Chinese Journal of Tissue Engineering Research ›› 2018, Vol. 22 ›› Issue (9): 1463-1469.doi: 10.3969/j.issn.2095-4344.0480
Previous Articles Next Articles
Lu Meng-xiao1, Zheng Yuan-yuan1, Liu Yang2, Lu Jian-wei3, Li Peng3, Wu Ming-yuan3
Revised:
2017-11-27
Online:
2018-03-28
Published:
2018-04-03
Contact:
Liu Yang, Master, Senior Engineer, Eastern Union Stem Cell & Gene Engineering Co., Ltd., Huzhou 313000, Zhejiang Province, China
About author:
Lu Meng-xiao, Master, Zhejiang Cord Blood Bank (Huzhou), Huzhou 313000, Zhejiang Province, China
Supported by:
the Science and Technology Tackle Key Plan of Huzhou, No. 2016GG11
CLC Number:
Lu Meng-xiao, Zheng Yuan-yuan, Liu Yang, Lu Jian-wei, Li Peng, Wu Ming-yuan. Clinical treatment of heart failure by adult stem cells: existing problems and prospects[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(9): 1463-1469.
2.1 骨骼肌成肌细胞 骨骼肌成肌细胞来源于卫星细胞,是一类存在于肌纤维膜基底的骨骼肌前体细胞群。当肌肉损伤时,这些卫星细胞将会增殖和通过分化成肌小管和新的肌纤维促进肌肉再生[14]。这类细胞很容易从肌肉活检组织中获取,能在体外快速的扩增,且对低含氧和缺血情况具有抵抗力[15],因而骨骼肌成肌细胞率先被用到心力衰竭的临床前和临床研究中[16]。骨骼肌成肌细胞促进修复的能力已经在小动物心力衰竭模型与大动物心力衰竭模型中进行了验证。从动物实验中获得的鼓舞人心的结果很快转入到心力衰竭的临床试验中。 Menasche等[17-18]开展了一项Ⅰ期临床试验用于研究骨骼肌成肌细胞移植对于缺血性心肌病患者的安全性及可行性。10例患者左心室瘢痕区域注射8.71×108个自体成肌细胞,患者的NYHA级别从术前2.7±0.2降低到了术后1.6±0.1,同时射血分数从(24±1)%提高到了(32±1)%。63%的细胞植入左心室瘢痕区域显示使收缩压得到改善,试验中出现的2例死亡患者与细胞移植不相关,惟一与试验过程相关的严重不良事件可能是其中的4例患者发生了心律失常。此次结果表明自体骨骼肌成肌细胞移植治疗严重缺血性心肌病是安全且有效的。 Herreros等[19]同样开展了一项临床试验用于评估自体骨骼肌成肌细胞移植对心肌梗死患者的安全性及有效性。12例陈旧性心肌梗死和缺血性心肌病患者接受冠状动脉搭桥手术以及心肌内注射自体成肌细胞,患者的左心室射血分数在3周内由术前(35.5±2.3)%提高到了(53.50±4.98)%,同时使用骨骼肌成肌细胞治疗后心脏收缩性显著改善(基线水平室壁运动评分2.64±0.13 vs. 3个月时1.64±0.16),组织学证据显示成肌细胞在心肌中得到存活。结果同样证明了自体骨骼肌成肌细胞治疗心肌梗死是安全有效的。 根据这些有前景的试验结果,Menasche等[20]在左心室功能下降(射血分数≤ 35%)、心肌梗死及冠状动脉手术适应证患者中开展的一项多通道、随机、安慰剂对照、双盲Ⅱ期临床试验研究。患者接受骨骼肌成肌细胞或安慰剂治疗后安慰剂组、低剂量组、高剂量组在6个月和基线间的射血分数绝对变化分别为4.4%,3.4%,5.2%。与安慰剂组相比,成肌细胞高剂量组左心室体积明显减小,尽管在接受成肌细胞治疗的患者中出现了较高的心律失常事件,但6个月主要的心脏不良事件和室性心律失常的发生率并没有显著差异。 其他的临床试验也在展开,有研究者通过用导管来给缺血性心力衰竭患者注射骨骼肌成肌细胞。例如1篇关于经皮冠状动脉移植自体骨骼肌成肌细胞治疗心肌梗死心肌收缩力损伤的小型(10例患者,其中1例未能完成手术)Ⅰ期临床研究报道结果显示[21],6个月随访发现所有患者的心功能分级(NYHA)改善,9例患者中有6例患者的左心室射血分数提高3%-8%。Povsic等[22]进行了经导管向心肌移植成肌细胞治疗心力衰竭的研究,采用双盲、随机、安慰剂对照及多中心共同参与,从23例患者中得到的初步结果发现,该方法能够提高6 min步行距离但增加持续性室性心动过速的发生(15例患者中出现了7例)。 其他类似研究结果显示,10例患有扩张型心肌病的男性患者经皮注射自体成肌细胞,1年后NYHA 心功能分级从2.7±0.5下降至1.9±0.5 (P < 0.01)。在低剂量多巴胺丁酚输液时,成肌细胞注射区峰值收缩速度从(7.7±2.1 ) cm/s升高至(8.6±1.8) cm/s,P=0.02;左心室射血分数从(40±9)%提高至(46±8)%,且收缩末期容量从(56±28) mL/m2减少至(50±25) mL/m2[23-24]。但是,在先前的研究中,左心室功能的改善只在多巴酚丁胺输液过程中有记录。 缺血性心肌病患者心肌内注射成肌细胞的长期作用方面,已经开展了4项临床研究进行评估[25-28]。尽管其中3项显示心脏功能得到改善,但都在成肌细胞移植的同时还进行了冠状动脉旁路移植术或左心室辅助设备的安置,使结果的说明变得复杂。在第4项研究中,随访4年整体或局部都没有左心室功能的改善,这与另一份研究报道结果一致[29]。在这项研究中,成肌细胞治疗后6个月显示6 min步行距离增加,但没有出现左室射血分数的改善。大量小规模的骨骼肌成肌细胞临床治疗都产生了鼓舞人心的结果,但至今没有大规模的临床研究进一步证实这些结论。 