切换至 "中华医学电子期刊资源库"

中华细胞与干细胞杂志(电子版) ›› 2019, Vol. 09 ›› Issue (02) : 119 -123. doi: 10.3877/cma.j.issn.2095-1221.2019.02.009

综述

心血管前体细胞诱导、增殖、分化及应用研究进展
江徐1, 王永煜1,()   
  1. 1. 325035 温州医科大学基础医学院
  • 收稿日期:2018-11-25 出版日期:2019-04-01
  • 通信作者: 王永煜
  • 基金资助:
    国家自然科学基金资助项目(81670454)

Progress on cardiovascular progenitor cell induction, proliferation, differentiation and applications

Xu Jiang1, Yongyu Wang1,()   

  1. 1. College of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China
  • Received:2018-11-25 Published:2019-04-01
  • Corresponding author: Yongyu Wang
引用本文:

江徐, 王永煜. 心血管前体细胞诱导、增殖、分化及应用研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2019, 09(02): 119-123.

Xu Jiang, Yongyu Wang. Progress on cardiovascular progenitor cell induction, proliferation, differentiation and applications[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2019, 09(02): 119-123.

心血管前体细胞(CPCs)是指在胚胎发育过程或成体组织中存在的一类能够定向分化为心肌细胞(CMs)、内皮细胞(ECs)和血管平滑肌细胞(VSMCs)等具有特定分化潜能的前体细胞。应用多能干细胞(PSCs)定向诱导分化技术亦可在体外直接获得CPCs。CPCs不仅可为研究心血管细胞分化的分子机制提供细胞模型,而且还可以为其在再生医学研究及应用中提供大量的种子细胞来源。然而,人们对CPCs的诱导,自我更新及分化的调控机制仍知之甚少,因此,只有较全面地认识CPCs的各种生物学特性,才能在科研和临床中充分利用它们。本综述将重点阐述PSCs来源的CPCs的各种标志物及其诱导、增殖和定向分化为心血管细胞的相关信号调控机制及其在心血管疾病治疗应用中的最新进展,以期深入了解CPCs的生物学特性并为其在心血管再生医学中的应用提供理论基础。

Cardiovascular progenitor cells (CPCs) are multipotent stem cells with differentiation potential into cardiomyocytes (CMs), endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) during embryonic development or in adult tissues. The application of pluripotent stem cells (PSCs) directed differentiation technology can also directly obtain CPCs in vitro. CPCs could not only provide a cell model for studying the molecular mechanism of differentiation of cardiovascular cells, but also a promising cell resource for cardiovascular regeneration. However, the mechanisms of induction, self-renewal and differentiation of CPCs are still incompletely understood, which limited their applications in cardiovascular cell therapy. This review will focus on the various markers of CPCs and the signaling regulation on CPCs induction, proliferation, differentiation, as well as the applications in cardiovascular regeneration.

