Reengineering autologous bone grafts with the stem cell activator WNT3A
Reengineering autologous bone grafts with the stem cell activator WNT3A
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DOI：
10.1016/j.biomaterials.2014.12.014
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发表时间：
2015-04-01
期刊：
影响因子：
14
通讯作者：
Helms, Jill A.
中科院分区：
文献类型：
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作者：
Jing, Wei;Smith, Andrew A.;Helms, Jill A.
自体骨移植是治疗骨缺损的标准治疗方法，但这种生物材料在老年患者中不可靠。自体移植物的功效可以追溯到存在于骨移植物内的多能干细胞。衰老减弱了这些干细胞的活力和功能，导致骨愈合率不一致。我们发现，年龄相关的变化，自体移植物的功效是由内源性Wnt信号的损失。使用Dkk 1阻断这种内源性Wnt信号消除了自体移植物功效，而以脂质体重构的WNT 3A蛋白（L-WNT 3A）的形式提供Wnt信号恢复了来自老年动物的自体移植物的骨形成潜力。生物工程自体移植物在宿主部位表现出明显更好的存活率。自体移植物中的间充质干细胞和骨骼干细胞群被L-WNT 3A激活，并且有丝分裂活性和成骨分化显著增强。在脊柱融合模型中，与标准护理相比，用L-WNT 3A处理的老化自体移植物显示出上级骨形成能力。因此，在L-WNT 3A中的短暂孵育可靠地提高了自体骨移植的功效，这有可能显著改善老年患者的护理。(C)2014爱思唯尔有限公司版权所有。
Autologous bone grafting represents the standard of care for treating bone defects but this biomaterial is unreliable in older patients. The efficacy of an autograft can be traced back to multipotent stem cells residing within the bone graft. Aging attenuates the viability and function of these stem cells, leading to inconsistent rates of bony union. We show that age-related changes in autograft efficacy are caused by a loss in endogenous Wnt signaling. Blocking this endogenous Wnt signal using Dkk1 abrogates autograft efficacy whereas providing a Wnt signal in the form of liposome-reconstituted WNT3A protein (L-WNT3A) restores bone forming potential to autografts from aged animals. The bioengineered autograft exhibits significantly better survival in the hosting site. Mesenchymal and skeletal stem cell populations in the autograft are activated by L-WNT3A and mitotic activity and osteogenic differentiation are significantly enhanced. In a spinal fusion model, aged autografts treated with L-WNT3A demonstrate superior bone forming capacity compared to the standard of care. Thus, a brief incubation in L-WNT3A reliably improves autologous bone grafting efficacy, which has the potential to significantly improve patient care in the elderly. (C) 2014 Elsevier Ltd. All rights reserved.