scholarly journals Short Wave Enhances Mesenchymal Stem Cell Recruitment through Hypoxia-Inducible Factor-1 Signaling in Fracture Healing

2020 ◽  
Author(s):  
Dongmei Ye ◽  
Chen Chen ◽  
Qiwen Wang ◽  
Qi Zhang ◽  
Sha Li ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Fracture Healing ◽  
Callus Formation ◽  
Healing Process ◽  
Short Wave ◽  
Fracture Site ◽  
Femur Fractures

Abstract Background As a type of high-frequency electrotherapy, a short wave can promote the fracture healing process; yet, its underlying therapeutic mechanisms still remain unclear. Purpose To observe the effect of short wave on mesenchymal stem cell (MSC) homing and its mechanisms associated with fracture healing. Materials and Methods For in vivo study, the effect of Short-Wave therapy in relation to fracture healing was examined in stabilized femur fractures model of 40 SD rats. Radiography was used to analyze the morphology and micro-architecture of the callus. Additionally, fluorescence assays were used to analyze the GFP-labeled MSC homing after treatment in 20 nude mice with a femoral fracture. For in vitro study, osteoblast from newborn rats simulated fracture site was first irradiated by the Short-Wave; siRNA targeting HIF-1 was used to investigate the role of HIF-1. Osteoblast culture medium was then collected as chemotaxis content of MSC, and the migration of MSC from rats was evaluated using wound healing assay and trans-well chamber test. The expression of HIF-1 and its related factors were quantified by q RT-PCR, ELISA, and Western blot. Results Our in vivo experiment indicated that Short-Wave therapy could promote MSC migration, increase local and serum HIF-1 and SDF-1 levels, induce changes in callus formation, and improve callus microarchitecture and mechanical properties, thus speeding up the healing process of the fracture site. Moreover, the in vitro results further indicated that Short-Waves therapy upregulated HIF-1 and SDF-1 expression in osteoblast and in the medium, as well as the expression of CXCR-4, β-catenin, F-actin and phosphorylation levels of FAK in MSC. On the other hand, the inhibition of HIF-1α was significantly restrained by the inhibition of HIF-1α in osteoblast, and it partially inhibited the migration of MSC. Conclusions These results suggested that short wave could increase HIF-1 in callus, which is one of the crucial mechanisms of chemotaxis MSC homing in fracture healing.

scholarly journals Short Wave Enhances Mesenchymal Stem Cell Recruitment through Hypoxia-Inducible Factor-1 Signaling in Fracture Healing

2020 ◽  
Author(s):  
Dongmei Ye ◽  
Chen Chen ◽  
Qiwen Wang ◽  
Qi Zhang ◽  
Sha Li ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Fracture Healing ◽  
Callus Formation ◽  
Healing Process ◽  
Short Wave ◽  
Fracture Site ◽  
Related Factors ◽  
Femur Fractures

Abstract Background: As a type of high-frequency electrotherapy, a short wave can promote the fracture healing process; yet, its underlying therapeutic mechanisms still remain unclear.Purpose: To observe the effect of short wave on mesenchymal stem cell (MSC) homing and its mechanisms associated with fracture healing.Materials and Methods: The effect of short wave on a fracture healing was examined in 40 rats. Stabilized femur fractures were established by intramedullary fixation; radiography was used to analyze the morphology and micro-architecture of the callus. Additionally, fluorescence assays were used to analyze the MSC migration after treatment in 20 nude mice with a femoral fracture. For in vitro study, osteoblast simulated fracture site was first irradiated by the short wave; siRNA targeting HIF-1 was used to investigate the role of HIF-1. Osteoblast cultured supernatant was then collected as chemotaxis content of MSC, and the migration of MSC was evaluated using wound healing assay and trans-well chamber test. The expression of HIF-1 and its related factors were quantified by qRT-PCR, ELISA, and Western blot.Results: Our in vivo experiment indicated that short wave could promote MSC migration, increase local and serum HIF-1 levels, induce changes in callus formation, and improve callus microarchitecture and mechanical properties, thus speeding up the healing process of the fracture site. Moreover, the in vitro results further indicated that short waves upregulated HIF-1 expression in osteoblast and increased HIF-1, SDF-1 protein levels in the supernatant, as well as the expression of CXCR-4, β-catenin, F-actin and phosphorylation levels of FAK in MSC. On the other hand, the inhibition of HIF-1α was significantly restrained by the inhibition of HIF-1α in osteoblast and it partially inhibited the migration of MSC.Conclusions: These results suggested that short wave could increase HIF-1 in callus, which is one of the crucial mechanisms of chemotaxis MSC homing in fracture healing.

