Exosomes Derived from Bone Marrow Stromal Cells (BMSCs) Enhance Tendon-Bone Healing by Regulating Macrophage Polarization

Shi, Youxing; Kang, Xin; Wang, Yunjiao; Bian, Xuting; He, Gang; Zhou, Mei; Tang, Kanglai

doi:10.12659/msm.923328

Cited by 73 publications

(117 citation statements)

References 35 publications

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“…After de-duplication, 247 studies were identified for title and abstract screening, of which 17 full-text studies were reviewed. Nine studies were eligible for data synthesis [25][26][27][28][29][30][31][32][33]. Searching references of the included studies, as well as studies that cited any of the included studies, yielded two more studies [34,35], giving a total of 11 studies for qualitative synthesis.…”

Section: Resultsmentioning

confidence: 99%

“…Another, less common method was trilineage differentiation into adipocytes, osteoblasts, and chondrocytes, seen in four studies involving 140 subjects [27,29,32,34]. The two most common methods for characterising MSCs were surface-maker expression using flow cytometry (used in seven studies with 310 subjects [25][26][27][28][29]32,34]), and testing for the absence of haematopoietic surface markers CD34 and CD45 (used in five studies involving 226 subjects [25,28,29,32,34]). Another, less common method was trilineage differentiation into adipocytes, osteoblasts, and chondrocytes, seen in four studies involving 140 subjects [27,29,32,34].…”

Section: Characterisation Of Mscsmentioning

confidence: 99%

“…The rationale was that hydroxycamptothecin elicits endoplasmic reticulum (ER) stress in MSCs, leading to increased ER stress effector proteins in secreted EVs, which increases the ability for EVs to prevent myofibroblast transformation and hence tendon adhesion [33]. The most widespread method of visualising EVs was using transmission electron microscopy (TEM) (used in nine studies involving 372 subjects [25][26][27][28][31][32][33][34][35]), and of those, three studies involving 105 subjects used the method to also measure EV dimensions [32][33][34]. Other methods of visualising EVs included atomic force microscopy (ATM), used in one study involving 16 subjects [29], and an 80kV electron microscope [30].…”

Section: Characterisation Of Evsmentioning

confidence: 99%

See 2 more Smart Citations

Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tendon and Ligament Repair—A Systematic Review of In Vivo Studies

Tennyson

Zhang

et al. 2021

Cells

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Tendon and ligament injury poses an increasingly large burden to society. This systematic review explores whether mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) can facilitate tendon/ligament repair in vivo. On 26 May 2021, a systematic search was performed on PubMed, Web of Science, Cochrane Library, Embase, to identify all studies that utilised MSC-EVs for tendon/ligament healing. Studies administering EVs isolated from human or animal-derived MSCs into in vivo models of tendon/ligament injury were included. In vitro, ex vivo, and in silico studies were excluded, and studies without a control group were excluded. Out of 383 studies identified, 11 met the inclusion criteria. Data on isolation, the characterisation of MSCs and EVs, and the in vivo findings in in vivo models were extracted. All included studies reported better tendon/ligament repair following MSC-EV treatment, but not all found improvements in every parameter measured. Biomechanics, an important index for tendon/ligament repair, was reported by only eight studies, from which evidence linking biomechanical alterations to functional improvement was weak. Nevertheless, the studies in this review showcased the safety and efficacy of MSC-EV therapy for tendon/ligament healing, by attenuating the initial inflammatory response and accelerating tendon matrix regeneration, providing a basis for potential clinical use in tendon/ligament repair.

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Section: Resultsmentioning

confidence: 99%

Section: Characterisation Of Mscsmentioning

confidence: 99%

Section: Characterisation Of Evsmentioning

confidence: 99%

See 1 more Smart Citation

Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tendon and Ligament Repair—A Systematic Review of In Vivo Studies

Tennyson

Zhang

et al. 2021

Cells

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“…Shi et al [ 36 ] demonstrated that EVs regulate BMSCs toward tenogenic differentiation, attenuate inflammation by increasing the expression of anti-inflammatory mediators, and enhance tendon healing in a patellar tendon injury model. Furthermore, EV delivery could increase M2 macrophage polarization and decrease M1 macrophage population as well as proinflammatory factors in the early phase of mouse Achilles tendon-bone reconstruction, improving tendon-bone healing [ 37 ]. The upregulated expression of MCP1 in our study indicated higher inflammation within the tendon-bone interface in the early stage after BM cell injection.…”

