Translation of remote control regenerative technologies for bone repair.
Translation of remote control regenerative technologies for bone repair.
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DOI：
10.1038/s41536-018-0048-1
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发表时间：
2018
影响因子：
7.2
通讯作者：
El Haj AJ
中科院分区：
文献类型：
--
作者：
Markides H;McLaren JS;Telling ND;Alom N;Al-Mutheffer EA;Oreffo ROC;Zannettino A;Scammell BE;White LJ;El Haj AJ
生物力学刺激，或力学转导，在正常骨稳态和修复中的作用被理解为促进体外间充质干细胞（MSC）的有效成骨。力学转导已被整合到众多的体外骨组织工程策略，并提供了一种有效的手段，控制细胞行为的治疗结果。然而，植入后向外源性MSC群体递送机械刺激造成了显著的转化障碍。在这里，我们描述了一种创新的生物磁性策略，云母，其中磁性纳米颗粒（MNP）用于远程传递机械刺激的机械受体，TREK-1，导致激活和下游信号通过外部磁性阵列。在这些研究中，我们将云母转化为临床前骨损伤绵羊模型，以评估功能性骨修复。我们描述了一种磁阵列的发展，能够在体内MNP操作和随后的成骨在体外同等的场强。我们进一步证明了MICA激活的MSC在体内的生存能力在植入后48小时不受影响。我们目前的证据支持早期加速修复和初步增强骨生长的MICA激活的缺陷相比，内部控制的个人。在体外评估供体对MICA活化的反应的可变性，揭示成骨潜力差的供体通过MICA活化得到最大改善。我们的研究结果表明，在体外和体内反应云母之间的明确关系。这些独特的实验为基于细胞的疗法提供了令人兴奋的临床应用，作为在没有药理学试剂的情况下实时动态加载的实际体内来源。一种刺激成体干细胞的生物磁疗法有助于促进绵羊骨损伤模型的修复。来自英国基尔大学的Alicia El Haj及其同事先前开发了一种通过使用靶向磁性纳米颗粒和小磁场激活干细胞上特定离子通道受体的技术，但他们没有在任何大于小鼠的物体上尝试过这种方法。在这里，科学家们在腿骨受伤的羊身上测试了这项技术。他们设计了一种与羊腿兼容的磁性阵列，可以刺激细胞进行修复。然后，他们用纳米颗粒标记骨髓干细胞，将标记的细胞植入受伤部位，并在腿部周围应用外部磁性阵列。与非磁增强干细胞治疗相比，该疗法加速了修复并增强了骨骼生长。
The role of biomechanical stimuli, or mechanotransduction, in normal bone homeostasis and repair is understood to facilitate effective osteogenesis of mesenchymal stem cells (MSCs) in vitro. Mechanotransduction has been integrated into a multitude of in vitro bone tissue engineering strategies and provides an effective means of controlling cell behaviour towards therapeutic outcomes. However, the delivery of mechanical stimuli to exogenous MSC populations, post implantation, poses a significant translational hurdle. Here, we describe an innovative bio-magnetic strategy, MICA, where magnetic nanoparticles (MNPs) are used to remotely deliver mechanical stimuli to the mechano-receptor, TREK-1, resulting in activation and downstream signalling via an external magnetic array. In these studies, we have translated MICA to a pre-clinical ovine model of bone injury to evaluate functional bone repair. We describe the development of a magnetic array capable of in vivo MNP manipulation and subsequent osteogenesis at equivalent field strengths in vitro. We further demonstrate that the viability of MICA-activated MSCs in vivo is unaffected 48 h post implantation. We present evidence to support early accelerated repair and preliminary enhanced bone growth in MICA-activated defects within individuals compared to internal controls. The variability in donor responses to MICA-activation was evaluated in vitro revealing that donors with poor osteogenic potential were most improved by MICA-activation. Our results demonstrate a clear relationship between responders to MICA in vitro and in vivo. These unique experiments offer exciting clinical applications for cell-based therapies as a practical in vivo source of dynamic loading, in real-time, in the absence of pharmacological agents. A biomagnetic therapy that stimulates adult stem cells helps promote repair in a sheep model of bone injury. Alicia El Haj from Keele University, UK, and colleagues previously developed a technique for activating specific ion channel receptors on stem cells through the use of targeted magnetic nanoparticles and a small magnetic field, but they had not tried the method on anything larger than a mouse. Here, the scientists tested the technique on sheep with injuries to their leg bones. They designed a magnetic array compatible with a sheep leg which could stimulate the cells for repair. They then tagged bone marrow stem cells with the nanoparticles, implanted the tagged cells at the site of injury, and applied an external magnetic array around the leg. The therapy accelerated repair and enhanced bone growth
compared to non-magnetically enhanced stem-cell treatments.
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影响因子：
--
作者：
Kretlow JD;Jin YQ;Liu W;Zhang WJ;Hong TH;Zhou G;Baggett LS;Mikos AG;Cao Y
通讯作者：
Cao Y
影响因子：
4
作者：
Gronthos, Stan;McCarty, Rosa;Zannettino, Andrew C. W.
通讯作者：
Zannettino, Andrew C. W.
影响因子：
--
作者：
Lee S;Choi E;Cha MJ;Hwang KC
通讯作者：
Hwang KC
影响因子：
4.1
作者：
Charoenpanich, Adisri;Wall, Michelle E.;Loboa, Elizabeth G.
通讯作者：
Loboa, Elizabeth G.
影响因子：
4.9
作者：
Knight, M. Noelle;Hankenson, Kurt D.
通讯作者：
Hankenson, Kurt D.