scholarly journals Short-wave enhances mesenchymal stem cell recruitment in fracture healing by increasing HIF-1 in callus

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Dongmei Ye ◽  
Chen Chen ◽  
Qiwen Wang ◽  
Qi Zhang ◽  
Sha Li ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Fracture Healing ◽  
Callus Formation ◽  
Healing Process ◽  
Short Wave ◽  
Fracture Site ◽  
Related Factors

Abstract Background As a type of high-frequency electrotherapy, a short-wave can promote the fracture healing process; yet, its underlying therapeutic mechanisms remain unclear. Purpose To observe the effect of Short-Wave therapy on mesenchymal stem cell (MSC) homing and relative mechanisms associated with fracture healing. Materials and methods For in vivo study, the effect of Short-Wave therapy to fracture healing was examined in a stabilized femur fracture model of 40 SD rats. Radiography was used to analyze the morphology and microarchitecture of the callus. Additionally, fluorescence assays were used to analyze the GFP-labeled MSC homing after treatment in 20 nude mice with a femoral fracture. For in vitro study, osteoblast from newborn rats simulated fracture site was first irradiated by the Short-Wave; siRNA targeting HIF-1 was used to investigate the role of HIF-1. Osteoblast culture medium was then collected as chemotaxis content of MSC, and the migration of MSC from rats was evaluated using wound healing assay and trans-well chamber test. The expression of HIF-1 and its related factors were quantified by q RT-PCR, ELISA, and Western blot. Results Our in vivo experiment indicated that Short-Wave therapy could promote MSC migration, increase local and serum HIF-1 and SDF-1 levels, induce changes in callus formation, and improve callus microarchitecture and mechanical properties, thus speeding up the healing process of the fracture site. Moreover, the in vitro results further indicated that Short-Wave therapy upregulated HIF-1 and SDF-1 expression in osteoblast and its cultured medium, as well as the expression of CXCR-4, β-catenin, F-actin, and phosphorylation levels of FAK in MSC. On the other hand, the inhibition of HIF-1α was significantly restrained by the inhibition of HIF-1α in osteoblast, and it partially inhibited the migration of MSC. Conclusions These results suggested that Short-Wave therapy could increase HIF-1 in callus, which is one of the crucial mechanisms of chemotaxis MSC homing in fracture healing.

scholarly journals Short Wave Enhances Mesenchymal Stem Cell Recruitment through Hypoxia-Inducible Factor-1 Signaling in Fracture Healing

2020 ◽  
Author(s):  
Dongmei Ye ◽  
Chen Chen ◽  
Qiwen Wang ◽  
Qi Zhang ◽  
Sha Li ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Fracture Healing ◽  
Callus Formation ◽  
Healing Process ◽  
Short Wave ◽  
Fracture Site ◽  
Related Factors ◽  
Femur Fractures

Abstract Background: As a type of high-frequency electrotherapy, a Short-Wave can promote the fracture healing process; yet, its underlying therapeutic mechanisms still remain unclear.Purpose: To observe the effect of Short-Wave therapy on mesenchymal stem cell (MSC) homing and relative mechanisms associated with fracture healing. Materials and Methods: The effect of Short-Wave therapy in relation to fracture healing was examined in 40 SD rats. Stabilized femur fractures were established by intramedullary fixation; radiography was used to analyze the morphology and micro-architecture of the callus. Additionally, fluorescence assays were used to analyze the MSC migration after treatment in 20 nude mice with a femoral fracture. For in vitro study, osteoblast simulated fracture site was first irradiated by the Short-Wave; siRNA targeting HIF-1 was used to investigate the role of HIF-1. Osteoblast culture medium was then collected as chemotaxis content of MSC, and the migration of MSC was evaluated using wound healing assay and trans-well chamber test. The expression of HIF-1 and its related factors were quantified by q RT-PCR, ELISA, and Western blot.Results: Our in vivo experiment indicated that Short-Wave therapy could promote MSC migration, increase local and serum HIF-1 and SDF-1 levels, induce changes in callus formation, and improve callus microarchitecture and mechanical properties, thus speeding up the healing process of the fracture site. Moreover, the in vitro results further indicated that Short-Waves therapy upregulated HIF-1 and SDF-1 expression in osteoblast and in the medium, as well as the expression of CXCR-4, β-catenin, F-actin and phosphorylation levels of FAK in MSC. On the other hand, the inhibition of HIF-1α was significantly restrained by the inhibition of HIF-1α in osteoblast, and it partially inhibited the migration of MSC.Conclusions: These results suggested that Short-Wave therapy could increase HIF-1 in callus, which is one of the crucial mechanisms of chemotaxis MSC homing in fracture healing.

