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间质干细胞用于心脏再生:从分化到细胞递送。

Mesenchymal Stem Cells for Cardiac Regeneration: from Differentiation to Cell Delivery.

机构信息

Stem Cell and Molecular Biology Laboratory, Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology-Madras, Chennai, Tamil Nadu, 600036, India.

出版信息

Stem Cell Rev Rep. 2021 Oct;17(5):1666-1694. doi: 10.1007/s12015-021-10168-0. Epub 2021 May 5.

DOI:10.1007/s12015-021-10168-0
PMID:33954876
Abstract

Mesenchymal stem cells (MSCs) are so far the most widely researched stem cells in clinics and used as an experimental cellular therapy module, particularly in cardiac regeneration and repair. Ever since the discovery of cardiomyogenesis induction in MSCs, a wide variety of differentiation protocols have been extensively used in preclinical models. However, pre differentiated MSC-derived cardiomyocytes have not been used in clinical trials; highlighting discrepancies and limitations in its use as a source of derived cardiomyocytes for transplantation to improve the damaged heart function. Therefore, this review article focuses on the strategies used to derive cardiomyocytes-like cells from MSCs isolated from three widely used tissue sources and their differentiation efficiencies. We have further discussed the role of MSCs in inducing angiogenesis as a cellular precursor to endothelial cells and its secretory aspects including exosomes. We have then discussed the strategies used for delivering cells in the damaged heart and how its retention plays a critical role in the overall outcome of the therapy. We have also conversed about the scope of the local and systemic modes of delivery of MSCs and the application of biomaterials to improve the overall delivery efficacy and function. We have finally discussed the advantages and limitations of cell delivery to the heart and the future scope of MSCs in cardiac regenerative therapy.

摘要

间充质干细胞(MSCs)是目前临床研究最广泛的干细胞,被用作实验性细胞治疗模块,特别是在心梗再生和修复方面。自从在 MSCs 中发现心肌发生诱导以来,已经广泛使用了各种分化方案来进行临床前模型研究。然而,预分化的 MSC 衍生的心肌细胞尚未在临床试验中使用;这突出了其作为用于移植以改善受损心脏功能的衍生心肌细胞来源的应用存在差异和局限性。因此,这篇综述文章重点介绍了从三种广泛使用的组织来源中分离的 MSCs 中诱导产生类心肌细胞的策略及其分化效率。我们进一步讨论了 MSCs 在诱导作为内皮细胞前体细胞的血管生成中的作用及其分泌方面,包括外泌体。然后,我们讨论了在受损心脏中输送细胞的策略以及其保留在治疗整体结果中的关键作用。我们还讨论了 MSCs 的局部和全身输送方式的范围以及生物材料的应用,以提高整体输送效率和功能。最后,我们讨论了细胞向心脏输送的优点和局限性,以及 MSCs 在心脏再生治疗中的未来前景。

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Mesenchymal Stem Cells for Cardiac Regeneration: from Differentiation to Cell Delivery.间质干细胞用于心脏再生:从分化到细胞递送。
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2
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MicroRNAs as a Novel Player for Differentiation of Mesenchymal Stem Cells into Cardiomyocytes.微小 RNA 作为一种新型分子在骨髓间充质干细胞向心肌细胞分化中的作用
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Small molecule 2'-deoxycytidine differentiates human umbilical cord-derived MSCs into cardiac progenitors in vitro and their in vivo xeno-transplantation improves cardiac function.小分子 2'-脱氧胞苷在体外将人脐带间充质干细胞分化为心脏祖细胞,其异种移植在体内改善心脏功能。
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引用本文的文献

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Current status and new horizons in stem cell therapy in cardiovascular regenerative medicine (CaVaReM): an update.心血管再生医学(CaVaReM)中干细胞治疗的现状与新视野:最新进展
Eur J Med Res. 2025 Sep 3;30(1):837. doi: 10.1186/s40001-025-03018-z.
2
Stem Cell Therapy in Ischemic Heart Failure.缺血性心力衰竭的干细胞治疗
Am J Cardiovasc Drugs. 2025 Jun 27. doi: 10.1007/s40256-025-00741-0.
3
The effects of Klotho delivering mesenchymal stem cell-derived small extracellular vesicles on acute kidney injury.递送间充质干细胞来源的小细胞外囊泡的Klotho对急性肾损伤的影响。

