Mesenchymal stem cells and macrophages and their interactions in tendon-bone healing

Chen, Zhuo; Jin, Ming; He, Hongyi; Dong, Jiabao; Li, Jing; Nie, Jiangbo; Wang, Zichen; Xu, Jianbin; Wu, Fengfeng

doi:10.1016/j.jot.2022.12.005

Cited by 35 publications

(10 citation statements)

References 126 publications

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“…Therefore, in combination with in vitro experiment results, it could be hypothesized that this excellent repair effect may be attributed to the immunomodulatory function and bidirectional bioactivities of multicellular scaffolds based on MS nanoparticles. On the one hand, a growing number of reports have identified excessive inflammation response as a cause for the regeneration of disorganized scar structures at the tendon-to-bone interface ( 5 , 28 , 59 ). The researchers found that there were more M2 macrophages and less M1 macrophages at the well-healed tendon-to-bone interface ( 22 ).…”

Section: Resultsmentioning

confidence: 99%

Immunomodulatory multicellular scaffolds for tendon-to-bone regeneration

Du,

Wu,

Han

et al. 2024

Sci. Adv.

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Limited motor activity due to the loss of natural structure impedes recovery in patients suffering from tendon-to-bone injury. Conventional biomaterials focus on strengthening the regenerative ability of tendons/bones to restore natural structure. However, owing to ignoring the immune environment and lack of multi-tissue regenerative function, satisfactory outcomes remain elusive. Here, combined manganese silicate (MS) nanoparticles with tendon/bone-related cells, the immunomodulatory multicellular scaffolds were fabricated for integrated regeneration of tendon-to-bone. Notably, by integrating biomimetic cellular distribution and MS nanoparticles, the multicellular scaffolds exhibited diverse bioactivities. Moreover, MS nanoparticles enhanced the specific differentiation of multicellular scaffolds via regulating macrophages, which was mainly attributed to the secretion of PGE2 in macrophages induced by Mn ions. Furthermore, three animal results indicated that the scaffolds achieved immunomodulation, integrated regeneration, and function recovery at tendon-to-bone interfaces. Thus, the multicellular scaffolds based on inorganic biomaterials offer an innovative concept for immunomodulation and integrated regeneration of soft/hard tissue interfaces.

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Section: Resultsmentioning

confidence: 99%

Immunomodulatory multicellular scaffolds for tendon-to-bone regeneration

Du,

Wu,

Han

et al. 2024

Sci. Adv.

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“…Recent studies have identified exosomes as an important mechanism of action for MSCs to promote tendon recovery ( 60 ). Interactions between MSCs and macrophages also promote rational healing of BTIs ( 61 ). Cell Sheet Technology, which preserves the intercellular junctions and extracellular matrix intact, in combination with MSCs, is not a new means of treating BTI injury ( 62 ).…”

Section: Discussionmentioning

confidence: 99%

Hot spots and frontiers in bone-tendon interface research: a bibliometric analysis and visualization from 2000 to 2023

Xiao,

Wen,

Yan

et al. 2024

Front. Surg.

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ObjectiveIn this research, we investigated the current status, hotspots, frontiers, and trends of research in the field of bone-tendon interface (BTI) from 2000 to 2023, based on bibliometrics and visualization and analysis in CiteSpace, VOSviewer, and a bibliometric package in R software.MethodsWe collected and organized the papers in the Web of Science core collection (WoSCC) for the past 23 years (2000–2023), and extracted and analyzed the papers related to BTI. The extracted papers were bibliometrically analyzed using CiteSpace for overall publication trends, authors, countries/regions, journals, keywords, research hotspots, and frontiers.ResultsA total of 1,995 papers met the inclusion criteria. The number of papers published and the number of citations in the field of BTI have continued to grow steadily over the past 23 years. In terms of research contribution, the United States leads in terms of the number and quality of publications, number of citations, and collaborations with other countries, while the United Kingdom and the Netherlands lead in terms of the average number of citations. The University of Leeds publishes the largest number of papers, and among the institutions hosting the 100 most cited papers Hospital for Special Surgery takes the top spot. MCGONAGLE D has published the highest number of papers (73) in the last 10 years. The top three clusters include #0 “psoriatic arthritis”, #1 “rotator cuff repair”, and #2 “tissue engineering”. The structure and function of the BTI and its key mechanisms in the healing process are the key to research, while new therapies such as mechanical stimulation, platelet-rich plasma, mesenchymal stem cells, and biological scaffolds are hot topics and trends in research.ConclusionOver the past 23 years, global research on the BTI has expanded in both breadth and depth. The focus of research has shifted from studies concentrating on the structure of the BTI and the disease itself to new therapies such as biomaterial-based alternative treatments, mechanical stimulation, platelet-rich plasma, etc.

