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中华细胞与干细胞杂志(电子版) ›› 2022, Vol. 12 ›› Issue (04) : 224 -229. doi: 10.3877/cma.j.issn.2095-1221.2022.04.005

综述

心肌微组织的构建及其在心肌损伤修复中的研究进展
柯敏霞1, 杨黄恬1,()   
  1. 1. 200031 上海,中国科学院中国科学院大学上海营养与健康研究所肿瘤与微环境重点实验室分子心脏学研究组
  • 收稿日期:2022-04-11 出版日期:2022-08-01
  • 通信作者: 杨黄恬
  • 基金资助:
    国家重点研发计划专项项目(2017YFA 0103700); 中国科学院"器官重建与制造"战略性先导科技专项(XDA16010201); 国家自然科学基金(81520108004)

Advances in the construction of cardiac microtissues and its repair of infarcted hearts

Minxia Ke1, Huangtian Yang1,()   

  1. 1. CAS Key Laboratory of Tissue Microenvironment and Tumor, Laboratory of Molecular Cardiology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences (CAS), CAS, Shanghai 200031, China
  • Received:2022-04-11 Published:2022-08-01
  • Corresponding author: Huangtian Yang
引用本文:

柯敏霞, 杨黄恬. 心肌微组织的构建及其在心肌损伤修复中的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2022, 12(04): 224-229.

Minxia Ke, Huangtian Yang. Advances in the construction of cardiac microtissues and its repair of infarcted hearts[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2022, 12(04): 224-229.

心肌梗死(MI)及其导致的心力衰竭(HF)是疾病致死的主要原因,严重威胁人类健康。现有药物和介入治疗手段无法补偿MI引起的心肌细胞丢失这一导致HF的关键病理性改变。随着干细胞生物学、材料科学和工程技术的进展和整合,心肌微组织(CMTs)构建的探索成为心脏再生医学研究领域的新生长点。本文回顾CMTs构建的研究进展及对MI后损伤修复的作用,重点讨论CMTs的构建策略、在MI后心肌损伤修复中的移植方式和效果,并探讨CMTs用于缺血性心肌损伤修复需解决的问题。

Myocardial infarction (MI) and resulting heart failure (HF) are the leading causes of mortality worldwide. Current therapeutic approaches cannot compensate for irreversible loss of cardiomyocytes and damage of cardiocontractile myocardial that is hardly regenerated. Due to the integration of recent advances in stem cell biology, materials science, and engineering, cardiac microtissues (CMTs) provide a new direction and hope for cardiac regenerative medicine. This concise review summarized main research advances in the construction and application of CMTs for the repair of infarcted hearts, focusing on the construction strategy of CMTs, the transplantation approaches and effects in the promtion of cardial repair. The challenges for the translational applications of the CMTs in myocardial repair and regeneration were discussed too.

