Tenascin‐C regulates migration of SOX10 tendon stem cells via integrin‐α9 for promoting patellar tendon remodeling

BioFactors ◽  
2021 ◽  
Author(s):  
Kang Xu ◽  
Yibo Shao ◽  
Yi Xia ◽  
Yuna Qian ◽  
Nan Jiang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Patellar Tendon ◽  
Tenascin C ◽  
Tendon Stem Cells ◽  
Tendon Remodeling

Evaluation of the Effect of Hyaluronic Acid–Based Biomaterial Enriched With Tenascin-C on the Behavior of the Neural Stem Cells

2021 ◽  
pp. 109158182110024
Author(s):  
Maryam Shahi ◽  
Daruosh Mohammadnejad ◽  
Mohammad Karimipour ◽  
Reza Rahbarghazi ◽  
Ali Abedelahi
Keyword(s):  
Stem Cells ◽  
Hyaluronic Acid ◽  
Neural Stem Cells ◽  
Mtt Assay ◽  
Dapi Staining ◽  
Biological Assays ◽  
Tenascin C ◽  
Electron Scanning Microscopy ◽  
Ethidium Bromide Staining ◽  
And Control

One of the most important natural extracellular constituents is hyaluronic acid (HA) with the potential to develop a highly organized microenvironment. In the present study, we enriched HA hydrogel with tenascin-C (TN-C) and examined the viability and survival of mouse neural stem cells (NSCs) using different biological assays. Following NSCs isolation and expansion, their phenotype was identified using flow cytometry analysis. Cell survival was measured using MTT assay and DAPI staining after exposure to various concentrations of 50, 100, 200, and 400 nM TN-C. Using acridine orange/ethidium bromide staining, we measured the number of live and necrotic cells after exposure to the combination of HA and TN-C. MTT assay revealed the highest NSCs viability rate in the group exposed to 100 nM TN-C compared to other groups, and a combination of 1% HA + 100 nM TN-C increased the viability of NSCs compared to the HA group after 24 hours. Electron scanning microscopy revealed the higher attachment of these cells to the HA + 100 nM TN-C substrate relative to the HA substrate. Epifluorescence imaging and DAPI staining of loaded cells on HA + 100 nM TN-C substrate significantly increased the number of NSCs per field over 72 hours compared to the HA group ( P < 0.05). Live and dead assay revealed that the number of live NSCs significantly increased in the HA + 100 TN-C group compared to HA and control groups. The enrichment of HA substrate with TN-C promoted viability and survival of NSCs and could be applied in neural tissue engineering approaches and regenerative medicine.

scholarly journals Intramuscular Injection of Botox Induces Tendon Atrophy and Senescence of Tendon-Derived Stem Cells

2020 ◽  
Author(s):  
Peilin Chen ◽  
Ziming Chen ◽  
Christopher Mitchell ◽  
Junjie Gao ◽  
Lianzhi Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mechanical Loading ◽  
Patellar Tendon ◽  
Intramuscular Injection ◽  
Vastus Lateralis ◽  
Collagen Fibre ◽  
Differentiation Capacity ◽  
Botox Injection