图1 CPCs的作用及调控注:CPCs可以衍生自hESCs或通过体细胞直接转分化产生iPSCs而产生。FGF,经典Wnt,IGF- PI3K等信号可促进CPC的增殖。CPCs扩增后,可将其直接植入心脏或用于生成组织工程移植物,疾病模型、药物筛选、毒性测试等。在不同信号的诱导下,能够定向分化为CMs、ECs和VSMCs。CPCs:心血管前体细胞;hESCs:人胚胎干细胞;iPSCs:诱导多能干细胞;CMs:心肌细胞;ECs:内皮细胞;VSMCs:血管平滑肌细胞
34
Barile L, Milano G, Vassalli G. Beneficial effects of exosomes secreted by cardiac-derived progenitor cells and other cell types in myocardial ischemia[J]. Stem Cell Investig, 2017, 4:93.
35
Menasche P, Vanneaux V, Hagege A, et al. Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report[J]. Eur Heart J, 2015, 36(30):2011-2017.
36
Menasché P, Vanneaux V, Hagège A, et al. Transplantation of human embryonic stem cell-derived cardiovascular progenitors for severe ischemic left ventricular dysfunction[J]. J Am Coll Cardiol, 2018, 71(4):429-438.
37
Trac D, Xu CH, Davis ME. Aggregation of child cardiac progenitor cells into spheres activates notch signaling and improves treatment of right ventricular heart failure[J]. Circulation, 2017, 136(1):526-538.
1
Birket MJ, Mummery CL. Pluripotent stem cell derived cardiovascular progenitors-A developmental perspective[J]. Dev Biol, 2015, 400(2):169-179.
2
Le T, Chong J. Cardiac progenitor cells for heart repair[J]. Cell Death Discov, 2016, 2:16052.
3
Zhou B, Wu SM. Reassessment of c-Kit in cardiac cells a complex interplay between expression, fate, and function[J]. Circ Res, 2018, 123(1):9-11.
4
Maliken BD, Molkentin JD. Undeniable evidence that the adult mammalian heart lacks an endogenous regen-erative stem cell[J]. Circulation, 2018, 138(8):806-808.
5
Waring CD, Vicinanza C, Papalamprou AA, et al. The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation[J]. Eur Heart J, 2014, 35(39, SI):2722-2731.
6
Chiapparo G, Lin XH, Lescroart FA, et al. Mesp1 controls the speed, polarity, and directionality of cardiovascular progenitor migration[J]. J Cell Biol, 2016, 213(4):463-477.
7
Bondue A, Tännler S, Chiapparo G, et al. Defining the earliest step of cardiovascular progenitor specification during embryonic stem cell differentiation[J]. J Cell Biol, 2011, 192(5):751-765.
8
Den Hartogh SC, Schreurs C, Monshouwer-Kloots JJ, et al. Dual reporter MESP1(mCherry/w)-NKX2-5 (eGFP/w) hESCs enable studying early human cardiac differentiation[J]. Stem Cells, 2015, 33(1):56-67.
9
Wu SM, Fujiwara Y, Cibulsky SM, et al. Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart[J]. Cell, 2006, 127(6):1137-1150.
10
Watanabe Y, Zaffran S, Kuroiwa A, et al. Fibroblast growth factor 10 gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic Switch for down-regulation in the myocardium[J]. Proc Natl Acad Sci U S A, 2012, 109(45):18273-18280.
11
Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration[J]. Cell, 2003, 114(6):763-776.
12
Nadal-Ginard B, Ellison GM, Torella D. Absence of evidence is not evidence of absence pitfalls of cre knock-ins in the c-Kit locus[J]. Circ Res, 2014, 115(4):415-418.
13
van Berlo JH, Kanisicak O, Maillet M, et al. C-kit(+) cells minimally contribute cardiomyocytes to the heart[J]. Nature, 2014, 509(7500): 337-341.
14
Sultana N, Zhang L, Yan J, et al. Resident c-kit(+) cells in the heart are not cardiac stem cells[J]. Nat Commun, 2015, 6:8701.
15
Liu QZ, Yang R, Huang XZ, et al. Genetic lineage tracing identifies in situ Kit-expressing cardiomyocytes[J]. Cell Res, 2016, 26(1):119-130.
16
He L, Li Y, Li Y, et al. Enhancing the precision of genetic lineage tracing using dual recombinases[J]. Nat Med, 2017, 23(12):1488-1498.
17
Yoon C, Song H, Yin T, et al. FZD4 marks lateral plate mesoderm and signals with NORRIN to increase cardiomyocyte induction from pluripotent stem Cell-Derived cardiac progenitors[J]. Stem Cell Reports, 2018, 10(1):87-100.
18
Skelton RJ, Brady B, Khoja S, et al. CD13 and ROR2 permit isolation of highly enriched cardiac mesoderm from differentiating human embryonic stem cells[J]. Stem Cell Reports, 2016, 6(1):95-108.
19
Skelton RJ, Costa M, Anderson DJ, et al. SIRPA, VCAM1 and CD34 identify discrete lineages during early human cardiovascular development[J]. Stem Cell Res, 2014, 13(1):172-179.
20
