自体骨髓单个核细胞可安全治疗前壁心肌梗死后心力衰竭Autologous bone marrow mononuclear stem cells can be used safely to treat patients with heart failure after anterior myocardial infarction
聂颖,高炜,郭艳红,崔鸣,张永珍,郭丽君,郭静萱
摘要(Abstract):
目的评价经冠状动脉内注射自体骨髓单个核细胞治疗前壁心肌梗死后心力衰竭的安全性。方法15例前壁心肌梗死患者接受经皮冠状动脉介入治疗(PCI)和药物治疗同时,进行冠状动脉内自体骨髓单个核细胞移植。细胞治疗前后测定血浆及骨髓中CD34+细胞含量;移植前、移植后24h和随访12个月时分别测定血浆红细胞(RBC)、血红蛋白(Hb)、网织红细胞、D-二聚体(D-Dimer)、N末端B型钠尿肽原(NT-proBNP)、超敏C反应蛋白(highsensitive-C reactive protein,hs-CRP)、肌钙蛋白T(troponinT,TnT)、心肌型肌酸激酶同工酶(CK-MB)、尿素氮(blood urea nitrogen,BUN)、肌酐(creatinine,Cr)及尿酸(uricacid,UA)水平。入组及随访12个月时行动态心电图(Holter)评价心律失常发生情况,观察并记录移植前后及随访过程中发生的不良反应。结果分离后骨髓单个核细胞数量为(1.48±0.52)×109;CD34+细胞占1.28%±0.17%,数量为(18.57±9.14)×106。移植前循环血中CD34+细胞0.33%±0.12%,术后24h达峰值1.30%±0.35%,72h基本恢复至移植前水平0.53%±0.21%。移植后24h血浆NT-proBNP较移植前无显著性变化(1864.00±412.60μg/L比1864.00±369.70μg/L,P>0.05),随访12个月时较基线显著降低(701.05±154.60μg/L比1864.00±369.70μg/L,P<0.05)。移植后2、6、14、24h血浆TnT、CK-MB水平较移植前均无显著变化。与基线相比,移植后24h、12个月血浆RBC、Hb、网织红细胞、D-Dimer、hs-CRP及肝、肾功能均无显著变化。术后12个月随访未见恶性心律失常发生。结论经冠状动脉注射骨髓单个核细胞未引起微栓塞、炎症反应及心肌损伤,不诱发或加重心力衰竭,对血液系统、肝、肾功能及凝血功能无影响,长期随访未见与移植相关的严重不良反应。本研究提示经冠状动脉注射自体骨髓单个核细胞治疗方法是安全、可行的。
关键词(KeyWords): 心肌梗死;造血干细胞移植;心力衰竭,充血性
基金项目(Foundation): 国家重点基础研究发展计划(973计划)(编号:2007cb512107)
作者(Author): 聂颖,高炜,郭艳红,崔鸣,张永珍,郭丽君,郭静萱
参考文献(References):
- [1]Janssens S,Dubios C,Bogaert J,et al.Autologous bone mar.row.derived stem cell transfer in patients with ST.segment eleva.tion myocardial infarction:double.blind randomized controlled trial.Lancet,2006,367:113.121.
- [2]Meyer GP,Wollert KC,Lotz J,et al.Intracoronary bone marrow cell transfer after myocardial infarction.Eighteen Month′s follow.up data from the randomized,controlled BOOST(Bone marrow transfer enhance ST.elevation infarct regeneration)Trial.Circu.lation,2006,113:1287.1294.
- [3]Korbling M,Estrov Z.Adult stem cells for tissue repair.a new therapeutic concept?N Engl J Med,2003,349:570.582.
- [4]Kocher AA,Schuster MD,Szabolcs MJ,et al.Neovasculariza.tion of ischemic myocardium by human bone.marrow.derived an.gioblasts prevents cardiomyocyte apoptosis,reduces remodeling and improves cardiac function.Nat Med,2001,7:430.436.
- [5]Kang HJ,Kim HS,Zhang SH.Y,et al.Effects of intracoronary infusion of peripheral blood stem.cells mobilized with granulo.cyte.colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction:the MAGIC cell randomized clinical trial.Lancet,2004,363:751.756.
- [6]Skowasch D,Jabs A,Andrie R,et al.Presence of bone.marrow and neural.crest.derived cells in intimal hyperplasia at the time of clinical in.stent restenosis.Cardiovasc Res,2003,60:684.691.
- [7]Lunde K,Sdheim S,Ackhus S,et al.Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction.N Engl J Med,2006,355:1199.1201.
- [8]Yoon YS,Park JS,Tkebuchava U,et al.Unexpected severe cal.cification after transplantation of bone marrowcells in acute myo.cardial infarction.Circulation,2004,109:3154.3157.
- [9]Orlic D,Kajstura J,Chimenti S,et al.Bone marrowcells regen.erate infarcted myocardium.Nature,2001,410:701.705.
- [10]Strauer BE,Brehm M,Zeus T,et al.Repair of infarcted myo.cardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans.Circulation,2002,106:1913.1918.
- [11]Dimmeler S,Zeiher AM,Schneider MD.Unchain my heart:the scientific foundations of cardiac repair.Clin Invest,2005,115:572.583.
- [12]Schachinger V,Assmus B,Britten MB,et al.Transplantation of progenitor cells and regeneration enhancement in acute myocardi.al infarction.Final One.Year Results of the TOPCARE.AMI Tri.al.J Am Coll Cardiol,2004,44:1690.1699.
- [13]Ince H,Petzsch M,Kleine HD,et al.Preservation from left ventricular remodeling by front.integrated revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulocyte.colony.stimulating factor(FIRSTLINE.AMI).Circulation,2005,112:3097.3106.
- [14]Jaffe AS,Babuin L,Apple FS.Biomarkers in acute cardiac dis.ease,the present and the future.J Am Coll Cardiol,2006,48:1.11.
- [15]谢良麟,王宪.C反应蛋白与动脉粥样硬化.生理科学进展,2004,35:113.118.