2.2 间充质干细胞 间充质干细胞是一类具有高度可塑性的多能干细胞,在不同的诱导条件能够分化成为不同的组织细胞,例如骨组织细胞、脂肪组织细胞、软骨组织细胞等[30-35],因此间充质干细胞在临床治疗具有广阔的应用前景。 2.2.1 骨髓间充质干细胞 骨髓间充质干细胞又叫骨髓基质细胞,是一类具有多潜能和贴壁培养属性的非造血干细胞。骨髓间充质干细胞能够分化成软骨细胞、脂肪细胞、成骨细胞和骨骼肌细胞,另外有报道称可以分化成心肌细胞和内皮细胞[36-37],但这些心源性的潜能还有争议[38]。 通过对慢性心力衰竭动物模型给予骨髓间充质干细胞得到了鼓舞人心的结果。使用Ameroid闭合器建立的狗缺血性心力衰竭模型心外膜注射异体骨髓间充质干细胞,骨髓间充质干细胞分化成了平滑肌细胞和内皮细胞,增加了血管分布,并且改善了心肌功能[39]。类似的,在猪缺血性心肌病模型心肌梗死瘢痕区注射自体骨髓间充质干细胞后减小了梗死面积[40]。 根据这些有前景的动物实验结果,研究人员开展了一系列临床试验用于评估骨髓间充质干细胞临床应用的安全性及有效性[41]。Assmus 等[42]开展了一项双盲、安慰剂对照的多中心试验,204例成功再灌注的急性心肌梗死患者随机接受骨髓间充质干细胞或安慰剂,追踪观察发现,术后2年内主要心血管事件发生率下降。Kang等[43]围绕骨髓间充质干细胞治疗急性心肌梗死开展了一项回顾分析,最终纳入517例患者进入试验,结果表明骨髓间充质干细胞治疗心肌梗死是安全可行的,同时能够改善左心室射血分数。Chen等[44]开展了一项随机对照试验,将69例急性心肌梗死患者分为试验组及对照组,试验组经冠状动脉注射(48-60)×106个自体骨髓间充质干细胞,试验结果显示骨髓间充质干细胞可以显著提高急性心肌梗死患者的左室射血分数。 虽然骨髓间充质干细胞用于心力衰竭的安全性及有效性已得到证实,但自体及异体来源骨髓间充质干细胞间没有进行过比较,为此Hare等[45]开展了一项随机先导性实验,研究人员比较了3种不同剂量的自体骨髓间充质干细胞及异体骨髓间充质干细胞对缺血性心力衰竭患者的影响,最终结果显示各组严重不良反应事件发生率均保持在较低水平,骨髓间充质干细胞注射对患者的心脏功能、生活质量及心肌再生均具有良好作用。 尽管多数试验的结果都是振奋人心的,但仍然缺乏大量的临床数据,因此,需要继续开展多中心、大样本、随机双盲对照研究,结合更先进的影像学检查技术,并进行长期随访后做出骨髓间充质干细胞移植疗效的最后评定。 2.2.2 脂肪间充质干细胞 2001年Zuk等[46]从人脂肪组织提取物中分离出脂肪间充质干细胞。相较于其他来源的干细胞,脂肪干细胞来源广泛、免疫原性较低、对个体伤害较小。Perin等[47]开展的PRECISE临床研究,通过对127例患者进行临床试验后发现脂肪来源间充质干细胞可以稳定梗死面积以及改善最大耗氧量。Houtgraaf等[48]对14例ST段抬高型心肌梗死患者急性期进行冠状动脉内注射自体白色脂肪来源间充质干细胞(WT-hADMSCs)治疗,移植后6个月,与安慰剂组相比,脂肪来源间充质干细胞组左心室射血分数增加,梗死面积显著减少,且梗死区充盈缺损面积有明显改善。Qayyum等[49]针对慢性缺血性心脏病开展的一项临床研究表明,VEGF-A165刺激后的人脂肪来源间充质干细胞更能有效地改善心肌灌注和运动功能,并减少患者心肌缺血症状。 目前脂肪间充质干细胞治疗心力衰竭方面的研究虽然取得了可喜进展,但还有许多问题有待进一步研究和探讨,比如给药剂量、给药方式、不良反应、治疗机制等。 2.2.3 人脐血间充质干细胞 人脐血间充质干细胞是一种具有多向分化潜能的细胞,可以分化为多种组织细胞,包括骨、软骨、皮肤、神经元及神经胶质细胞等,与骨髓干细胞、胚胎干细胞及骨骼肌成肌细胞等干细胞相比,具有来源丰富、易收集及低温保存、受胎盘屏障保护污染率低、增殖分化能力强、免疫原性低、收集脐带对母体及胎儿无不利影响等优势,为治疗心力衰竭提供了全新的方向[50-51]。 国内一项研究将80例心力衰竭患者随机分为两组:对照组给予心力衰竭标准治疗;治疗组给予心力衰竭标准治疗+人脐血间充质干细胞静脉输注;平均随访24个月,观察治疗期间各组患者临床疗效、预后、再住院率、心功能指标及B型脑钠肽水平的变化。结果显示治疗期间对照组有10例死亡,治疗组有6例死亡;治疗组再住院率较对照组明显降低,治疗组有效率较对照组明显提高;治疗组心功能指标左室射血分数较治疗前明显升高,左心室收缩期末内径、左心室舒张期末内径及B型脑钠肽水平均较治疗前明显降低;且治疗组治疗后上述指标较对照组同期明显改善。提示人脐血间充质干细胞静脉移植治疗心力衰竭疗效显著[52]。 李雅娇[53]通过对比单纯经皮冠状动脉介入治疗急性心肌梗死和经皮冠状动脉介入治疗同时移植脐血间充质干细胞的疗效发现:脐血间充质干细胞组术后90 d的左心室射血分数持续改善,与术后7 d及对照组之间差异有显著性意义。脐血间充质干细胞组术后90 d SPECT测定的心肌灌注缺损面积显著低于术后7 d及对照组。表明经冠状动脉介入治疗同时移植脐血间充质干细胞可以显著改善急性心肌梗死患者的心室功能,心肌核素显像存活心肌明显增加。 2.3 心脏干细胞 2002 年,Hierlihy等[54]报道了心脏组织中有一群具有自我更新及多向分化能力的干细胞,并命名为心脏干细胞,推翻了心肌细胞不能再生的观念。心脏干细胞因其具有组织特异性和专一性,在用于心脏再生治疗中更具优势。 过去的10年中,进行了各种临床前急性心肌梗死动物模型实验,说明人和啮齿动物心脏干细胞可以减轻左心室功能紊乱和重构,还能促进再生。有证据表明缺血性心肌病与功能性心脏干细胞缺失有关[55],这激起研究心脏干细胞在慢性心力衰竭中作用的热情。 Makkar等[56]开展了一项Ⅰ期临床试验,将自体心脏干细胞经冠状动脉输入20例缺血性心肌病患者,在心脏干细胞输注4个月后左室射血分数从输注前的(29.0±1.7)%增加到(36.0±2.5)%。而对照组13例患者的左室射血分数则没有任何改变。心脏干细胞的有效作用一直持续着且更加明显(1年后左室射血分数:+8.1%,n=17;2年后,左室射血分数+12.9%,n=8)。在接受心脏干细胞治疗的9例患者中,通过核磁共振成像可以发现梗死面积明显减小。