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Sci Transl Med:以色列学者揭示猪体内微泡可帮助断骨愈合

摘要 : 2017年5月17日,国际顶尖学术期刊《Science》旗下《Science Translational Medicine》杂志上在线发表了以色列耶路撒冷希伯莱大学Maxim Bez研究员的一篇研究论文,论文报道了研究人员研发出了一个亟需的骨移植替代疗法,它可帮助减少与非愈合性骨折相关的长期住院、伤残及医疗系统的大量支出。

2017年5月17日,国际顶尖学术期刊《Science》旗下《Science Translational Medicine》杂志上在线发表了以色列耶路撒冷希伯莱大学Maxim Bez研究员的一篇研究论文,论文报道了研究人员研发出了一个亟需的骨移植替代疗法,它可帮助减少与非愈合性骨折相关的长期住院、伤残及医疗系统的大量支出。美国每年大约有10万个骨折愈合不良病例,它们导致了不愈合性骨折;全世界每年需要做的骨移植术超过2百万例,目的都是为了治疗这些难治性创伤。但是,从病人身上取新鲜骨常常很痛,而器官组织库中捐赠的移植用骨常常无法与接受者的器官组织融为一体。

如今,Maxim Bez和同事设计了一个分成两步的基因疗法,该疗法与FDA批准的超声波和微泡相结合,令猪体内的非愈合骨折在治疗8个星期内完全愈合。首先,研究人员在骨折断裂处放置了胶原蛋白支架,旨在给骨祖细胞提供一个友善的利基。接着,他们给猪注射含有混合骨生长因子基因材料的微泡。由超声棒发出的声波脉冲可促进祖细胞对生长因子DNA的摄取,后者可刺激骨生长。与其它依赖病毒载体递送治疗物质的基因疗法不同(这类方法颇有风险,因为病毒会永久性地整合到基因组内,并在以后促使癌变或引发致命性免疫反应),用超声波和微泡的基因疗法不会触发明显炎症,而在10天后也无法检测到引入基因的表达。这种方法被证明侵入性最小、安全而且能促进全骨愈合,而愈合的骨强度堪比黄金标准的骨移植手术。Bez等人说,经过进一步研发,他们的系统有可能有许多不同的组织工程应用。

原文链接:

In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs

原文摘要:

More than 2 million bone-grafting procedures are performed each year using autografts or allografts. However, both options carry disadvantages, and there remains a clear medical need for the development of new therapies for massive bone loss and fracture nonunios. We hypothesized that localized ultrasound-mediated, microbubble-enhanced therapeutic gene delivery to endogenous stem cells would induce efficient bone regeneration and fracture repair. To test this hypothesis, we surgically created a critical-sized bone fracture in the tibiae of Yucatán mini-pigs, a clinically relevant large animal model. A collagen scaffold was implanted in the fracture to facilitate recruitment of endogenous mesenchymal stem/progenitor cells (MSCs) into the fracture site. Two weeks later, transcutaneous ultrasound-mediated reporter gene delivery successfully transfected 40% of cells at the fracture site, and flow cytometry showed that 80% of the transfected cells expressed MSC markers. Human bone morphogenetic protein-6 (BMP-6) plasmid DNA was delivered using ultrasound in the same animal model, leading to transient expression and secretion of BMP-6 localized to the fracture area. Micro–computed tomography and biomechanical analyses showed that ultrasound-mediated BMP-6 gene delivery led to complete radiographic and functional fracture healing in all animals 6 weeks after treatment, wheras nonunio was evident in control animals. Collectively, these findings demonstrate that ultrasound-mediated gene delivery to endogenous mesenchymal progenitor cells can effectively treat nonhealing bone fractures in large animals, thereby addressing a major orthopedic unmet need and offering new possibilities for clinical translation.

来源: Science Translational Medicine 浏览次数:0

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