Mesenchymal stroma cells trigger early attraction of M1 macrophages and endothelial cells into fibrin hydrogels, stimulating long bone healing without long-term engraftment
Mesenchymal stroma cells trigger early attraction of M1 macrophages and endothelial cells into fibrin hydrogels, stimulating long bone healing without long-term engraftment
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DOI：
10.1016/j.actbio.2014.07.017
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发表时间：
2014-11-01
影响因子：
9.7
通讯作者：
Richter, Wiltrud
中科院分区：
文献类型：
--
作者：
Seebach, Elisabeth;Freischmidt, Holger;Richter, Wiltrud
间充质基质细胞（MSCs）的植入是一种有吸引力的方法，以刺激关闭大骨缺损，但最佳的载体尚未确定。MSC可以显示营养和/或免疫调节功能或通过其成骨活性刺激骨愈合。本研究的目的是阐明纤维蛋白水凝胶是否支持植入的MSC在长骨缺损中的早期作用，例如宿主细胞募集、免疫调节和组织再生。雌性大鼠接受无细胞纤维蛋白或雄性MSC包埋在纤维蛋白载体板稳定的股骨骨缺损。分析移除的愈伤组织的宿主细胞侵袭（第6天）、局部细胞因子表达（第3天和第6天）和雄性MSC的持久性（第3、6、14和28天）。纤维蛋白-MSC复合物引发宿主细胞快速吸引到水凝胶中，而无细胞纤维蛋白植入物不被侵入。M1巨噬细胞和内皮祖细胞占主导地位的迁移前沿形成，而M2巨噬细胞仍然稀疏。只有MSC接种的纤维蛋白水凝胶刺激早期组织成熟和原始血管形成在第6天与显着较高的VEGF mRNA水平记录在第3天。局部TNF-α、IL-1 β和IL-10表达表明平衡的免疫细胞活性，与MSC植入无关。植入的MSC持续到第14天，但不是第28天。我们的研究结果表明，纤维蛋白水凝胶是一个有吸引力的载体MSC植入到长骨缺损，支持宿主细胞的吸引力和促血管生成活性。通过这种血管生成，植入物整合和组织成熟在长骨愈合中受到刺激，而不依赖于植入的MSC的长期植入。(C)2014 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Implantation of mesenchymal stroma cells (MSCs) is an attractive approach to stimulate closure of large bone defects but an optimal carrier has yet to be defined. MSCs may display trophic and/or immunomodulatory features or stimulate bone healing by their osteogenic activity. The aim of this study was to unravel whether fibrin hydrogel supports early actions of implanted MSCs, such as host cell recruitment, immunomodulation and tissue regeneration, in long bone defects. Female rats received cell-free fibrin or male MSCs embedded in a fibrin carrier into plate-stabilized femoral bone defects. Removed callus was analyzed for host cell invasion (day 6), local cytokine expression (days 3 and 6) and persistence of male MSCs (days 3, 6, 14 and 28). Fibrin-MSC composites triggered fast attraction of host cells into the hydrogel while cell-free fibrin implants were not invaded. A migration front dominated by M1 macrophages and endothelial progenitor cells formed while M2 macrophages remained sparse. Only MSC-seeded fibrin hydrogel stimulated early tissue maturation and primitive vessel formation at day 6 in line with significantly higher VEGF mRNA levels recorded at day 3. Local TNF-alpha, IL-1 beta and IL-10 expression indicated a balanced immune cell activity independent of MSC implantation. Implanted MSCs persisted until day 14 but not day 28. Our results demonstrate that fibrin hydrogel is an attractive carrier for MSC implantation into long bone defects, supporting host cell attraction and pro-angiogenic activity. By this angiogenesis, implant integration and tissue maturation was stimulated in long bone healing independent of long-term engraftment of implanted MSCs. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.