试验结果说明冠状动脉注射自体心脏干细胞能够有效提高心力衰竭患者的左心室收缩功能及心肌梗死面积。但SCIPIO是一项小规模的随机公开标签试验,带有较强的主观性,其试验结果还需要进一步验证。 2.4 成体干细胞治疗心力衰竭的主要机制 目前大多数的研究结果均表明成体干细胞可以用于改善心力衰竭患者的心脏功能,但是其作用机制仍不明确,但也有研究者提出假设:①干细胞具有多向分化潜能,移植的细胞分化成心脏细胞是可能发生的,关键的问题是这种现象的发生与功能改善是否成比例。从过往的研究结果来看,因移植细胞分化成心脏细胞而发生功效的例子只占了很小一部分;②移植细胞生成新血管[57-58]:在某些缺血性心脏病患者身上,新血管的生成可以改善心脏功能,但对于本身并不存在冠状动脉血流受限的患者来说,形成新血管这一理论就很难成立;③旁分泌机制:移植的细胞通过释放细胞因子、趋化因子、生长因子、外泌体或微粒到周围组织中来诱导心脏修复。这主要是通过释放的信号启动修复程序,包括内源性心脏干细胞的活化、新血管生成、凋亡抑制、肥大抑制及细胞外基质的有益改变。这些共同的作用使得左心室功能强化,改善再灌注及心脏修复[59];④细胞融合:在2004年,自发细胞融合作为可变机制被提出,通过这个机制移植的骨髓细胞可使得成体组织明显再生。但是细胞融机制的观点近年来的支持者正在减少[60]。"
[1] Heidenreich PA, Albert NM, Allen LA, et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013; 6(3):606-619.[2] Lerman DA, Alotti N, Ume KL, et al. Cardiac Repair and Regeneration: The Value of Cell Therapies. Eur Cardiol. 2016; 11(1):43-48.[3] 黄峻. 中国心力衰竭流行病学特点和防治策略[J]. 中华心脏与心律电子杂志, 2015(2):81-82.[4] Brenner H, Bouvier AM, Foschi R, et al. Progress in colorectal cancer survival in Europe from the late 1980s to the early 21st century: the EUROCARE study. Int J Cancer. 2012;131(7): 1649-1658.[5] Coleman MP, Forman D, Bryant H, et al. Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data. Lancet. 2011;377(9760):127-138.[6] Siegel R, DeSantis C, Virgo K, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62(4): 220-241.[7] Soldner F, Hockemeyer D, Beard C, et al. Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell. 2009;136(5):964-977. [8] Kaji K, Norrby K, Paca A,et al. Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature. 2009;458(7239):771-775.[9] Riggs JW, Barrilleaux BL, Varlakhanova N, et al. Induced pluripotency and oncogenic transformation are related processes. Stem Cells Dev. 2013;22(1):37-50.[10] Ma T, Xie M, Laurent T, et al. Progress in the reprogramming of somatic cells. Circ Res. 2013;112(3):562-574.[11] Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145-1147.[12] Cao F, Lin S, Xie X, et al. In vivo visualization of embryonic stem cell survival, proliferation, and migration after cardiac delivery. Circulation. 2006;113(7):1005-1014.[13] Fukuda H, Takahashi J, Watanabe K, et al. Fluorescence-activated cell sorting-based purification of embryonic stem cell-derived neural precursors averts tumor formation after transplantation. Stem Cells. 2006;24(3): 763-771.[14] Buckingham M, Montarras D. Skeletal muscle stem cells. Curr Opin Genet Dev. 2008;18(4):330-336.[15] Chachques JC, Acar C, Herreros J, et al. Cellular cardiomyoplasty: clinical application. Ann Thorac Surg. 2004;77(3):1121-1130.[16] Murry CE, Wiseman RW, Schwartz SM, et al. Skeletal myoblast transplantation for repair of myocardial necrosis. J Clin Invest. 1996;98(11):2512-2523.