1
Anderson JL, Morrow DA. Acute myocardial infarction[J]. N Engl J Med, 2017, 376(21):2053-2064.
2
Shah KS, Kittleson MM, Kobashigawa JA. Updates on heart transplantation[J]. Curr Heart Fail Rep, 2019, 16(5):150-156.
3
Frigerio M. Left ventricular assist device: indication, timing, and management[J]. Heart Fail Clin, 2021, 17(4):619-634.
4
Bolli R, Solankhi M, Tang XL, et al. Cell therapy in patients with heart failure: a comprehensive review and emerging concepts[J]. Cardiovasc Res, 2022, 118(4):951-976.
5
Zhu K, 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.
6
Li Q, Wang J, Wu Q, et al. Perspective on human pluripotent stem cell-derived cardiomyocytes in heart disease modeling and repair[J]. Stem Cells Transl Med, 2020, 9(10):1121-1128.
7
Garbern JC, Lee RT. Heart regeneration: 20 years of progress and renewed optimism[J]. Dev Cell, 2022, 57(4):424-439.
8
Wu Q, Wang J, Tan WLW, et al. Extracellular vesicles from human embryonic stem cell-derived cardiovascular progenitor cells promote cardiac infarct healing through reducing cardiomyocyte death and promoting angiogenesis[J]. Cell Death Dis, 2020, 11(5):354.
9
Patino-Guerrero A, Veldhuizen J, Zhu W, et al. Three-dimensional scaffold-free microtissues engineered for cardiac repair[J]. J Mater Chem B, 2020, 8(34):7571-7590.
10
Boheler KR, Meli AC, Yang HT. Special issue on recent progress with hPSC-derived cardiovascular cells for organoids, engineered myocardium, drug discovery, disease models, and therapy[J]. Pflugers Arch, 2021, 473(7):983-988.
11
Bergmann O, Zdunek S, Felker A, et al. Dynamics of cell generation and turnover in the human heart[J]. Cell, 2015, 161(7):1566-1575.
12
Pinto AR, Ilinykh A, Ivey MJ, et al. Revisiting cardiac cellular composition[J]. Circ Res, 2016, 118(3):400-409.
13
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.
14
Burridge PW, Matsa E, Shukla P, et al. Chemically defined generation of human cardiomyocytes[J]. Nat Methods, 2014, 11(8):855-860.
15
Patsch C, Challet-Meylan L, Thoma EC, et al. Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells[J]. Nat Cell Biol, 2015, 17(8):994-1003.
16
Bao X, Lian X, Qian T, et al. Directed differentiation and long-term maintenance of epicardial cells derived from human pluripotent stem cells under fully defined conditions[J]. Nat Protoc, 2017, 12(9):1890-1900.
17
Luo XL, Zhang P, Liu X, et al. Myosin light chain 2 marks differentiating ventricular cardiomyocytes derived from human embryonic stem cells[J]. Pflugers Arch, 2021, 473(7):991-1007.
18
Giacomelli E, Meraviglia V, Campostrini G, et al. Human-iPSC-derived cardiac stromal cells enhance maturation in 3D cardiac microtissues and reveal non-cardiomyocyte contributions to heart disease[J]. Cell Stem Cell, 2020, 26(6):862-879.e11.
19
Campostrini G, Meraviglia V, Giacomelli E, et al. Generation, functional analysis and applications of isogenic three-dimensional self-aggregating cardiac microtissues from human pluripotent stem cells[J]. Nat Protoc, 2021, 16(4):2213-2256.
20
Liu Y, Zhang Y, Mei T, et al. hESCs-derived early vascular cell spheroids for cardiac tissue vascular engineering and myocardial infarction treatment[J]. Adv Sci (Weinh), 2022, 9(9):e2104299. doi: 10.1002/advs.202104299.
21
Bargehr J, Ong LP, Colzani M, et al. Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration[J]. Nat Biotechnol, 2019, 37(8):895-906.
22
Gao L, Gregorich ZR, Zhu W, et al. Large cardiac muscle patches engineered from human induced-pluripotent stem cell-derived cardiac cells improve recovery from myocardial infarction in swine[J]. Circulation, 2018, 137(16):1712-1730.
23
Cho S, Lee C, Skylar-Scott MA, et al. Reconstructing the heart using iPSCs: engineering strategies and applications[J]. J Mol Cell Cardiol, 2021, 157:56-65.
24
Wendel JS, Ye L, Tao R, et al. Functional effects of a tissue-engineered cardiac patch from human induced pluripotent stem cell-derived cardiomyocytes in a rat infarct model[J]. Stem Cells Transl Med, 2015, 4(11):1324-1332.
25
Querdel E, Reinsch M, Castro L, et al. Human engineered heart tissue patches remuscularize the injured heart in a dose-dependent manner[J]. Circulation, 2021, 143(20):1991-2006.
