Stem cell Trial of recovery EnhanceMent after Stroke 2 (STEMS 2) pilot randomised controlled trial

运动障碍是中风的常见结果，会导致相当大的身体残疾和痛苦。干细胞是新大脑和支持细胞的潜在来源，通过直接转变为不同的细胞类型，或者通过刺激局部脑干细胞改变。骨髓干细胞(所谓的CD34+细胞)可以通过粒细胞集落刺激因子(G-CSF)进入血液循环，粒细胞集落刺激因子是一种自然产生的激素，控制着某些骨髓细胞。我们之前已经在36名近期中风患者中完成了G-CSF的先导性随机试验；根据剂量的不同，G-CSF使血液CD34+细胞计数增加了10倍。G-CSF似乎是安全的，我们现在需要探索循环CD34+细胞的增加如何改善中风后的预后。我们在卒中发病7天后招募的60名患者中开始了第二个试点试验，以进一步评估G-CSF对安全性的影响。我们正在使用脑部磁共振成像来评估受损部位是否缩小，该区域的细胞内容是否恢复，细胞之间的连接是否重新发展，该区域的血液供应是否改善，以及CD34+细胞是否可以被追踪到受损的中风区域。如果患者死亡，将在显微镜下对大脑进行检查，以评估中风区域是否存在CD34+干细胞。如果这项研究支持G-CSF可能有助于中风后恢复的观点，结果将有助于设计未来G-CSF在最近中风中的试验设计。即使试验没有显示任何效果，这项研究的经验也将为未来干细胞试验如何进行提供有用的信息。如果后续试验呈阳性，常规使用G-CSF将使患者和社会受益，减轻护理人员和医疗保健的负担，并为英国政府的卫生战略做出贡献。

Disordered movement is a common result of stroke and causes considerable physical disability and distress. Stem cells are a potential source of new brain and supporting cells, either by directly changing into the different cell types, or by stimulating local brain stem cells to change. Bone marrow stem cells (so-called CD34+ cells) may be moved into the blood circulation using granulocyte-colony stimulating factor (G-CSF), a naturally occurring hormone which controls certain bone marrow cells. We have previously completed a pilot randomised trial of G-CSF in 36 patients with recent stroke; G-CSF increased blood CD34+ cell counts by up to ten times depending on dose. G-CSF appeared safe and we now need to explore how the increase in circulating CD34+ cells might improve outcome after stroke. We have started a second pilot trial in 60 patients recruited 7 days after stroke onset to further assess the effects of G-CSF on safety. We are using magnetic resonance imaging of the brain to assess whether the site of damage reduces in size, whether cell content recovers in this area, whether connections between cells re-develop, whether the blood supply in this area improves, and whether CD34+ cells can be tracked moving to the damaged stroke region. If patients die, examination of the brain under a microscope will be performed assessing whether CD34+ stem cells are present in area of the stroke. If this study supports the idea that G-CSF may aid recovery after stroke, the results will help in the design of future trials of G-CSF in recent stroke. Even if the trial shows no effect, lessons from the study will provide useful information on how future trials of stem cells might be performed. If subsequent trials are positive, routine use of G-CSF would benefit patients and society, reduce load on carers and health care, and contribute to the UK Government‘s health strategy.