[17] Menasché P, Hagège AA, Vilquin JT, et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol. 2003;41(7): 1078-1083.[18] Reinecke H, MacDonald GH, Hauschka SD, et al. Electromechanical coupling between skeletal and cardiac muscle. Implications for infarct repair. J Cell Biol. 2000; 149(3):731-740.[19] Herreros J, Prósper F, Perez A, et al. Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction. Eur Heart J. 2003;24(22):2012-2020.[20] Menasché P, Alfieri O, Janssens S, et al. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation. 2008;117(9):1189-1200.[21] Siminiak T, Fiszer D, Jerzykowska O, et al. Percutaneous trans-coronary-venous transplantation of autologous skeletal myoblasts in the treatment of post-infarction myocardial contractility impairment: the POZNAN trial. Eur Heart J. 2005;26(12):1188-1195.[22] Povsic TJ, O'Connor CM, Henry T, et al. A double-blind, randomized, controlled, multicenter study to assess the safety and cardiovascular effects of skeletal myoblast implantation by catheter delivery in patients with chronic heart failure after myocardial infarction. Am Heart J. 2011;162(4):654-662.e1.[23] Biagini E, Valgimigli M, Smits PC, et al. Stress and tissue Doppler echocardiographic evidence of effectiveness of myoblast transplantation in patients with ischaemic heart failure.Eur J Heart Fail. 2006;8(6):641-648.[24] Dib N, Dinsmore J, Lababidi Z, et al. One-year follow-up of feasibility and safety of the first U.S., randomized, controlled study using 3-dimensional guided catheter-based delivery of autologous skeletal myoblasts for ischemic cardiomyopathy (CAuSMIC study). JACC Cardiovasc Interv. 2009;2(1):9-16.[25] Dib N, Michler RE, Pagani FD, et al. Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up. Circulation. 2005;112(12):1748-1755.[26] Hagège AA, Marolleau JP, Vilquin JT, et al. Skeletal myoblast transplantation in ischemic heart failure: long-term follow-up of the first phase I cohort of patients. Circulation. 2006;114(1 Suppl):I108-113.[27] Gavira JJ, Herreros J, Perez A, et al. Autologous skeletal myoblast transplantation in patients with nonacute myocardial infarction: 1-year follow-up. J Thorac Cardiovasc Surg. 2006;131(4):799-804.[28] Veltman CE, Soliman OI, Geleijnse ML, et al. Four-year follow-up of treatment with intramyocardial skeletal myoblasts injection in patients with ischaemic cardiomyopathy. Eur Heart J. 2008;29(11):1386-1396.[29] Duckers HJ, Houtgraaf J, Hehrlein C, et al. Final results of a phase IIa, randomised, open-label trial to evaluate the percutaneous intramyocardial transplantation of autologous skeletal myoblasts in congestive heart failure patients: the SEISMIC trial. EuroIntervention. 