investigated by migration assays, cell cycle analysis, and tube formation assay. Signaling pathways were analyzed by Western blot analysis. Application of SECPBMC on 6 mm punch biopsy wounds significantly enhanced wound closure. H&E staining of the wounds after 6 days revealed that wound healing was more advanced after application of SECPBMC containing emulsion. Furthermore, there was a massive increase in CD31 positive cells, indicating enhanced neo-angiogenesis. In primary human fibroblasts (FB) and keratinocytes (KC) migration but not proliferation was induced. In endothelial cells (EC) SECPBMC induced proliferation and tube-formation in a matrigel-assay. In addition, SECPBMC treatment of skin cells led to the induction of multiple signaling pathways involved in cell migration, proliferation and survival. In summary, we could show that emulsions containing the secretome of PBMC derived from healthy individuals accelerates wound healing in a mouse model and induce wound healing associated mechanisms in human primary skin cells. The formulation and use of such emulsions might therefore represent a possible novel option for the treatment of non-healing skin ulcers.
凋亡和心脏内注射凋亡白细胞悬浮液可通过在心肌梗塞后增加心脏疤痕组织中的弹性蛋白表达来防止心室重塑。
DOI: 10.1007/s00395-011-0173-0
发表时间: 2011-06
影响因子: 9.5
作者:
Lichtenauer M;Mildner M;Baumgartner A;Hasun M;Werba G;Beer L;Altmann P;Roth G;Gyöngyösi M;Podesser BK;Ankersmit HJ
通讯作者: Ankersmit HJ
DOI: 10.1161/circresaha.108.192138
发表时间: 2009-05-08
影响因子: 20.1
作者:
Barcelos LS;Duplaa C;Kränkel N;Graiani G;Invernici G;Katare R;Siragusa M;Meloni M;Campesi I;Monica M;Simm A;Campagnolo P;Mangialardi G;Stevanato L;Alessandri G;Emanueli C;Madeddu P
通讯作者: Madeddu P
DOI: 10.1111/j.1365-2362.2009.02111.x
发表时间: 2009-06-01
影响因子: 5.5
作者:
Ankersmit, H. J.;Hoetzenecker, K.;Podesser, B. K.
通讯作者: Podesser, B. K.
DOI: 10.1016/s0950-821x(05)80155-0
发表时间: 1994-05-01
期刊: EUROPEAN JOURNAL OF VASCULAR SURGERY
影响因子: --
作者:
HOLZINGER, C;ZUCKERMANN, A;WOLNER, E
通讯作者: WOLNER, E
DOI: 10.1167/iovs.11-8211
发表时间: 2012-02-01
影响因子: 4.4
作者:
Tasso, Roberta;Ilengo, Cristina;Pennesi, Giuseppina
通讯作者: Pennesi, Giuseppina