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“…M2 macrophages accumulate later and play an anti-in ammatory role by releasing IL-10 and TGF-β (26). Previous studies have found that MSCs can regulate the in ammatory response by inhibiting the pro-M1 phenotype and promoting the M2 phenotype polarization of macrophages (29,30). In addition, matrix synthesis and degradation in normal tendons are in a dynamic balance regulated by MMP and TIMP.…”

Section: Discussionmentioning

confidence: 99%

Early transplantation of human umbilical cord mesenchymal stem cells is more effective in treating Achilles tendinopathy in a rat model

Yuan,

Yu,

Wang

et al. 2023

Preprint

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Objective Tendinopathy often causes pain and dysfunction that are difficult to treat. Various studies have examined the use of mesenchymal stem cells in treating tendinopathy, but the therapeutic effects differ depending on the dose and stage of tendinopathy. This study aims to investigate the efficacy and optimal delivery time of human umbilical cord mesenchymal stem cells (Huc-MSCs) in treating Achilles tendinopathy. Methods Tendinopathy was induced in SD rats by injecting 50 μL of collagenase I solutioninto the Achilles tendon. Tendinopathy was established after one week for early-stage models and after four weeks for advanced-stage models. The early tendinopathy models were randomly divided into the MSC-1 and control-1 groups, whereas the advanced tendinopathy models were randomly divided into the MSC-2 and control-2 groups. The rats were injected with 50 μL of Huc-MSCs solution or normal saline into the tendon twice. Achilles tendons were sampled at four weeks after treatment for related evaluation. Results H&E staining revealed lower histological scores in the MSC groups compared to the control groups, with the MSC-1 group scoring slightly lower than the MSC-2 group. Alizarin red staining showed lower heterotopic ossification in the MSC groups than in the control groups. RT-qPCR showed lower mRNA expression of TNF-α, IL-1β and MMP-3 in the MSC groups compared to the control groups. Immunohistochemical staining showed that early MSC delivery promoted collagen I and TIMP-3 synthesis and decreased MMP-3 expression. Transmission electron microscopy revealed larger collagen fiber diameter in the MSC groups, with the MSC-1 group yielding larger collagen fiber than the MSC-2 group. Biomechanical results showed higher failure load and stiffness in the MSC-1 group compared to the MSC-2 group. Conclusion Local injection of Huc-MSCs into the Achilles tendon restores normal collagen fiber arrangement, promotes matrix synthesis, reduces inflammation and improves biomechanical properties of the injured Achilles tendon. Results showed that early delivery is more effective than advanced delivery.

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Mesenchymal stem cells and macrophages and their interactions in tendon-bone healing

Cited by 35 publications

References 126 publications

Immunomodulatory multicellular scaffolds for tendon-to-bone regeneration

Immunomodulatory multicellular scaffolds for tendon-to-bone regeneration

Hot spots and frontiers in bone-tendon interface research: a bibliometric analysis and visualization from 2000 to 2023

Early transplantation of human umbilical cord mesenchymal stem cells is more effective in treating Achilles tendinopathy in a rat model

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