Mesenchymal stromal cells form vascular tubes when placed in fibrin sealant and accelerate wound healing in vivo.
Mesenchymal stromal cells form vascular tubes when placed in fibrin sealant and accelerate wound healing in vivo.
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DOI：
10.1016/j.biomaterials.2014.11.011
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发表时间：
2015-02
期刊：
影响因子：
14
通讯作者：
Niklason, Laura E.
中科院分区：
文献类型：
--
作者：
Mendez, Julio J.;Ghaedi, Mahboobe;Sivarapatna, Amogh;Dimitrievska, Sashka;Shao, Zhen;Osuji, Chinedum O.;Steinbacher, Derek M.;Leffell, David J.;Niklason, Laura E.
关键词：
不愈合的慢性伤口是一个日益严重的公共卫生问题，可能源于受影响部位的血管生成不足。在这里，我们开发了一种纤维蛋白制剂，允许脂肪来源的间充质基质细胞（ADSC）在体外形成管状结构。管状结构表达内皮标记物，包括CD 31和VE-钙粘蛋白，以及周细胞标记物NG 2。MSC在纤维蛋白凝胶内形成管状结构的能力直接取决于凝血酶和纤维蛋白原的化学计量比和所得的凝胶浓度，以及bFGF的存在。测试硬度不同的弹性凝胶制剂。如PCR、FACS和免疫染色所示，包埋在硬纤维蛋白制剂中的ADSC表达VE-钙粘蛋白和CD 31。共聚焦成像分析表明，管状结构的形成，包含可见的管腔，在体外的硬纤维蛋白凝胶。与较软的凝胶相比，在较硬的凝胶中生长的ADSC分泌的bFGF的量也存在差异。此外，hAT-MSC在皮下注射到小鼠中后产生了VE-钙粘蛋白阳性的可灌注血管，而含有ADSC的较软纤维蛋白制剂则没有。在硬纤维蛋白凝胶中递送的ADSC的应用允许伤口更快地愈合，如通过伤口大小、肉芽组织的量和胶原蛋白含量所评估的。有趣的是，在愈合5天后，ADSC保留在纤维蛋白凝胶内，并且没有整合到体内愈合伤口的肉芽组织中。这些数据显示，与未处理或用缺乏ADSC的纤维蛋白凝胶处理的伤口相比，ADSC能够在纤维蛋白凝胶内形成管状结构，并且还可能有助于更快的伤口愈合。
Non-healing, chronic wounds are a growing public health problem and may stem from insufficient angiogenesis in affected sites. Here, we have developed a fibrin formulation that allows adipose-derived mesenchymal stromal cells (ADSCs) to form tubular structures in vitro. The tubular structures express markers of endothelium, including CD31 and VE-Cadherin, as well as the pericyte marker NG2. The ability for the MSCs to form tubular structures within the fibrin gels was directly dependent on the stoichiometric ratios of thrombin and fibrinogen and the resulting gel concentration, as well as on the presence of bFGF. Fibrin gel formulations that varied in stiffness were tested. ADSCs that are embedded in a stiff fibrin formulation express VE-cadherin and CD31 as shown by PCR, FACS and immunostaining. Confocal imaging analysis demonstrated that tubular structures formed, containing visible lumens, in the stiff fibrin gels in vitro. There was also a difference in the amounts of bFGF secreted by ADSCs grown in the stiffer gels as compared to softer gels. Additionally, hAT-MSCs gave rise to perfusable vessels that were VE-cadherin positive after subcutaneous injection into mice, whereas the softer fibrin formulation containing ADSCs did not. The application of ADSCs delivered in the stiff fibrin gels allowed for the wounds to heal more quickly, as assessed by wound size, amount of granulation tissue and collagen content. Interestingly, following 5 days of healing, the ADSCs remained within the fibrin gel and did not integrate into the granulation tissue of healing wounds in vivo. These data show that ADSCs are able to form tubular structures within fibrin gels, and may also contribute to faster wound healing, as compared with no treatment or to wounds treated with fibrin gels devoid of ADSCs.
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影响因子：
14
作者：
Park, Jennifer S.;Chu, Julia S.;Tsou, Anchi D.;Diop, Rokhaya;Tang, Zhenyu;Wang, Aijun;Li, Song
通讯作者：
Li, Song
影响因子：
8.8
作者：
Chen PY;Qin L;Barnes C;Charisse K;Yi T;Zhang X;Ali R;Medina PP;Yu J;Slack FJ;Anderson DG;Kotelianski V;Wang F;Tellides G;Simons M
通讯作者：
Simons M
影响因子：
4.1
作者：
Benavides, Omar M.;Petsche, Jennifer J.;Jacot, Jeffrey G.
通讯作者：
Jacot, Jeffrey G.
术语羊膜是多能间充质干细胞的高吞吐量来源，能够在体外分化为内皮细胞。
影响因子：
--
作者：
Alviano, Francesco;Fossati, Valentina;Marchionni, Cosetta;Arpinati, Mario;Bonsi, Laura;Franchina, Michele;Lanzoni, Giacomo;Cantoni, Silvia;Cavallini, Claudia;Bianchi, Francesca;Tazzari, Pier Luigi;Pasquinelli, Gianandrea;Foroni, Laura;Ventura, Carlo;Grossi, Alberto;Bagnara, Gian Paolo
通讯作者：
Bagnara, Gian Paolo
影响因子：
7.5
作者：
Sorrell JM;Caplan AI
通讯作者：
Caplan AI