中国组织工程研究

中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (13): 1998-2002.doi: 10.3969/j.issn.2095-4344.2017.13.006

• 造血干细胞 hematopoietic stem cells • 上一篇    下一篇

外周血CD34+细胞自体移植促进老年动脉粥样性缺血肢体的血管新生：前瞻性、单中心、开放性、随机对照临床试验方案

周晨虹1，徐丽丽2，郝秀仙3，孙晓娟1，郭明金2，刘  兵2   

  1. 1青岛市第九人民医院，山东省青岛市  266000；2青岛大学附属医院，山东省青岛市  266000；3青岛市中心医院，山东省青岛市  266000
  • 修回日期:2017-03-18 出版日期:2017-05-08 发布日期:2017-06-09
  • 通讯作者: 刘兵，青岛大学附属医院，山东省青岛市 266000
  • 作者简介:周晨虹，副主任医师。 并列第一作者：徐丽丽。
  • 基金资助:

    2016年山东省医药卫生科技发展计划课题[(2016)年第 HW027号]

Autologous CD34+ cell transplantation promotes angiogenesis in older adult patients with atherosclerotic ischemia: study protocol for a prospective, single-center, open-label, randomized controlled clinical trial

Zhou Chen-hong1, Xu Li-li2, Hao Xiu-xian3, Sun Xiao-juan1, Guo Ming-jin2, Liu Bing2   

  1. 1Qingdao No. 9 People’s Hospital, Qingdao 266000, Shandong Province, China; 2the Affiliated Hospital of Qingdao University, Qingdao 266000; Shandong Province, China; 3Qingdao Central Medical Center, Qingdao 266000, Shandong Province, China
  • Revised:2017-03-18 Online:2017-05-08 Published:2017-06-09
  • Contact: Liu Bing, the Affiliated Hospital of Qingdao University, Qingdao 266000; Shandong Province, China
  • About author:Zhou Chen-hong, Associate chief physician, Qingdao No. 9 People’s Hospital, Qingdao 266000, Shandong Province, China Xu Li-lI, the Affiliated Hospital of Qingdao University, Qingdao 266000; Shandong Province, China Zhou Chen-hong and Xu Li-li contributed equally to this work.
  • Supported by:

    the Medical and Health Scientific Development Project of Shandong Province in 2016, No. (2016)HW027

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摘要：

文章快速阅读：

 

文题释义：
动脉硬化闭塞症：动脉硬化闭塞症是一种全身性、退行性病变，是大、中动脉的基本病理过程，主要是细胞纤维基质、脂质和组织碎片的异常沉积，在动脉内膜或中层发生增生过程中复杂的病理变化在周围血管疾患中，动脉的狭窄、闭塞性或动脉瘤性病变几乎大部分都是由动脉硬化所引起。
糖尿病足：是指糖尿病患者足部由于神经病变使下肢保护功能减退，大血管和微血管病变使动脉灌注不足致微循环障碍而发生溃疡和坏疽的疾病状态。

 

摘要
背景：老年动脉硬化闭塞症的主要临床表现为下肢缺血，目前治疗较为困难。自体干细胞移植可将干细胞移植到缺血的肢体肌肉中，使其分化形成新生毛细血管，改善和恢复下肢血流，达到治疗下肢缺血的目的。目前已有研究证实，内皮祖细胞标记物CD34+细胞移植可促进动物的缺血肢体的血管新生。
目的：试验假设采用老年动脉粥样性缺血患者外周血的CD34+细胞自体移植，可有效促进血管新生。
方法：研究为前瞻性、单中心、开放性、随机对照临床试验，在中国山东省，青岛大学附属医院完成。纳入老年动脉粥样性下肢缺血患者20例，随机分为2组，细胞移植组10例采用促血管生长因子-血管内皮生长因子165基因转染并纯化老年下肢动脉粥样硬化性缺血患者外周血的CD34+细胞，自体移植至缺血侧肢体肌肉组织；对照组10例于缺血肌肉组织内注射生理盐水，随访6个月。试验的主要观察指标为两组移植前和移植后6个月踝肱指数的变化以评估下肢缺血情况。试验的次要观察指标为移植前和移植后6个月下肢肌肉组织微血管数量变化，CT血管成像显示的新生血管形态；移植后6个月患者血管内皮生长因子免疫阳性细胞数及不良反应发生率。试验在北美临床试验注册中心注册(NCT03098771)。试验经中国山东省青岛大学附属医院伦理委员会批准。研究符合世界医学会制定的《赫尔辛基宣言》的要求。参与者本人对治疗方案和过程均知情同意，并签署知情同意书。
讨论：试验拟2018年1月开始，2019年12月完成，希望证实血管内皮生长因子165基因转染修饰的CD34+细胞移植治疗老年动脉粥样性缺血肢体的确切疗效，研究结果有助于开拓下肢缺血性疾病治疗的新模式。

 

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程
ORCID: 0000-0001-6104-753X(周晨虹)

关键词: 干细胞, 移植, 干细胞移植, 自体移植, CD34+细胞, 老年, 动脉粥样性缺血肢体, 血管新生, 血管内皮生长因子, 临床试验

Abstract:

BACKGROUND: The main clinical manifestation of senile arteriosclerosis obliterans is lower limb ischemia, which is currently difficult to treat. One method is by autologous stem cell transplantation into the muscles of ischemic limbs to improve the formation of new capillaries and restore lower limb blood flow. Endothelial progenitor cell marker CD34+ cell transplantation has been shown to promote angiogenesis in ischemic limbs. Therefore, we propose that peripheral blood autologous CD34+ cell transplantation in older adult patients with atherosclerotic ischemia could effectively promote angiogenesis.
OBJECTIVE: To assume that peripheral blood autologous CD34+ cell transplantation in the elderly with atherosclerotic ischemia could effectively promote angiogenesis.
METHODS: This is a prospective, single-center, open-label, randomized, and controlled clinical trial that will be completed at the Qingdao No. 9 People’s Hospital, China. Twenty older adult patients with atherosclerotic lower limb ischemia will be randomized into two groups. In the cell transplantation group (n=10), peripheral blood CD34+ cells transfected with vascular endothelial growth factor 165 (VEGF165) gene will be intramuscularly transplanted into the ischemic limbs in older adult patients with atherosclerotic lower limb ischemia. In the control group (n=10), normal saline will be intramuscularly injected into the ischemic limbs. All patients will be followed up for 6 months. The primary outcome will be ankle-brachial indices before and 6 months after transplantation to assess lower limb ischemia in both groups. The secondary outcomes will be the number of microvessels in the lower limb muscles before and 6 months after transplantation, the morphology of new blood vessels revealed by CT angiography, the number of VEGF-immunoreactive cells 6 months after transplantation and the incidence of adverse reactions. The trial was registered at the ClinicalTrials.gov (identifier: NCT03098771), and the study protocol was approved by the Ethics Committee of Qingdao No. 9 People’s Hospital of China. All protocols will be in accordance with Declaration of Helsinki, formulated by the World Medical Association. All patients will be informed of study protocols and provide a written informed consent prior to the beginning of the trial.
DISCUSSION: This trial will begin in January 2018 and finish in December 2019. We aim to quantify the effects of VEGF165 gene-modified CD34+ cell transplantation in the treatment of older adult patients with atherosclerotic ischemia to develop a new effective treatment of lower limb ischemia.

 

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Stem Cells, Vascular Endothelial Growth Factors, Tissue Engineering

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