血小板衍生的生长因子影响创伤后干细胞增殖

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A study published today inBMC Medicinereports on thefirstinvestigation表明血小板衍生的生长因子与骨折修复有关,通过募集间充质干细胞In this guest post, co-authors,,,,Peter Giannoudis, Hiang Boon Tan and Elena Jones研究解释了研究

对使用干细胞重建组织和受创伤或疾病损害的器官的兴趣增加了。干细胞是形成这些组织的成熟细胞的前身,可以在定义的化学和生物力学因子下驱动以形成成熟的细胞和细胞外基质,从而形成模仿天然的替代组织。

In the last 10-20 years, major scientific and industrial effort has been directed towards developing technologies for expanding stem cells outside the human body but these technologies remain expensive and difficult to use clinically, not least because stem cells need animal-derived reagents to grow and these reagents can cause animal pathogen transmission to humans.

On the other hand, the behaviour of stem cells inside the human body, and their responses to injury or disease, remain poorly understood. For example, it is still unclear whether stem cells increase in their number after trauma and whether they can migrate, via bloodstream, to the damaged tissues and subsequently, rebuild them. Additionally, migrated stem cells can interact with tissue-resident cells and induce them to perform the necessary repairs. Although this has been proven to be true in some mouse model studies, small animal physiology differs significantly to that of humans.

Mesenchymal stem cells in trauma patients

In our study we investigated whether the severity of skeletal trauma is the factor influencing stem cell behavior in humans. We addressed this question by recruiting patients from two trauma groups (isolated trauma/damage to a single bone and polytrauma/damage to multiple bones) and also analyzed their bone marrow resident mesenchymal stem cells (MSCs) immediately after injury and a few days later.

两组中,我们没有观察到MSC释放到外周血中,这表明从骨髓到受损区域的直接干细胞转运是不可能的。但是,我们观察到创伤后MSC的特征确实发生了变化。它们与循环血小板数量的直接关系增加了,并且还增加了受体的丰度到其表面上的血小板衍生生长因子。换句话说,MSC已“动员”,并获得了必要的弹药来对抗损害发生后不久。

这些事件发生在一个不同的年代ite to injury, our data indicate that similar stem cell ‘mobilization’ could very likely take place at the site of damage and that the whole process may be controlled centrally via platelet derived growth factors and other yet unknown factors released into the blood. If these unknown factors are fully uncovered, it opens up a new opportunity to manipulate patient’s stem cells without taking them outside the body.

Research by the Leeds MSC group

The Academic Unit of Trauma and Orthopaedics at Leeds General Infirmary, headed byProfessor Peter Giannoudis长期以来一直是骨再生钻石概念的拥护者。它促进了许多因素的需求,以允许发生最佳的骨修复过程。这四个因素包括存在再生细胞(MSC),推动其反应的适当生长因子,有机基质或支架对“房屋” MSC,非常重要的是,稳定的机械环境。关于这个概念,当前的研究不仅突出了MSC后创伤后的生理行为,还表明可以从患者自己的血液中取出必要的生长因子。当前批准其在临床中使用的生长因子,例如骨形态发生蛋白,是由重组DNA技术(来自中国仓鼠卵巢细胞)产生的,价格昂贵,并且不存在不良的副作用。我们的研究表明,可以开发新技术以批量产生这些增长因素,例如与国家输血服务合作。

The Leeds MSC group started in 2001 as collaboration betweenDr Elena Jones((a stem cell biologist) and教授丹尼斯·麦格纳格尔(Dennis McGonagle)(风湿病学家)旨在在人骨髓中找到MSC的真实身份。2002年,他们发表了一项研究描述如何从人体骨髓中找到和分离MSC无需扩大文化。接下来是许多文章,研究了关节组织中MSC的性质和不同类型的骨骼。Hiang Boon Tan博士是一位有抱负的骨科学术培训生,他从事这项工作,以此作为他的研究生学习的一部分所描述的研究。

To summarize, following traumatic injury MSCs increase in numbers in direct relationship to circulating numbers of blood platelets. MSCs also increased the abundance of their surface receptors to platelet-derived growth factors. These alternations may be controlled centrally via factors released into the blood. Identification of these factors could open up a new opportunity to manipulate patient’s stem cells without taking them outside the body.

This work was made possible due to a unique collaboration between the Academic Unit of Trauma and Orthopaedics in Leeds General Infirmary and the Mesenchymal Stem Cell group located in Wellcome Trust Brenner Building, St James Hospital, Leeds. Both are part of Leeds Institute of Rheumatic and Musculoskeletal Medicine and have been supported by利兹肌肉骨骼生物医学研究单元(LMBRU)。LMBRU是NIHR资助的生物医学研究部门,旨在将利兹教学医院NHS Trust和Leeds大学之间的强大合作和高质量的肌肉骨骼研究活动汇集在一起​​。创伤部门是一个繁忙的重大创伤中心和英国三级复杂创伤案件管理中心;这是为了确保高质量的患者入院和招募这项研究的基础。

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Marie Benz, MD

洛杉矶生物医学研究所的医学博士Dennis Kim博士刚刚在《神经科学杂志》上发表了一项研究,显示接受血小板输血和DDAVP的患者以及头部创伤后未接受这种疗法的患者没有差异。

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