Noseda M, Peterkin T, Simões FC, et al. Cardiopoietic factors: extracellular signals for cardiac lineage commitment[J]. Circ Res, 2011, 108(1): 129-152.
21
Cai WQ, Albini S, Wei K, et al. Coordinate nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment[J]. Genes Dev, 2013, 27(21):2332-2344.
22
Cao N, Liang H, Huang J, et al. Highly efficient induction and long-term maintenance of multipotent cardiovascular progenitors from human pluripotent stem cells under defined conditions[J]. Cell Res, 2013, 23(9):1119-1132.
23
Burridge PW, Keller G, Gold JD, et al. Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming[J]. Cell Stem Cell, 2012, 10(1):16-28.
24
Sirbu IO, Zhao X, Duester G. Retinoic acid controls heart anteroposterior patterning by down-regulating Isl1 through the Fgf8 pathway[J]. Dev Dyn, 2008, 237(6):1627-1635.
25
Novikov N, Evans T. Tmem88a mediates GATA-dependent specification of cardiomyocyte progenitors by restricting WNT signaling[J]. Development, 2013, 140(18):3787-3798.
26
Zhang Y, Cao N, Huang Y, et al. Expandable cardiovascular progenitor cells reprogrammed from fibroblasts[J]. Cell Stem Cell, 2016, 18(3): 368-381.
27
Birket MJ, Ribeiro MC, Verkerk AO, et al. Expansion and patterning of cardiovascular progenitors derived from human pluripotent stem cells [J]. Nat Biotechnol, 2015, 33(9):970-979.
28
Lalit PA, Salick MR, Nelson DO, et al. Lineage reprogramming of fibroblasts into proliferative induced cardiac progenitor cells by defined factors[J]. Cell Stem Cell, 2016, 18(3):354-367.
29
Puente BN, Kimura W, Muralidhar SA, et al. The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response[J]. Cell, 2014, 157(3):565-579.
30
Wang WE, Li L, Xia X, et al. Dedifferentiation,proliferation and redifferentiation of adult mammalian cardio-myocytes after ischemic injury[J]. Circulation, 2017, 136(9):834-848.
31
Sinha S, Iyer D, Granata A. Embryonic origins of human vascular smooth muscle cells: implications for in vitro modeling and clinical application[J]. Cell Mol Life Sci, 2014, 71(12):2271-2288.
32
Liu Y, Chen L, Diaz AD, et al. Mesp1 marked cardiac progenitor cells repair infarcted mouse hearts[J]. Sci Rep, 2016, 6(1):1-14.
33
Zhu KY, Wu Q, Ni C, et al. Lack of remuscularization following transplantation of human embryonic stem cell-derived cardiovascular progenitor cells in infarcted nonhuman primates[J]. Circ Res, 2018, 122(7):958-969.
[1] 何羽. 腔镜微创手术治疗分化型甲状腺癌的研究进展[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(04): 456-458.
[2] 浦凌宵, 诸俊浩, 陶亮, 王峰, 王萌, 管文贤. 低黏附性胃癌PET/CT影像学特征和脂代谢相关机制研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(03): 255-260.
[3] 司钦亮, 毕世龙, 焦慧骁, 李世照, 陈哲禹, 武玉东. 精索去分化脂肪肉瘤两例并文献复习[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(06): 585-590.
[4] 杨攀, 黄晓寒, 邓才霞, 周利航, 周向东, 罗虎. SMARCA4缺失的胸部未分化肿瘤临床特征及预后分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(04): 529-534.
[5] 郝春艳, 吉泽, 成苏杭, 李文思, 王丹. 血清miR-155联合sCD14水平判断慢性阻塞性肺疾病预后的临床分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(01): 87-90.
[6] 任江波, 李丽, 王萍. 阻断PI3K/Akt信号通路促进低表达FoxA2肝脏前体细胞对分化诱导剂应答并朝肝细胞方向分化[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 336-343.
[7] 李彦浇, 梁雷, 金钫, 王智伟. 银杏内酯B通过调控miR-24-3p对人牙周膜干细胞增殖、成骨分化的影响[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(04): 229-235.
[8] 郭煦妍, 罗志嵘, 薛琦, 王林猛, 吉运华, 张波. 3D生物打印在肾脏再生领域的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(03): 181-185.
[9] 杨阳, 王琤, 周文土, 周冰. Caveolae/Caveolin-1与膜胆固醇共同调控小鼠BMSCs成骨分化[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(03): 137-142.
[10] 景水力, 王娟, 刘晔, 周亨, 熊威, 叶青松. 间充质干细胞在脊髓损伤中的应用及研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(02): 113-121.
[11] 乔树叶, 以敏, 李理, 潘思琼, 陈苗玉. 骨肉瘤诱导多能干细胞模型的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(01): 30-36.
[12] 刘娟丽, 马四清, 乌仁塔娜. 髓源性抑制细胞在脓毒症中的研究进展[J/OL]. 中华重症医学电子杂志, 2024, 10(03): 271-278.
[13] 张津, 李欣达, 徐如祥. 神经类器官在大脑常见疾病治疗中的应用及在脊髓损伤修复中的应用前景[J/OL]. 中华脑科疾病与康复杂志(电子版), 2024, 14(05): 257-263.
[14] 苑乐添, 王艺霖, 沈子剑, 闫呈新. 血清GDF15、sB7-H1联合多层螺旋CT灌注成像技术对胃癌患者淋巴结转移的诊断价值[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(01): 62-66.
[15] 杨菲, 刘腾飞, 赵志军, 李睿聪, 张颉, 刘妍, 赵珍. 血清维生素水平与分化型甲状腺癌的关联性研究[J/OL]. 中华临床医师杂志(电子版), 2024, 18(07): 633-640.
阅读次数
全文


摘要