2011;6(7):805-812.[30] 李焕萍,刘春蓉,张永亮.骨髓间充质干细胞在医学领域中的研究与应用[J].中国组织工程研究与临床康复, 2007,11(28): 5622-5625.[31] 胡资兵,曾荣,郭伟韬,等.骨髓间充质干细胞诱导分化特征[J].中国组织工程研究与临床康复, 2008,12(43): 8561-8566.[32] Woodbury D, Reynolds K, Black IB. Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. J Neurosci Res. 2002;69(6):908-917.[33] 孙伟,胡亮,赵兴,等.体外定向诱导小鼠骨髓间充质干细胞分化为神经元样细胞[J].安徽农业学报,2010,38(7):3492-3530.[34] 邓方阁,张秀英,王心蕊,等.体外模拟心肌微环境中人骨髓间充质干细胞向心肌细胞的分化[J].吉林大学学报,2007,33(2): 257-259.[35] 鲁学恒,马力,刘沛.体外诱导大鼠骨髓间充质干细胞向肝细胞分化的实验研究[J].中国医科大学学报,2007,36(3):256-258.[36] Toma C, Pittenger MF, Cahill KS, et al. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation. 2002;105(1):93-98.[37] Reyes M, Dudek A, Jahagirdar B, et al. Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest. 2002;109(3):337-346.[38] Reinecke H, Minami E, Zhu WZ, et al. Cardiogenic differentiation and transdifferentiation of progenitor cells. Circ Res. 2008;103(10):1058-1071.[39] Silva GV, Litovsky S, Assad JA, et al. Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation. 2005;111(2):150-156.[40] Schuleri KH, Feigenbaum GS, Centola M, et al. Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. Eur Heart J. 2009;30(22): 2722-2732.[41] Perin EC, Silva GV, Henry TD, et al. A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF). Am Heart J. 2011;161(6):1078-1087.e3.[42] Assmus B, Rolf A, Erbs S, et al. Clinical outcome 2 years after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction. Circ Heart Fail. 2010;3(1):89-96.[43] Kang S, Yang YJ, Li CJ, et al. Effects of intracoronary autologous bone marrow cells on left ventricular function in acute myocardial infarction: a systematic review and meta-analysis for randomized controlled trials. Coron Artery Dis. 2008;19(5):327-335.[44] Chen SL, Fang WW, Ye F, et al. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol. 2004;94(1):92-95.[45] Hare JM, Fishman JE, Gerstenblith G, et al. Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA. 2012;308(22):2369-2379.[46] Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12): 4279-4295.[47] Perin EC, Sanchez PL, Ruiz RS, et al. First in man transendocardial injection of autologous adipose-derived stem cells in patients with non revascularizable ischemic myocardium (precise). Circulation. 2010;122: A17966.[48] Houtgraaf JH, den Dekker WK, van Dalen BM, et al. First experience in humans using adipose tissue-derived regenerative cells in the treatment of patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2012;59(5):539-540.[49] Qayyum AA, Haack-Sørensen M, Mathiasen AB, et al. Adipose-derived mesenchymal stromal cells for chronic myocardial ischemia (MyStromalCell Trial): study design. Regen Med. 2012;7(3):421-428.