Section: Discussionmentioning

confidence: 99%

Effect of Freshly Isolated Bone Marrow Mononuclear Cells and Cultured Bone Marrow Stromal Cells in Graft Cell Repopulation and Tendon-Bone Healing after Allograft Anterior Cruciate Ligament Reconstruction

Huang

et al. 2021

IJMS

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Graft cell repopulation and tendon-bone tunnel healing are important after allograft anterior cruciate ligament reconstruction (ACLR). Freshly isolated bone marrow mononuclear cells (BMMNCs) have the advantage of short isolation time during surgery and may enhance tissue regeneration. Thus, we hypothesized that the effect of intra-articular BMMNCs in post-allograft ACLR treatment is comparable to that of cultured bone marrow stromal cells (BMSCs). A rabbit model of hamstring allograft ACLR was used in this study. Animals were randomly assigned to the BMMNC, BMSC, and control groups. Fresh BMMNCs isolated from the iliac crest during surgery and cultured BMSCs at passage four were used in this study. A total of 1 × 107 BMMNCs or BMSCs in 100 µL phosphate-buffered saline were injected into the knee joint immediately after ACLR. The control group was not injected with cells. At two and six weeks post operation, we assessed graft cell repopulation with histological and cell tracking staining (PKH26), and tendon-bone healing with histological micro-computed tomography and immunohistochemical analyses for collagen I and monocyte chemoattractant protein-1 (MCP1). At two weeks post operation, there was no significant difference in the total cell population within the allograft among the three groups. However, the control group showed significantly higher cell population within the allograft than that of BM cell groups at six weeks. Histological examination of proximal tibia revealed that the intra-articular delivered cells infiltrated into the tendon-bone interface. Compared to the control group, the BM cell groups showed broader gaps with interfacial fibrocartilage healing, similar collagen I level, and higher MCP1 expression in the early stage. Micro-CT did not reveal any significant difference among the three groups. BMMNCs and BMSCs had comparable effects on cell repopulation and interfacial allograft-bone healing. Intra-articular BM cells delivery had limited benefits on graft cell repopulation and caused higher inflammation than that in the control group in the early stage, with fibrocartilage formation in the tendon-bone interface after allograft ACLR.

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“…But in the process of tendon-bone healing, there is a lack of research on the mechanism of exosomes. In 2020, Shi et al [ 70 ] investigated the effects of BMSC-derived exosomes (BMSC-Exos) on tendon-bone healing. In the BMSC-Exos group, more fibrocartilage, higher maximum force, higher intensity, higher elastic modulus, higher M2 macrophage numbers, and more anti-inflammatory and chondrogenic factors were observed.…”

Section: Bmscsmentioning

confidence: 99%

Stem cell therapies in tendon-bone healing

Zhang

Wang

et al. 2021

WJSC

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Tendon-bone insertion injuries such as rotator cuff and anterior cruciate ligament injuries are currently highly common and severe. The key method of treating this kind of injury is the reconstruction operation. The success of this reconstructive process depends on the ability of the graft to incorporate into the bone. Recently, there has been substantial discussion about how to enhance the integration of tendon and bone through biological methods. Stem cells like bone marrow mesenchymal stem cells (MSCs), tendon stem/progenitor cells, synovium-derived MSCs, adipose-derived stem cells, or periosteum-derived periosteal stem cells can self-regenerate and potentially differentiate into different cell types, which have been widely used in tissue repair and regeneration. Thus, we concentrate in this review on the current circumstances of tendon-bone healing using stem cell therapy.

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Exosomes Derived from Bone Marrow Stromal Cells (BMSCs) Enhance Tendon-Bone Healing by Regulating Macrophage Polarization

Cited by 73 publications

References 35 publications

Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tendon and Ligament Repair—A Systematic Review of In Vivo Studies

Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tendon and Ligament Repair—A Systematic Review of In Vivo Studies

Effect of Freshly Isolated Bone Marrow Mononuclear Cells and Cultured Bone Marrow Stromal Cells in Graft Cell Repopulation and Tendon-Bone Healing after Allograft Anterior Cruciate Ligament Reconstruction

Stem cell therapies in tendon-bone healing

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