Abstract Background: Botulinum toxin (Botox) injection is in widespread clinical use for the treatment of muscle spasms and tendinopathy but the mechanism of action is poorly understood. Hypothesis: We hypothesised that the reduction of patellar-tendon mechanical-loading following intra-muscular injection of Botox results in tendon atrophy that is at least in part mediated by the induction of senescence of tendon-derived stem cells (TDSCs). Study Design: Controlled laboratory study Methods: A total of 36 mice were randomly divided in 2 groups (18 Botox-injected and 18 vehicle-only control). Mice were injected into to right vastus lateralis of quadriceps muscles either with Botox to induce mechanical stress deprivation of the patellar tendon or with normal saline as control. At 2 weeks post-injection, animals were euthanized prior to tissues harvest for either evaluation of tendon morphology or in vitro studies. TDSCs were isolated by cell-sorting prior to determination of viability, differentiation capacity and senescence markers, as well as assessing their response to mechanical loading in a bioreactor. Finally, to examine the mechanism of tendon atrophy in vitro, key proteins in the PTEN/AKT pathway were evaluated in TDSCs in both groups. Results: Two weeks after Botox injection, patellar tendons displayed atrophic features including tissue volume reduction and collagen fibre misalignment and increased degradation. The colony formation assay revealed the significantly reduced colony units of TDSCs in Botox injected group compared to controls. Multipotent differentiation capacity of TDSCs has also diminished after Botox injection. To examine if mechanical deprived TDSC is capable of forming tendon tissue, we used an isolated bioreactor system to culture 3D TDSCs constructs. The result showed that TDSCs from the Botox-treated group failed to restore tenogenic differentiation after appropriate mechanical loading. Examination of PTEN/AKT signalling pathway revealed that injection of Botox into quadriceps muscle causes PTEN/AKT mediated cell senescence of TDSCs. Conclusion: Intramuscular injection of Botox interferes with tendon homeostasis by inducing tendon atrophy and senescence of TDSCs. Botox injection may have long-term adverse consequences for the treatment of tendinopathy. Clinical relevance: Intramuscular Botox injection for tendinopathy and tendon injury could cause adverse effects in human tendons and re-evaluation of its long-term efficacy is warranted.

Tendon Stem Cells and Platelet-Rich Plasma for Repair of Injured Tendons

2011 ◽  
Author(s):  
James H-C. Wang
Keyword(s):  
Stem Cells ◽  
Sports Medicine ◽  
Platelet Rich Plasma ◽  
Normal Structure ◽  
Critical Issue ◽  
Tendon Injury ◽  
Tendon Injuries ◽  
Differentiation Potential ◽  
Tendon Stem Cells ◽  
Differential Properties

Tendon injuries, including acute tendon injuries and tendinopathy, are common in both occupational and athletic settings. However, current treatments for tendon injury are largely ineffective, as they cannot restore normal structure and function to injured tendons. This challenge mainly stems from our incomplete understanding of tendon cell properties and responses to biomechanical and biochemical environments surrounding the cells. In recent years, however, significant progress has been made on two fronts. First, tendon stem cells (TSCs) have been recently identified. The tendon-specific stem cells can self-renew and posses multi-differentiation potential and as such, may be used to repair injured tendons more effectively. Second, platelet-rich plasma (PRP) has now been widely used in orthopaedics and sports medicine to treat injured tendons. In this presentation, I will present data on TSCs, in terms of their differential properties with respect to tenocytes and their differential mechano-responses when subjected to small and large mechanical loading conditions. I will also discuss the basic scientific studies on PRP regarding its effects on TSCs, particularly on their differentiation, which is a critical issue related to the safety and efficacy of PRP treatment in clinics (Fig. 1).

Hypoxia promotes tenocyte differentiation of mesenchymal stem cells

2020 ◽  
Author(s):  
Guanyin Chen ◽  
wangqian zhang ◽  
Jintao Gu ◽  
Yuan Gao ◽  
Lei He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Patellar Tendon ◽  
Tendon Repair ◽  
Clinical Results ◽  
Tendon Injury ◽  
Tenogenic Differentiation ◽  
Tgf Β1

Abstract Background: Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cells (MSCs) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to investigate the role of hypoxia in the tenogenic differentiation of MSCs in vitro and in vivo and to compare the tenogenic differentiation capacities of different MSCs under hypoxia condition in vitro. Methods: Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized by the expression of MSC-specific markers and tri-lineage differentiation. The expression of hypoxia induced factor-1 alpha (Hif-1α) and the proliferation of AMSCs and BMSCs were examined in order to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia and/or Tgf-β1 condition. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Results: Hypoxia remarkably increased the expression of Hif-1α and the proliferation of AMSCs and BMSCs. Our in vitro results detected that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group, but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than those of normoxic BMSCs, as evidenced by histological scores, quantitative analysis of immunohistochemical staining for Col-1a1 and Tnmd, the range and average of collagen fibril diameters and patellar tendon biomechanical tests. Conclusions: These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.

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