26
Kaiser NJ, Kant RJ, Minor AJ, et al. Optimizing blended collagen-fibrin hydrogels for cardiac tissue engineering with human iPSC-derived cardiomyocytes[J]. ACS Biomater Sci Eng, 2019, 5(2):887-899.
27
Riegler J, Tiburcy M, Ebert A, et al. Human engineered heart muscles engraft and survive long term in a rodent myocardial infarction model[J]. Circ Res, 2015, 117(8):720-730.
28
Qin X, Riegler J, Tiburcy M, et al. Magnetic resonance imaging of cardiac strain pattern following transplantation of human tissue engineered heart muscles[J]. Circ Cardiovasc Imaging, 2016, 9(11):e004731. doi: 10.1161/CIRCIMAGING.116.004731.
29
Tsui JH, Ostrovsky-Snider NA, Yama DMP, et al. Conductive silk-polypyrrole composite scaffolds with bioinspirednanotopographic cues for cardiac tissue engineering[J]. J Mater Chem B, 2018, 6(44):7185-7196.
30
Liang Y, Mitriashkin A, Lim TT, et al. Conductive polypyrrole-encapsulated silk fibroin fibers for cardiac tissue engineering[J]. Biomaterials, 2021, 276:121008. doi: 10.1016/j.biomaterials.2021.121008.
31
Bouhrira N, Galie PA, Janmey PA. Hyaluronan disrupts cardiomyocyte organization within 3D fibrin-based hydrogels[J]. Biophys J, 2019, 116(7):1340-1347.
32
Saporito F, Sandri G, Bonferoni MC, et al. Electrospun gelatin(-)chondroitin sulfate scaffolds loaded with platelet lysate promote immature cardiomyocyte proliferation[J]. Polymers (Basel), 2018, 10(2):208. doi: 10.3390/polym10020208.
33
Chu X, Wang M, Qiu X, et al. Strategies for constructing pluripotent stem cell- and progenitor cell-derived three-dimensional cardiac micro-tissues[J]. J Biomed Mater Res A, 2022, 110(2):488-503.
34
Maiullari F, Costantini M, Milan M, et al. A multi-cellular 3D bioprinting approach for vascularized heart tissue engineering based on HUVECs and iPSC-derived cardiomyocytes[J]. Sci Rep, 2018, 8(1):13532. doi: 10.1038/s41598-018-31848-x.
35
Chen Y, Wang J, Shen B, et al. Engineering a freestanding biomimetic cardiac patch using biodegradable poly (lactic-co-glycolic acid) (PLGA) and human embryonic stem cell-derived ventricular cardiomyocytes (hESC-VCMs)[J]. Macromol Biosci, 2015, 15(3):426-436.
36
Brazhkina O, Park JH, Park HJ, et al. Designing a 3D printing based auxetic cardiac patch with hiPSC-CMs for heart repair[J]. J Cardiovasc Dev Dis, 2021, 8(12):172. doi: 10.3390/jcdd8120172.
37
Wu Y, Wang L, Guo B, et al. Interwoven aligned conductive nanofiber yarn/hydrogel composite scaffolds for engineered 3D cardiac anisotropy[J]. ACS Nano, 2017, 11(6):5646-5659.
38
Tan Y, Richards D, Xu R, et al. Silicon nanowire-induced maturation of cardiomyocytes derived from human induced pluripotent stem cells[J]. Nano Lett, 2015, 15(5):2765-2772.
39
Richards DJ, Tan Y, Coyle R, et al. Nanowires and electrical stimulation synergistically improve functions of hiPSC cardiac spheroids[J]. Nano Lett, 2016, 16(7):4670-4678.
40
Baei P, Hosseini M, Baharvand H, et al. Electrically conductive materials for in vitro cardiac microtissue engineering[J]. J Biomed Mater Res A, 2020, 108(5):1203-1213.
41
Campostrini G, Windt LM, van Meer BJ, et al. Cardiac tissues from stem cells: new routes to maturation and cardiac regeneration[J]. Circ Res, 2021, 128(6):775-801.
42
Yu D, Wang X, Ye L. Cardiac tissue engineering for the treatment of myocardial infarction[J]. J Cardiovasc Dev Dis, 2021, 8(11):153. doi: 10.3390/jcdd8110153.
43
Majid QA, Fricker ATR, Gregory DA, et al. Natural biomaterials for cardiac tissue engineering: a highly biocompatible solution[J]. Front Cardiovasc Med, 2020, 7:554597. doi: 10.3389/fcvm.2020.554597.
44
Sharma V, Dash SK, Govarthanan K, et al. Recent advances in cardiac tissue engineering for the management of myocardium infarction[J]. Cells, 2021, 10(10):2538. doi: 10.3390/cells10102538.
45
Esmaeili H, Patino-Guerrero A, Hasany M, et al. Electroconductive biomaterials for cardiac tissue engineering[J]. Acta Biomater, 2022, 139:118-140.
46
Li J, Hu S, Zhu D, et al. All roads lead to rome (the heart): cell retention and outcomes from various delivery routes of cell therapy products to the heart[J]. J Am Heart Assoc, 2021, 10(8):e020402. doi: 10.1161/JAHA.120.020402.