本文引用的文献

1
Shattering barriers toward clinically meaningful MSC therapies.打破临床意义上 MSC 疗法的障碍。
Sci Adv. 2020 Jul 22;6(30):eaba6884. doi: 10.1126/sciadv.aba6884. eCollection 2020 Jul.
2
Small molecule 2'-deoxycytidine differentiates human umbilical cord-derived MSCs into cardiac progenitors in vitro and their in vivo xeno-transplantation improves cardiac function.小分子 2'-脱氧胞苷在体外将人脐带间充质干细胞分化为心脏祖细胞,其异种移植在体内改善心脏功能。
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Key Success Factors for Regenerative Medicine in Acquired Heart Diseases.
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Current state of heart failure treatment: are mesenchymal stem cells and their exosomes a future therapy?心力衰竭治疗的现状:间充质干细胞及其外泌体是未来的治疗方法吗?
Front Cardiovasc Med. 2025 Apr 28;12:1518036. doi: 10.3389/fcvm.2025.1518036. eCollection 2025.
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The effect of blue and green light on human umbilical cord mesenchymal stem cells for promoting proliferation and wound healing.蓝光和绿光对人脐带间充质干细胞促进增殖及伤口愈合的作用。
Sci Rep. 2025 Apr 28;15(1):14787. doi: 10.1038/s41598-025-99083-9.
6
The Differentiation and Regeneration Potential of ABCB5 Mesenchymal Stem Cells: A Review and Clinical Perspectives.ABCB5间充质干细胞的分化与再生潜能:综述与临床展望
J Clin Med. 2025 Jan 21;14(3):660. doi: 10.3390/jcm14030660.
7
Optimizing Cardiomyocyte Differentiation: Comparative Analysis of Bone Marrow and Adipose-Derived Mesenchymal Stem Cells in Rats Using 5-Azacytidine and Low-Dose FGF and IGF Treatment.优化心肌细胞分化:使用5-氮杂胞苷以及低剂量成纤维细胞生长因子和胰岛素样生长因子处理对大鼠骨髓间充质干细胞和脂肪来源间充质干细胞的比较分析
Biomedicines. 2024 Aug 22;12(8):1923. doi: 10.3390/biomedicines12081923.
8
The Use of Hematopoietic Stem Cells for Heart Failure: A Systematic Review.造血干细胞治疗心力衰竭的系统评价。
Int J Mol Sci. 2024 Jun 17;25(12):6634. doi: 10.3390/ijms25126634.
9
Differentiation of mesenchymal stem cells into vascular endothelial cells in 3D culture: a mini review.三维培养中骨髓间充质干细胞向血管内皮细胞的分化:小型综述。
Mol Biol Rep. 2024 Jun 24;51(1):781. doi: 10.1007/s11033-024-09743-8.
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Research hotspots and emerging trends of mesenchymal stem cells in cardiovascular diseases: a bibliometric-based visual analysis.间充质干细胞在心血管疾病中的研究热点与新趋势:基于文献计量学的可视化分析
Front Cardiovasc Med. 2024 May 30;11:1394453. doi: 10.3389/fcvm.2024.1394453. eCollection 2024.
获得性心脏病再生医学的关键成功因素。
Stem Cell Rev Rep. 2020 Jun;16(3):441-458. doi: 10.1007/s12015-020-09961-0.
4
Glycogen synthase kinase 3β inhibitor- CHIR 99021 augments the differentiation potential of mesenchymal stem cells.糖原合酶激酶 3β抑制剂 CHIR99021 增强间充质干细胞的分化潜能。
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DNA methylation microarray uncovers a permissive methylome for cardiomyocyte differentiation in human mesenchymal stem cells.DNA 甲基化微阵列揭示了人类间充质干细胞中有利于心肌细胞分化的可塑甲基组。
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Adipose tissue derived mesenchymal stem cells are better respondents to TGFβ1 for in vitro generation of cardiomyocyte-like cells.脂肪组织来源的间充质干细胞对 TGFβ1 的反应更好,有利于体外生成类心肌细胞。
Mol Cell Biochem. 2019 Oct;460(1-2):53-66. doi: 10.1007/s11010-019-03570-3. Epub 2019 Jun 21.
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Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm.间充质干/基质细胞来源的外泌体:一种新的治疗模式。
Biomark Res. 2019 Apr 4;7:8. doi: 10.1186/s40364-019-0159-x. eCollection 2019.
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Sonic hedgehog promotes endothelial differentiation of bone marrow mesenchymal stem cells via VEGF-D.音猬因子通过血管内皮生长因子-D促进骨髓间充质干细胞向内皮细胞分化。
J Thorac Dis. 2018 Sep;10(9):5476-5488. doi: 10.21037/jtd.2018.09.50.
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Cardiomyogenic differentiation of human adipose-derived mesenchymal stem cells transduced with Tbx20-encoding lentiviral vectors.携带 Tbx20 编码慢病毒载体转染的人脂肪间充质干细胞的心肌生成分化。
J Cell Biochem. 2018 Jul;119(7):6146-6153. doi: 10.1002/jcb.26818. Epub 2018 Apr 10.
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Aspirin inhibits growth and enhances cardiomyocyte differentiation of bone marrow mesenchymal stem cells.阿司匹林抑制骨髓间充质干细胞的生长并增强其心肌细胞分化。
Eur J Pharmacol. 2018 May 15;827:198-207. doi: 10.1016/j.ejphar.2018.03.016. Epub 2018 Mar 15.