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肌腱组织工程:当前在优化人干细胞的肌腱向分化方案方面的进展。

Tendon tissue engineering: Current progress towards an optimized tenogenic differentiation protocol for human stem cells.

机构信息

Materials Science and Engineering, Monash University, 22 Alliance Lane, Clayton, VIC 3800, Australia.

Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.

出版信息

Acta Biomater. 2022 Jun;145:25-42. doi: 10.1016/j.actbio.2022.04.028. Epub 2022 Apr 22.


DOI:10.1016/j.actbio.2022.04.028
PMID:35470075
Abstract

Tendons are integral to our daily lives by allowing movement and locomotion but are frequently injured, leading to patient discomfort and impaired mobility. Current clinical procedures are unable to fully restore the native structure of the tendon, resulting in loss of full functionality, and the weakened tissue following repair often re-ruptures. Tendon tissue engineering, involving the combination of cells with biomaterial scaffolds to form new tendon tissue, holds promise to improve patient outcomes. A key requirement for efficacy in promoting tendon tissue formation is the optimal differentiation of the starting cell populations, most commonly adult tissue-derived mesenchymal stem/stromal cells (MSCs), into tenocytes, the predominant cellular component of tendon tissue. Currently, a lack of consensus on the protocols for effective tenogenic differentiation is hampering progress in tendon tissue engineering. In this review, we discuss the current state of knowledge regarding human stem cell differentiation towards tenocytes and tendon tissue formation. Tendon development and healing mechanisms are described, followed by a comprehensive overview of the current protocols for tenogenic differentiation, including the effects of biochemical and biophysical cues, and their combination, on tenogenesis. Lastly, a synthesis of the key features of these protocols is used to design future approaches. The holistic evaluation of current knowledge should facilitate and expedite the development of efficacious stem cell tenogenic differentiation protocols with future impact in tendon tissue engineering. STATEMENT OF SIGNIFICANCE: The lack of a widely-adopted tenogenic differentiation protocol has been a major hurdle in the tendon tissue engineering field. Building on current knowledge on tendon development and tendon healing, this review surveys peer-reviewed protocols to present a holistic evaluation and propose a pathway to facilitate and expedite the development of a consensus protocol for stem cell tenogenic differentiation and tendon tissue engineering.

摘要

肌腱使我们能够进行日常活动和运动,但它们经常受伤,导致患者不适和活动能力受损。目前的临床程序无法完全恢复肌腱的天然结构,导致功能丧失,修复后的组织往往会再次断裂。肌腱组织工程涉及将细胞与生物材料支架结合起来形成新的肌腱组织,有望改善患者的治疗效果。促进肌腱组织形成的关键要求是优化起始细胞群的分化,最常见的是成年组织来源的间充质干细胞(MSCs)分化为肌腱组织的主要细胞成分——肌腱细胞。目前,缺乏有效促进肌腱细胞分化的方案共识,阻碍了肌腱组织工程的进展。在这篇综述中,我们讨论了关于人类干细胞向肌腱细胞分化和肌腱组织形成的最新知识状态。描述了肌腱的发育和愈合机制,然后全面概述了目前的肌腱细胞分化方案,包括生化和生物物理线索及其组合对肌腱形成的影响。最后,综合这些方案的关键特征,设计未来的方法。全面评估现有知识应该有助于并加速开发有效的干细胞肌腱细胞分化方案,为肌腱组织工程的未来发展提供助力。

意义:缺乏广泛采用的肌腱细胞分化方案一直是肌腱组织工程领域的主要障碍。本综述以肌腱发育和肌腱愈合的现有知识为基础,调查了同行评议的方案,提出了一种全面评估方法,并提出了一种促进干细胞肌腱细胞分化和肌腱组织工程共识方案开发的途径。

相似文献

[1]
Tendon tissue engineering: Current progress towards an optimized tenogenic differentiation protocol for human stem cells.

Acta Biomater. 2022-6

[2]
Growth Differentiation Factor 5-Induced Mesenchymal Stromal Cells Enhance Tendon Healing.

Tissue Eng Part C Methods. 2024-10

[3]
Stepwise Differentiation of Mesenchymal Stem Cells Augments Tendon-Like Tissue Formation and Defect Repair In Vivo.

Stem Cells Transl Med. 2016-8

[4]
Mesenchymal Stem Cells Empowering Tendon Regenerative Therapies.

Int J Mol Sci. 2019-6-19

[5]
Growth Factor-Mediated Tenogenic Induction of Multipotent Mesenchymal Stromal Cells Is Altered by the Microenvironment of Tendon Matrix.

Cell Transplant. 2018-9-25

[6]
A systematic investigation of the effects of TGF-β3 and mechanical stimulation on tenogenic differentiation of mesenchymal stromal cells in a poly(ethylene glycol)/gelatin-based hydrogel.

J Orthop Translat. 2023-10-21

[7]
Tenogenic differentiation of stem cells for tendon repair-what is the current evidence?

J Tissue Eng Regen Med. 2011-5-5

[8]
Enhanced tenogenic differentiation and tendon-like tissue formation by Scleraxis overexpression in human amniotic mesenchymal stem cells.

J Mol Histol. 2020-6

[9]
CTGF induces tenogenic differentiation and proliferation of adipose-derived stromal cells.

J Orthop Res. 2019-2-28

[10]
Progress with stem cell therapies for tendon tissue regeneration.

Expert Opin Biol Ther. 2020-11

引用本文的文献

[1]
Mechanobiomaterials: Harnessing mechanobiology principles for tissue repair and regeneration.

Mechanobiol Med. 2024-5-16

[2]
Intelligent Manufacturing for Osteoarthritis Organoids.

Cell Prolif. 2025-4-26

[3]
Epigenetic mechanisms in stem cell therapies for achilles tendinopathy.

Front Cell Dev Biol. 2025-3-13

[4]
Biomaterial Properties and Differentiation Strategies for Tenogenic Differentiation of Mesenchymal Stem Cells.

Cells. 2025-3-18

[5]
3D bioprinted multi-layered cell constructs with gradient core-shell interface for tendon-to-bone tissue regeneration.

Bioact Mater. 2024-10-11

[6]
Therapeutic effects of chitosan/β-glycerophosphate/collagen hydrogel combined with MSCs on chronic achilles tendon injury via the Akt/GSK-3β pathway.

J Orthop Surg Res. 2025-2-26

[7]
Therapeutic potential and mechanisms of umbilical cord mesenchymal stem cells differentiating into tendon cells and promotion of rotator cuff tendon-bone healing.

J Tissue Eng. 2025-1-29

[8]
Skeletal organoids.

Biomater Transl. 2024-11-15

[9]
A CD26 tendon stem progenitor cell population contributes to tendon repair and heterotopic ossification.

Nat Commun. 2025-1-16

[10]
Regenerative properties of bone marrow mesenchymal stem cell derived exosomes in rotator cuff tears.

J Transl Med. 2025-1-12

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