Engineered Fibrin Gels for Parallel Stimulation of Mesenchymal Stem Cell Proangiogenic and Osteogenic Potential.
Engineered Fibrin Gels for Parallel Stimulation of Mesenchymal Stem Cell Proangiogenic and Osteogenic Potential.
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DOI：
10.1007/s10439-014-1227-x
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发表时间：
2015-08
影响因子：
3.8
通讯作者：
Leach, J. Kent
中科院分区：
文献类型：
--
作者：
Murphy, Kaitlin C.;Hughbanks, Marissa L.;Binder, Bernard Y. K.;Vissers, Caroline B.;Leach, J. Kent
间充质干/基质细胞（MSC）正在研究用于细胞疗法以修复由创伤或疾病引起的骨缺损。间充质干细胞分泌促血管生成因子，并可被诱导分化成骨形成成骨细胞，但有有限的证据表明，这些事件可以并行实现。细胞递送载体性质的操纵代表用于指导MSC在骨愈合中的功能的候选方法。我们假设纤维蛋白凝胶的生物物理特性可以同时调节包埋的MSC的促血管生成和成骨潜力。通过补充NaCl（1.2、2.3和3.9%w/v）以调节凝胶生物物理性质而不改变蛋白质浓度来形成纤维蛋白凝胶。包埋在1.2%w/v NaCl凝胶中的MSC在体外是最促血管生成的，而在3.9%w/v凝胶中的细胞表现出最大的成骨反应。与其他组相比，包埋在2.3%w/v凝胶中的MSC提供了促血管生成潜力、成骨潜力和凝胶收缩性之间的最佳平衡。然后检查当在2.3%w/v NaCl凝胶中展开并植入到辐照的原位骨缺损中时MSC对骨修复的贡献。与植入3周后的脱细胞凝胶相比，用MSC负载的纤维蛋白凝胶治疗的缺损显示出血管密度、早期成骨、上级形态学显著增加，以及修复组织的细胞结构增加。与空白凝胶相比，12周后用MSC负载的凝胶治疗的缺损表现出骨形成增加。这些结果证实，可以调节纤维蛋白凝胶的性质，以同时促进MSC的促血管生成和成骨潜力，并且通过补充NaCl修饰的纤维蛋白凝胶是MSC刺激体内骨修复的有前途的载体。
Mesenchymal stem/stromal cells (MSCs) are under examination for use in cell therapies to repair bone defects resulting from trauma or disease. MSCs secrete proangiogenic cues and can be induced to differentiate into bone-forming osteoblasts, yet there is limited evidence that these events can be achieved in parallel. Manipulation of the cell delivery vehicle properties represents a candidate approach for directing MSC function in bone healing. We hypothesized that the biophysical properties of a fibrin gel could simultaneously regulate the proangiogenic and osteogenic potential of entrapped MSCs. Fibrin gels were formed by supplementation with NaCl (1.2, 2.3, and 3.9% w/v) to modulate gel biophysical properties without altering protein concentrations. MSCs entrapped in 1.2% w/v NaCl gels were the most proangiogenic in vitro, yet cells in 3.9% w/v gels exhibited the greatest osteogenic response. Compared to the other groups, MSCs entrapped in 2.3% w/v gels provided the best balance between proangiogenic potential, osteogenic potential, and gel contractility. The contribution of MSCs to bone repair was then examined when deployed in 2.3% w/v NaCl gels and implanted into an irradiated orthotopic bone defect. Compared to acellular gels after 3 weeks of implantation, defects treated with MSC-loaded fibrin gels exhibited significant increases in vessel density, early osteogenesis, superior morphology, and increased cellularity of repair tissue. Defects treated with MSC-loaded gels exhibited increased bone formation after 12 weeks compared to blank gels. These results confirm that fibrin gel properties can be modulated to simultaneously promote both the proangiogenic and osteogenic potential of MSCs, and fibrin gels modified by supplementation with NaCl are promising carriers for MSCs to stimulate bone repair in vivo.
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影响因子：
9.7
作者：
Jose, Soumia;Hughbanks, Marissa L.;Binder, Bernard Y. K.;Ingavle, Ganesh C.;Leach, J. Kent
通讯作者：
Leach, J. Kent
影响因子：
45.3
作者：
Dorresteijn, LDA;Kappelle, AC;Bartelink, H
通讯作者：
Bartelink, H
影响因子：
3.3
作者：
Kagiwada, Harumi;Yashiki, Tetsuya;Ohgushi, Hajime
通讯作者：
Ohgushi, Hajime
影响因子：
4.1
作者：
He, Jiawei;Genetos, Damian C.;Leach, J. Kent
通讯作者：
Leach, J. Kent
影响因子：
9.8
作者：
Decaris, Martin L.;Lee, Chang I.;Yoder, Mervin C.;Tarantal, Alice F.;Leach, J. Kent
通讯作者：
Leach, J. Kent