scholarly journals Short-Wave Enhances Mesenchymal Stem Cells Recruitment in Fracture Healing by Increasing HIF-1 in Callus

2020 ◽  
Author(s):  
Dongmei Ye ◽  
Chen Chen ◽  
Qiwen Wang ◽  
Qi Zhang ◽  
Sha Li ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Callus Formation ◽  
Healing Process ◽  
Short Wave ◽  
Fracture Site ◽  
Related Factors ◽  
Femur Fractures ◽  
Osteoblast Culture

Abstract Background: As a type of high-frequency electrotherapy, a Short-Wave can promote the fracture healing process; yet, its underlying therapeutic mechanisms remain unclear.Purpose: To observe the effect of Short-Wave therapy on mesenchymal stem cell (MSC) homing and relative mechanisms associated with fracture healing. Materials and Methods: For in vivo study, the effect of Short-Wave therapy to fracture healing was examined in stabilized femur fractures model of 40 SD rats. Radiography was used to analyze the morphology and microarchitecture of the callus. Additionally, fluorescence assays were used to analyze the GFP-labeled MSC homing after treatment in 20 nude mice with a femoral fracture. For in vitro study, osteoblast from newborn rats simulated fracture site was first irradiated by the Short-Wave; siRNA targeting HIF-1 was used to investigate the role of HIF-1. Osteoblast culture medium was then collected as chemotaxis content of MSC, and the migration of MSC from rats was evaluated using wound healing assay and trans-well chamber test. The expression of HIF-1 and its related factors were quantified by q RT-PCR, ELISA, and Western blot.Results: Our in vivo experiment indicated that Short-Wave therapy could promote MSC migration, increase local and serum HIF-1 and SDF-1 levels, induce changes in callus formation, and improve callus microarchitecture and mechanical properties, thus speeding up the healing process of the fracture site. Moreover, the in vitro results further indicated that Short-Waves therapy upregulated HIF-1 and SDF-1 expression in osteoblast and its cultured medium, as well as the expression of CXCR-4, β-catenin, F-actin and phosphorylation levels of FAK in MSC. On the other hand, the inhibition of HIF-1α was significantly restrained by the inhibition of HIF-1α in osteoblast, and it partially inhibited the migration of MSC.Conclusions: These results suggested that Short-Wave therapy could increase HIF-1 in callus, which is one of the crucial mechanisms of chemotaxis MSC homing in fracture healing.

scholarly journals Short-Wave Enhances MSC Recruitment in Fracture Healing from Increasing HIF-1 in Callus

2020 ◽  
Author(s):  
Dongmei Ye ◽  
Chen Chen ◽  
Qiwen Wang ◽  
Qi Zhang ◽  
Sha Li ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Callus Formation ◽  
Healing Process ◽  
Short Wave ◽  
Fracture Site ◽  
Related Factors ◽  
Femur Fractures ◽  
Osteoblast Culture

Abstract Background: As a type of high-frequency electrotherapy, a Short-Wave can promote the fracture healing process; yet, its underlying therapeutic mechanisms still remain unclear.Purpose: To observe the effect of Short-Wave therapy on mesenchymal stem cell (MSC) homing and relative mechanisms associated with fracture healing. Materials and Methods: For in vivo study, the effect of Short-Wave therapy in relation to fracture healing was examined in stabilized femur fractures model of 40 SD rats. Radiography was used to analyze the morphology and micro-architecture of the callus. Additionally, fluorescence assays were used to analyze the GFP-labeled MSC homing after treatment in 20 nude mice with a femoral fracture. For in vitro study, osteoblast from newborn rats simulated fracture site was first irradiated by the Short-Wave; siRNA targeting HIF-1 was used to investigate the role of HIF-1. Osteoblast culture medium was then collected as chemotaxis content of MSC, and the migration of MSC from rats was evaluated using wound healing assay and trans-well chamber test. The expression of HIF-1 and its related factors were quantified by q RT-PCR, ELISA, and Western blot.Results: Our in vivo experiment indicated that Short-Wave therapy could promote MSC migration, increase local and serum HIF-1 and SDF-1 levels, induce changes in callus formation, and improve callus microarchitecture and mechanical properties, thus speeding up the healing process of the fracture site. Moreover, the in vitro results further indicated that Short-Waves therapy upregulated HIF-1 and SDF-1 expression in osteoblast and in the medium, as well as the expression of CXCR-4, β-catenin, F-actin and phosphorylation levels of FAK in MSC. On the other hand, the inhibition of HIF-1α was significantly restrained by the inhibition of HIF-1α in osteoblast, and it partially inhibited the migration of MSC.Conclusions: These results suggested that Short-Wave therapy could increase HIF-1 in callus, which is one of the crucial mechanisms of chemotaxis MSC homing in fracture healing.