[50] Timmers L, Lim SK, Arslan F, et al. Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. Stem Cell Res. 2007;1(2):129-137.[51] Perin EC, Geng YJ, Willerson JT. Adult stem cell therapy in perspective. Circulation. 2003;107(7):935-938.[52] 杨冰冰,张素荣.人脐血间充质干细胞移植治疗心力衰竭的临床疗效观察[J]. 中国现代医生,2016,54(3):20-23,27.[53] 李雅娇. 人脐血间充质干细胞治疗急性心肌梗死的研究[J]. 中国民族民间医药, 2013,22(11):106-107.[54] Hierlihy AM, Seale P, Lobe CG, et al. The post-natal heart contains a myocardial stem cell population. FEBS Lett. 2002;530(1-3):239-243.[55] Urbanek K, Torella D, Sheikh F, et al. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci U S A. 2005;102(24): 8692-8697.[56] Makkar RR, Smith RR, Cheng K, et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet. 2012;379(9819):895-904.[57] Cai L, Johnstone BH, Cook TG, et al. IFATS collection: Human adipose tissue-derived stem cells induce angiogenesis and nerve sprouting following myocardial infarction, in conjunction with potent preservation of cardiac function. Stem Cells. 2009;27(1):230-237.[58] Wang J, Zhang S, Rabinovich B, et al. Human CD34+ cells in experimental myocardial infarction: long-term survival, sustained functional improvement, and mechanism of action. Circ Res. 2010;106(12):1904-1911.[59] Gnecchi M, Zhang Z, Ni A, et al. Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res. 2008;103(11): 1204-1219.[60] Murry CE, Soonpaa MH, Reinecke H, et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature. 2004;428(6983):664-668.[61] Konoplyannikov M, Kalsin V, Averyanov A, et al. Stem Cell Therapy of Ischemic Heart Disease. Journal of Biomedical Science & Engineering. 2016; 9(4):191-215. |
[1] | Li Xuan, Sun Yimin, Li Longbiao, Wang Zhenming, Yang Jing, Wang Chenglin, Ye Ling. Manufacturing of nano-modified polycaprolactone microspheres and its biological effects in dental pulp cells [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(10): 1602-1608. |
[2] | Liu Xiaogang, Li Tian, Zhang Duo. Effect and mechanism of the effective components of Chinese medicine on promoting the differentiation of bone marrow mesenchymal stem cells into chondrocytes [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(1): 121-126. |
[3] | Lin Miaoyuan, Li Yuwan, Liu Yi, Chen Bei, Zhang Li. Research hotspots and application value of tissue-engineered skin [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(1): 159-166. |
[4] | Xie Xingqi, Hu Wei, Tu Guanjun. Bone marrow mesenchymal stem cells-derived exosomes combined with chondroitinase ABC for treating spinal cord injury in rats [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(1): 20-26. |