47
Tabei R, Kawaguchi S, Kanazawa H, et al. Development of a transplant injection device for optimal distribution and retention of human induced pluripotent stem cellderivedcardiomyocytes[J]. J Heart Lung Transplant, 2019, 38(2):203-214.
48
Kawaguchi S, Soma Y, Nakajima K, et al. Intramyocardial transplantation of human iPS cell-derived cardiac spheroids improves cardiac function in heart failure animals[J]. JACC Basic Transl Sci, 2021, 6(3):239-254.
49
Sahito RGA, Sheng X, Maass M, et al. In vitro grown micro-tissues for cardiac cell replacement therapy in vivo[J]. Cell Physiol Biochem, 2019, 52(6):1309-1324.
50
Mitsutake Y, Pyun WB, Rouy D, et al. Improvement of local cell delivery using helix transendocardial delivery catheter in a porcine heart[J]. Int Heart J, 2017, 58(3):435-440.
51
Miyagawa S, Kainuma S, Kawamura T, et al. Transplantation of iPSC-derived cardiomyocyte patches for ischemic cardiomyopathy[J]. med Rxiv, 2022:21268295. DOI:10.1101/2021.12.27.21268295
52
Weinberger F, Breckwoldt K, Pecha S, et al. Cardiac repair in guinea pigs with human engineered heart tissue from induced pluripotent stem cells[J]. Sci Transl Med, 2016, 8(363):363ra148. doi: 10.1126/scitranslmed.aaf8781.
53
Gao L, Kupfer ME, Jung JP, et al. Myocardial tissue engineering with cells derived from human-induced pluripotent stem cells and a native-like, high-resolution, 3-dimensionally printed scaffold[J]. Circ Res, 2017, 120(8):1318-1325.
54
Munarin F, Kant RJ, Rupert CE, et al. Engineered human myocardium with local release of angiogenic proteins improves vascularization and cardiac function in injured rat hearts[J]. Biomaterials, 2020, 251:120033. doi: 10.1016/j.biomaterials.2020.120033.
55
Ye L, Chang YH, Xiong Q, et al. Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells[J]. Cell Stem Cell, 2014, 15(6):750-761.
56
Li J, Minami I, Shiozaki M, et al. Human pluripotent stem cell-derived cardiac tissue-like constructs for repairing the infarcted myocardium[J]. Stem Cell Reports, 2017, 9(5):1546-1559.
57
Noor N, Shapira A, Edri R, et al. 3D printing of personalized thick and perfusable cardiac patches and hearts[J]. Adv Sci (Weinh), 2019, 6(11):1900344. doi: 10.1002/advs.201900344.
58
van der Meer AD, Orlova VV, ten Dijke P, et al. Three-dimensional co-cultures of human endothelial cells and embryonic stem cell-derived pericytes inside a microfluidic device[J]. Lab Chip, 2013, 13(18):3562-3568.
59
Shen MJ. The cardiac autonomic nervous system: an introduction[J]. Herzschrittmacherther Elektrophysiol, 2021, 32(3):295-301.
60
Nicolas-Avila JA, Lechuga-Vieco AV, Esteban-Martinez L, et al. A network of macrophages supports mitochondrial homeostasis in the heart[J]. Cell, 2020, 183(1):94-109.e23.
61
Hulsmans M, Clauss S, Xiao L, et al. Macrophages facilitate electrical conduction in the heart[J]. Cell, 2017, 169(3):510-522.e20.
62
Li Y, Feng J, Song S, et al. gp130 controls cardiomyocyte proliferation and heart regeneration[J]. Circulation, 2020, 142(10):967-982.
63
Rusinkevich V, Huang Y, Chen ZY, et al. Temporal dynamics of immune response following prolonged myocardial ischemia/reperfusion with and without cyclosporine A[J]. ActaPharmacol Sin, 2019, 40(9):1168-1183.
64
Deuse T, Hu X, Gravina A, et al. Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients[J]. Nat Biotechnol, 2019, 37(3):252-258.
65
Deuse T, Tediashvili G, Hu X, et al. Hypoimmune induced pluripotent stem cell-derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice[J]. Proc Natl Acad Sci U S A, 2021, 118(28):e2022091118. doi: 10.1073/pnas.2022091118.
66
Buikema JW, Lee S, Goodyer WR, et al. Wnt activation and reduced cell-cell contact synergistically induce massive expansion of functional human iPSC-derived cardiomyocytes[J]. Cell Stem Cell, 2020, 27(1):50-63.e55.
67
Finklea FB, Tian Y, Kerscher P, et al. Engineered cardiac tissue microsphere production through direct differentiation of hydrogel-encapsulated human pluripotent stem cells[J]. Biomaterials, 2021, 274:120818. doi: 10.1016/j.biomaterials.2021.120818.
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