scholarly journals The Lack of a Representative Tendinopathy Model Hampers Fundamental Mesenchymal Stem Cell Research

2021 ◽  
Vol 9 ◽  
Author(s):  
Marguerite Meeremans ◽  
Gerlinde R. Van de Walle ◽  
Sandra Van Vlierberghe ◽  
Catharina De Schauwer
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Healing Process ◽  
Cell Encapsulation ◽  
Vascular Supply ◽  
Tendon Injuries ◽  
Current Status ◽  
Uniaxial Stretching

Overuse tendon injuries are a major cause of musculoskeletal morbidity in both human and equine athletes, due to the cumulative degenerative damage. These injuries present significant challenges as the healing process often results in the formation of inferior scar tissue. The poor success with conventional therapy supports the need to search for novel treatments to restore functionality and regenerate tissue as close to native tendon as possible. Mesenchymal stem cell (MSC)-based strategies represent promising therapeutic tools for tendon repair in both human and veterinary medicine. The translation of tissue engineering strategies from basic research findings, however, into clinical use has been hampered by the limited understanding of the multifaceted MSC mechanisms of action. In vitro models serve as important biological tools to study cell behavior, bypassing the confounding factors associated with in vivo experiments. Controllable and reproducible in vitro conditions should be provided to study the MSC healing mechanisms in tendon injuries. Unfortunately, no physiologically representative tendinopathy models exist to date. A major shortcoming of most currently available in vitro tendon models is the lack of extracellular tendon matrix and vascular supply. These models often make use of synthetic biomaterials, which do not reflect the natural tendon composition. Alternatively, decellularized tendon has been applied, but it is challenging to obtain reproducible results due to its variable composition, less efficient cell seeding approaches and lack of cell encapsulation and vascularization. The current review will overview pros and cons associated with the use of different biomaterials and technologies enabling scaffold production. In addition, the characteristics of the ideal, state-of-the-art tendinopathy model will be discussed. Briefly, a representative in vitro tendinopathy model should be vascularized and mimic the hierarchical structure of the tendon matrix with elongated cells being organized in a parallel fashion and subjected to uniaxial stretching. Incorporation of mechanical stimulation, preferably uniaxial stretching may be a key element in order to obtain appropriate matrix alignment and create a pathophysiological model. Together, a thorough discussion on the current status and future directions for tendon models will enhance fundamental MSC research, accelerating translation of MSC therapies for tendon injuries from bench to bedside.

scholarly journals Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 730
Author(s):  
Biji Mathew ◽  
Leianne A. Torres ◽  
Lorea Gamboa Gamboa Acha ◽  
Sophie Tran ◽  
Alice Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Time Course ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Paracrine Effects

Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.

scholarly journals A novel MRI compatible mouse fracture model to characterize and monitor bone regeneration and tissue composition

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Nina Schmitz ◽  
Melanie Timmen ◽  
Katharina Kostka ◽  
Verena Hoerr ◽  
Christian Schwarz ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Regeneration ◽  
Cell Attachment ◽  
Healing Process ◽  
Living Organism ◽  
Fracture Site ◽  
Tissue Composition ◽  
Metal Implants ◽  
Callus Tissues

Abstract Over the last years, murine in vivo magnetic resonance imaging (MRI) contributed to a new understanding of tissue composition, regeneration and diseases. Due to artefacts generated by the currently used metal implants, MRI is limited in fracture healing research so far. In this study, we investigated a novel MRI-compatible, ceramic intramedullary fracture implant during bone regeneration in mice. Three-point-bending revealed a higher stiffness of the ceramic material compared to the metal implants. Electron microscopy displayed a rough surface of the ceramic implant that was comparable to standard metal devices and allowed cell attachment and growth of osteoblastic cells. MicroCT-imaging illustrated the development of the callus around the fracture site indicating a regular progressing healing process when using the novel implant. In MRI, different callus tissues and the implant could clearly be distinguished from each other without any artefacts. Monitoring fracture healing using MRI-compatible implants will improve our knowledge of callus tissue regeneration by 3D insights longitudinal in the same living organism, which might also help to reduce the consumption of animals for future fracture healing studies, significantly. Finally, this study may be translated into clinical application to improve our knowledge about human bone regeneration.

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