[5] | Yang Tengyun, Li Yanlin, Liu Dejian, Wang Guoliang, Zheng Zhujun. Chondrogenic differentiation of peripheral blood-derived mesenchymal stem cells induced by transforming growth factor beta 3: a dose-effect relationship [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(1): 45-51. |
[6] | Jing Jin, Zhao Shandi, Chen Long, Peng Shuanglin, Tang Hui, Guo Daijin, Zeng Xinyi, Xiao Jingang. Repair of calvarial defects in osteoporotic mice by adipose-derived stem cells combined with biphasic calcium phosphate ceramic scaffold [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(1): 90-95. |
[7] | Kang Yue, Liu Jie. Biological function of circular RNAs in osteogenic differentiation of mesenchymal stem cells [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(1): 107-112. |
[8] | Zhang Tongtong, Wang Zhonghua, Wen Jie, Song Yuxin, Liu Lin. Application of three-dimensional printing model in surgical resection and reconstruction of cervical tumor [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(9): 1335-1339. |
[9] | Zeng Yanhua, Hao Yanlei. In vitro culture and purification of Schwann cells: a systematic review [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(7): 1135-1141. |
[10] | Xu Dongzi, Zhang Ting, Ouyang Zhaolian. The global competitive situation of cardiac tissue engineering based on patent analysis [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(5): 807-812. |
[11] | Wu Zijian, Hu Zhaoduan, Xie Youqiong, Wang Feng, Li Jia, Li Bocun, Cai Guowei, Peng Rui. Three-dimensional printing technology and bone tissue engineering research: literature metrology and visual analysis of research hotspots [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(4): 564-569. |
[12] | Chang Wenliao, Zhao Jie, Sun Xiaoliang, Wang Kun, Wu Guofeng, Zhou Jian, Li Shuxiang, Sun Han. Material selection, theoretical design and biomimetic function of artificial periosteum [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(4): 600-606. |
[13] | Liu Fei, Cui Yutao, Liu He. Advantages and problems of local antibiotic delivery system in the treatment of osteomyelitis [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(4): 614-620. |
[14] | Li Xiaozhuang, Duan Hao, Wang Weizhou, Tang Zhihong, Wang Yanghao, He Fei. Application of bone tissue engineering materials in the treatment of bone defect diseases in vivo [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(4): 626-631. |
[15] | Zhang Zhenkun, Li Zhe, Li Ya, Wang Yingying, Wang Yaping, Zhou Xinkui, Ma Shanshan, Guan Fangxia. Application of alginate based hydrogels/dressings in wound healing: sustained, dynamic and sequential release [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(4): 638-643. |
Viewed | ||||||
Full text |
|
|||||
Abstract |
|
|||||